tag:theconversation.com,2011:/global/topics/antibiotic-resistance-6035/articlesAntibiotic resistance – The Conversation2024-02-22T13:42:50Ztag:theconversation.com,2011:article/2202832024-02-22T13:42:50Z2024-02-22T13:42:50ZBacteria can develop resistance to drugs they haven’t encountered before − scientists figured this out decades ago in a classic experiment<figure><img src="https://images.theconversation.com/files/575458/original/file-20240213-24-7w1h4o.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2048%2C1480&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria are evolutionarily primed to outpace drug developers.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/nihgov/28881401596/in/photolist-U4kMcq-c57xDd-L19JtW-c9uWe5-dYBMYW-a5tw3L-2joPCWz-2jfgs7P-9VPmA4-fuUV2g-fvxv6D-ot5Jyg-fvacBd-vughy5-7NapMs-7N7qSL-yrSV6f-7N5dpc-Mj3KFR-7Na6i5-ysPK3x-7Na5Wq-ftHb6n-ftXtfs-ftH7Vt-7Na6P5-tCCMPo-xvLN1S-ybiGai-yqtCoy-982F9z-ftHaAP-7N3qKg-7N674D-fvxufn-fvMDps-x2Btgv-ftHapZ-7Na6sy-7NaoHs-fuUUt8-fuUQjz-fvxptp-fuUXN2-7U2mNs-7N66b2-fvaabC-xtGans">National Institute of Allergy and Infectious Diseases, National Institutes of Health/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Do bacteria mutate randomly, or do they mutate for a purpose? Researchers have been <a href="https://doi.org/10.1017/S0022172400017125">puzzling over this conundrum for over a century</a>.</p>
<p>In 1943, microbiologist Salvador Luria and physicist turned biologist Max Delbrück <a href="https://doi.org/10.1080/09332480.2010.10739800">invented an experiment</a> to argue that bacteria mutated aimlessly. Using their test, other scientists showed that bacteria could acquire resistance to antibiotics they hadn’t encountered before.</p>
<p>The <a href="https://doi.org/10.1080/09332480.2010.10739800">Luria–Delbrück experiment</a> has had a significant effect on science. The findings helped Luria and Delbruck win the <a href="https://www.nobelprize.org/prizes/medicine/1969/summary/">Nobel Prize in physiology or medicine in 1969</a>, and students today learn this experiment in <a href="https://doi.org/10.1128/jmbe.00161-23">biology classrooms</a>. I have been studying this experiment in my work as a biostatistician for <a href="https://doi.org/10.1016/S0025-5564(99)00045-0">over 20 years</a>.</p>
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<p>Decades later, this experiment offers lessons still relevant today, because it implies that bacteria can develop resistance to antibiotics that haven’t been developed yet.</p>
<h2>Slot machines and a eureka moment</h2>
<p>Imagine a test tube containing bacteria living in nutrient broth. The broth is cloudy due to the high concentration of bacteria within it. Adding a virus that infects bacteria, <a href="https://theconversation.com/viruses-are-both-the-villains-and-heroes-of-life-as-we-know-it-169131">also known as a phage</a>, into the tube kills most of the bacteria and makes the broth clear.</p>
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<a href="https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of bacteriophage structure." src="https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=1014&fit=crop&dpr=1 600w, https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=1014&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=1014&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1274&fit=crop&dpr=1 754w, https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1274&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/426550/original/file-20211014-27-n6jugx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1274&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Bacteriophages are viruses that specifically infect bacteria.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/flat-illustration-of-bacteriophage-royalty-free-illustration/1285360925">Kristina Dukart/iStock via Getty Images Plus</a></span>
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<p>However, keeping the test tube under conditions favorable for bacterial growth will turn the broth cloudy again over time. This indicates that the bacteria developed resistance against the phages and were able to proliferate.</p>
<p>What role did the phages play in this change?</p>
<p>Some scientists thought the phages incited the bacteria to mutate for survival. Others suggested that bacteria routinely mutate randomly, and the development of phage-resistant variants was simply <a href="https://doi.org/10.1128/jb.28.6.619-639.1934">a lucky outcome</a>. Luria and Delbrück had been working together for months to solve this conundrum, but none of their experiments had been successful. </p>
<p>On the night of Jan. 16, 1943, Luria got a hint about how to crack the mystery while watching a colleague hit the jackpot at a slot machine. The next morning, he hurried to his lab.</p>
<p>Luria’s experiment consisted of a few tubes and dishes. Each tube contained nutrient broth that would help the bacteria <em>E. coli</em> multiply, while each dish contained material coated with phages. A few bacteria were placed into each tube and given two opportunities to generate phage-resistant variants. They could either mutate in the tubes in the absence of phages, or they could mutate in the dishes in the presence of phages.</p>
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<a href="https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of six test tubes and and six petri dishes, a few of the dishes containing red dots" src="https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=277&fit=crop&dpr=1 600w, https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=277&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=277&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=348&fit=crop&dpr=1 754w, https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=348&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/575442/original/file-20240213-28-9m0ay7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=348&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">This diagram of the Luria-Delbrück experiment depicts colonies of phage-resistant variants of <em>E. coli</em> (red) developing in petri dishes.</span>
<span class="attribution"><span class="source">Qi Zheng</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>The next day, Luria transferred the bacteria in each tube into a dish filled with phages. The day after that, he counted the number of resistant bacterial colonies in each dish. </p>
<p>If bacteria develop resistance against phages by interacting with them, none of the bacteria in the tubes should have mutations. On the other hand, only a few of the bacteria – say, 1 out of 10 million bacteria – should spawn resistant variants when they are transferred into a dish containing phages. Each phage-resistant variant would grow into a colony, but the remaining bacteria would die from infection.</p>
<p>If bacteria develop resistance independently of interacting with phages, some of the bacteria in the tubes will have mutations. This is because each time a bacterium divides in a tube, it has a small probability of spawning a resistant variant. If the starting generation of bacteria is the first to mutate, at least half of the bacteria will be resistant in later generations. If a bacterium in the second generation is the first to mutate, at least an eighth of the bacteria will be resistant in later generations.</p>
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<a href="https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Four tree diagrams of green and red circles, with subsequent branches from red dots turning red" src="https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=340&fit=crop&dpr=1 600w, https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=340&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=340&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=427&fit=crop&dpr=1 754w, https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=427&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/575444/original/file-20240213-30-vbeqfp.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=427&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Mutations that confer resistance against phages (red) early on will spawn a large number of phage-resistant variants, while mutations that occur later on will spawn only a few resistant variants.</span>
<span class="attribution"><span class="source">Qi Zheng</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Like small-prize cash-outs in slot machines, late-generation mutations occur more often but give fewer resistant variants. Like jackpots, early-generation mutations occur rarely but give large numbers of variants. Early-generation mutations are rare because early on there are only a small number of bacteria available to mutate.</p>
<p>For example, in a 20-generation experiment, a mutation occurring at the 10th generation of bacteria would give 1,024 phage-resistant variants. A mutation occurring at the 17th generation would give only four phage-resistant variants. </p>
<p>The number of resistant colonies in Luria’s experiments showed a similar pattern to that of slot machine cash-outs. Most dishes contained no or small numbers of mutant colonies, but several contained a large number of mutant colonies that Luria considered jackpots. This meant that the bacteria developed resistant variants before they interacted with the phages in the dishes.</p>
<h2>An experiment’s legacy</h2>
<p>Luria sent a note to Delbrück after his experiment was completed, asking him to check his work. The two scientists then worked together to write <a href="https://doi.org/10.1093/genetics/28.6.491">a classic paper</a> describing the experimental protocol and a theoretical framework to measure bacterial mutation rates.</p>
<p>Other scientists conducted similar experiments by replacing phages <a href="https://doi.org/10.1073/pnas.31.1.16">with penicillin</a> and with <a href="https://doi.org/10.1128/am.20.5.810-814.1970">tuberculosis drugs</a>. Similarly, they found that bacteria did not need to encounter an antibiotic to acquire resistance to it.</p>
<p>Bacteria have relied on random mutations to cope with harsh, constantly changing environments <a href="https://theconversation.com/antibiotic-resistance-is-not-new-it-existed-long-before-people-used-drugs-to-kill-bacteria-115836">for millions of years</a>. Their incessant, random mutations will lead them to inevitably develop variants that are resistant to the antibiotics of the future. </p>
<p>Drug resistance is a reality of life we will have to accept and continue to fight against.</p><img src="https://counter.theconversation.com/content/220283/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Qi Zheng does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The Nobel Prize-winning Luria−Delbrück experiment showed that random mutations in bacteria can allow them to develop resistance by chance.Qi Zheng, Professor of Biostatistics, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2230082024-02-21T03:45:57Z2024-02-21T03:45:57ZWhy do I keep getting urinary tract infections? And why are chronic UTIs so hard to treat?<figure><img src="https://images.theconversation.com/files/576612/original/file-20240219-26-qkb5eg.jpg?ixlib=rb-1.1.0&rect=209%2C473%2C7139%2C4429&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-tired-young-tattooed-business-woman-1703410366">BAZA Productions/Shutterstock</a></span></figcaption></figure><p>Dealing with chronic urinary tract infections (UTIs) means facing more than the occasional discomfort. It’s like being on a never ending battlefield against an unseen adversary, making simple daily activities a trial.</p>
<p>UTIs happen when bacteria sneak into the urinary system, causing pain and frequent trips to the bathroom. </p>
<p>Chronic UTIs take this to the next level, coming back repeatedly or never fully going away despite treatment. <a href="https://www.ncbi.nlm.nih.gov/books/NBK557479/">Chronic UTIs</a> are typically diagnosed when a person experiences two or more infections within six months or three or more within a year.</p>
<p>They can happen to anyone, but some are more prone due to their <a href="https://www.urologyhealth.org/urology-a-z/u/urinary-tract-infections-in-adults">body’s makeup or habits</a>. Women are more likely to get UTIs than men, due to their shorter urethra and hormonal changes during menopause that can decrease the protective lining of the urinary tract. Sexually active people are also at greater risk, as bacteria can be transferred around the area.</p>
<p>Up to <a href="https://www.urologyhealth.org/urology-a-z/u/urinary-tract-infections-in-adults#Related%20Resources">60% of women</a> will have at least one UTI in their lifetime. While effective treatments exist, <a href="https://www.health.harvard.edu/bladder-and-bowel/when-urinary-tract-infections-keep-coming-back#:%7E:text=Your%20urine%20might%20be%20cloudy,they%20take%20on%20your%20life.">about 25%</a> of women face recurrent infections within six months. Around <a href="https://sciendo.com/article/10.33073/pjm-2019-048?tab=article">20–30%</a> of UTIs don’t respond to standard antibiotic. The challenge of chronic UTIs lies in bacteria’s ability to shield themselves against treatments.</p>
<h2>Why are chronic UTIs so hard to treat?</h2>
<p>Once thought of as straightforward infections cured by antibiotics, we now know chronic UTIs are complex. The cunning nature of the bacteria responsible for the condition allows them to hide in bladder walls, out of antibiotics’ reach. </p>
<p>The bacteria form biofilms, a kind of protective barrier that makes them nearly impervious to standard antibiotic treatments. </p>
<p>This ability to evade treatment has led to a troubling <a href="https://theconversation.com/rising-antibiotic-resistance-in-utis-could-cost-australia-1-6-billion-a-year-by-2030-heres-how-to-curb-it-149543">increase in antibiotic resistance</a>, a global health concern that renders some of the conventional treatments ineffective.</p>
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<p>
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<strong>
Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
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<figure class="align-center ">
<img alt="Underpants hanging on a clothesline" src="https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/576616/original/file-20240219-28-iawpj7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Some antibiotics no longer work against UTIs.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/womens-underwear-hangs-on-clothesline-687500683">Michael Ebardt/Shutterstock</a></span>
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<p>Antibiotics need to be advanced to keep up with evolving bacteria, in a similar way to the flu vaccine, which is updated annually to combat the latest strains of the flu virus. If we used the same flu vaccine year after year, its effectiveness would wane, just as overused antibiotics lose their power against bacteria that have adapted. </p>
<p>But fighting bacteria that resist antibiotics is much tougher than updating the flu vaccine. Bacteria change in ways that are harder to predict, making it more challenging to create new, effective antibiotics. It’s like a never-ending game where the bacteria are always one step ahead.</p>
<p>Treating chronic UTIs still relies heavily on antibiotics, but doctors are getting crafty, changing up medications or prescribing low doses over a longer time to outwit the bacteria. </p>
<p>Doctors are also placing a greater emphasis on thorough diagnostics to accurately identify chronic UTIs from the outset. By asking detailed questions about the duration and frequency of symptoms, health-care providers can better distinguish between isolated UTI episodes and chronic conditions. </p>
<p>The approach to initial treatment can significantly influence the likelihood of a UTI becoming chronic. Early, targeted therapy, based on the specific bacteria causing the infection and its antibiotic sensitivity, may reduce the risk of recurrence. </p>
<p>For post-menopausal women, <a href="https://link.springer.com/article/10.1007/s00192-020-04397-z">estrogen therapy</a> has shown promise in reducing the risk of recurrent UTIs. After menopause, the decrease in estrogen levels can lead to changes in the urinary tract that makes it more susceptible to infections. This treatment restores the balance of the vaginal and urinary tract environments, making it less likely for UTIs to occur.</p>
<p>Lifestyle changes, such as <a href="https://journals.lww.com/co-nephrolhypertens/FullText/2013/05001/Impact_of_fluid_intake_in_the_prevention_of.1.aspx">drinking more water</a> and practising good hygiene like washing hands with soap after going to the toilet and the recommended front-to-back wiping for women, also play a big role. </p>
<p>Some swear by cranberry juice or supplements, though researchers are still figuring out <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001322.pub2/full">how effective these remedies truly are</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/cranberry-juice-can-prevent-recurrent-utis-but-only-for-some-people-203926">Cranberry juice can prevent recurrent UTIs, but only for some people</a>
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</em>
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<h2>What treatments might we see in the future?</h2>
<p>Scientists are currently working on new treatments for chronic UTIs. One promising avenue is the development of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052183/pdf/pathogens-12-00359.pdf">vaccines</a> aimed at preventing UTIs altogether, much like flu shots prepare our immune system to fend off the flu. </p>
<figure class="align-center ">
<img alt="Gynaecologist talks to patient" src="https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/576617/original/file-20240219-16-qgkamv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Emerging treatments could help clear chronic UTIs.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/gynecologist-talks-patient-during-medical-consultation-2298674535">guys_who_shoot/Shutterstock</a></span>
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<p>Another new method being looked at is called <a href="https://link.springer.com/article/10.1007/s12223-019-00750-y">phage therapy</a>. It uses special viruses called bacteriophages that go after and kill only the bad bacteria causing UTIs, while leaving the good bacteria in our body alone. This way, it doesn’t make the bacteria resistant to treatment, which is a big plus. </p>
<p>Researchers are also exploring the potential of <a href="https://www.mdpi.com/2079-6382/12/1/167">probiotics</a>. Probiotics introduce beneficial bacteria into the urinary tract to out-compete harmful pathogens. These good bacteria work by occupying space and resources in the urinary tract, making it harder for harmful pathogens to establish themselves. </p>
<p>Probiotics can also produce substances that inhibit the growth of harmful bacteria and enhance the body’s immune response.</p>
<p>Chronic UTIs represent a stubborn challenge, but with a mix of current treatments and promising research, we’re getting closer to a day when chronic UTIs are a thing of the past.</p>
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Read more:
<a href="https://theconversation.com/phage-therapy-could-treat-some-drug-resistant-superbug-infections-but-comes-with-unique-challenges-207025">'Phage therapy' could treat some drug-resistant superbug infections, but comes with unique challenges</a>
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<img src="https://counter.theconversation.com/content/223008/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Iris Lim does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Chronic UTIs come back repeatedly or never fully go away despite treatment.Iris Lim, Assistant Professor, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2215112024-01-29T14:53:48Z2024-01-29T14:53:48ZFrom mud and vinegar to 3D printing skin, the way we treat wounds still challenges humanity<p>Whether it’s the sting of a paper cut or the trauma of battle injury, wounds are woven into the tapestry of human experience. And since ancient times, we’ve fought the enemy that lurks within them – infection. </p>
<p>The constant threat of injury on the battlefield led to the search for new ways to combat wound infection. But early surgical procedures lacked the sterile instruments available today, meaning that for many years, surgery came with the added risk of post-operative <a href="https://cha.com/wp-content/uploads/2017/11/AJIC-2012-Infection-Control-Through-the-Ages.pdf">wound infection</a>, resulting in high numbers of deaths. </p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601883/">Ancient practices</a>, such as using oils, mud, turpentine, or honey to treat wounds, were common around 2000BC. The Greek physician Hippocrates (460-377BC) <a href="https://www.dermatologytimes.com/view/acetic-acid-and-wound-healing">used vinegar</a> to clean wounds, followed by bandaging to keep dirt at bay.</p>
<p>While the first hospitals were <a href="https://scientificsurgery.bjs.co.uk/article/the-surgery-of-theodoric-ca-a-d-1267-translated-from-the-latin-by-eldridge-campbell-m-d-and-james-colton-m-a-volume-i-books-i-and-ii-8-38-x-5-12-in-pp-223-xi-with-coloured-front/">established</a> in Europe in the middle ages, they were dangerous and brutal places. Wound infection rates were high because of unsanitary conditions and the use of cautery, which involved pushing a burning iron into a patient’s wound until it reached the bone.</p>
<figure class="align-center ">
<img alt="A drawing of a pot containing a fire with several medical instruments poking out of it." src="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=403&fit=crop&dpr=1 600w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=403&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=403&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/571587/original/file-20240126-19-5nmbkg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">A receptacle for burning coal to heat cautery instruments.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/gcg933n2/images?id=jghkdnp4">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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</figure>
<p>By the 1860s, the pioneering surgeon Joseph Lister had revolutionised wound infection treatment by introducing <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2895849/">carbolic-acid-soaked bandages</a>. And Robert Wood Johnson, who founded Johnson & Johnson, <a href="https://wounds-uk.com/journal-articles/sterilised-gauze-and-baby-powder-robert-wood-johnson-i-and-frederick-barnett-kilmer/">produced</a> the first sterile gauze bandages by 1890. The combination of antiseptic and sterile bandage marked a turning point in the evolution of wound treatment and infection control.</p>
<p>The discovery of penicillin by <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520913/">Alexander Fleming</a> in 1928 was also a pivotal moment in the treatment of wound infections. By the 1940s, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369031/">penicillin</a> was being used to treat second world war soldiers who had wound infections that would have been deemed fatal in previous years. For less serious wounds, Lister’s approach of using a dressing and an antiseptic was still used.</p>
<p>Substances like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756674/">silver</a> and <a href="https://pubmed.ncbi.nlm.nih.gov/12914356/">iodine</a> have also been recognised for their antimicrobial properties since the 1800s. Iodine, though effective, caused pain and skin discolouration until safer and less painful formulations were developed in 1949. <a href="https://bnf.nice.org.uk/wound-management/antimicrobial-dressings/">These formulations</a> endure in modern wound dressings.</p>
<p>For everyday cuts and scrapes, a simple cleaning with water and application of antiseptic cream is usually enough. This helps to prevent the inadvertent introduction of bacteria into the wound, minimising the risk of additional pain and swelling. </p>
<p>But while most wounds nowadays heal without issue, some become become infected. Research published in 2021 showed that <a href="https://wounds-uk.com/wp-content/uploads/sites/2/2023/02/68803cd147c4d81a02b9cc56823f19a1.pdf">3.8 million</a> people were having their wounds managed by the NHS between 2017 and 2018, up 71% from between 2012 and 2013. They included surgical wounds, leg ulcers and burns. This shows how hard it can be to care for wounds that are difficult to heal and particularly susceptible to infections.</p>
<h2>Modern-day challenges</h2>
<p>One of the biggest challenges in the modern-day treatment of wound infection is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">antibiotic resistance</a>. This happens when bacteria develop the ability to defeat the drugs designed to kill them. Resistant infections can be difficult, and sometimes impossible, to treat. </p>
<p>Many bacteria have also become resistant to the antimicrobial ingredients used in wound dressings. This is the case for <a href="https://www.sciencedirect.com/science/article/pii/S0195670104005201">silver-based</a> wound dressings, which are often used to treat chronic wound infections. This type of wound characteristically <a href="https://www.nature.com/articles/s41572-022-00377-3">fails to heal</a>, and can remain an open, infected wound for many months – or even years. As well as the devastating effect on people’s quality of life, this also places a huge financial burden on the NHS.</p>
<p>The constant fight against wound infections drives extensive research for new, safe and effective treatments. While progress is being made, a crucial hurdle lies in the <a href="https://academic.oup.com/jacamr/article/3/1/dlab027/6186407">limitations</a> of laboratory testing methods. These tests, while necessary for regulatory approval, often fail to capture the nuanced realities of wounds in the human body. </p>
<p>No two people are the same and no two wounds are the same either. This can lead to situations where treatments shine in the lab but ultimately prove ineffective in real patients.</p>
<h2>Creating wound models</h2>
<p>In response to this, scientists are tackling the limitations of lab tests by creating more realistic synthetic wound models. Some are even <a href="https://pubmed.ncbi.nlm.nih.gov/30172300/">3D printing</a> human skin (using leftovers from surgical procedures), or animal skin, complete with artificial body fluids, such as pus. The aim is to create a model environment that mimics real wounds more accurately. </p>
<p>Recently, my own <a href="https://pubmed.ncbi.nlm.nih.gov/36678466/">research group</a> has made strides in developing lab models that act like real chronic wounds when treated with antimicrobial dressings. While not perfect, our models are a step in the right direction, contributing to the development of formulations with promising potential for treating wound infections in the future.</p>
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Read more:
<a href="https://theconversation.com/we-built-a-human-skin-printer-from-lego-and-we-want-every-lab-to-use-our-blueprint-203170">We built a human-skin printer from Lego and we want every lab to use our blueprint</a>
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<p>As we navigate the complexities of wound care, the quest for new, effective and safe treatments continues, driven by the efforts of scientists worldwide. We are working towards a future where the management of difficult-to-heal wounds and infections improves, enhancing both individual wellbeing and the efficiency of health systems.</p><img src="https://counter.theconversation.com/content/221511/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Sarah Maddocks does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Keeping wounds clean and infection free has challenged people for thousands of years.Sarah Maddocks, Lecturer in Microbiology, Cardiff Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2205642024-01-05T14:54:09Z2024-01-05T14:54:09ZNew antibiotic zosurabalpin shows promise against drug-resistant bacteria – an expert explains how it works<figure><img src="https://images.theconversation.com/files/567989/original/file-20240105-24-a6i28q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5120%2C2880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Carbapenem-resistant Acinetobacter baumannii is classified as a priority 1 critical pathogen by the World Health Organization</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-science-laboratory-portrait-beautiful-black-1922200124">Gorodenkoff/Shutterstock</a></span></figcaption></figure><p>Researchers have <a href="https://www.nature.com/articles/s41586-023-06799-7">identified</a> an entirely new class of antibiotic that can kill bacteria that are resistant to most current drugs. </p>
<p>Zosurabalpin is highly effective against the bacterium carbapenem-resistant <em>Acinetobacter baumannii</em> (Crab), which is <a href="https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed">classified</a> as a “priority 1” pathogen by the World Health Organization due to its growing presence in hospitals.</p>
<p>Crab <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137960/">can kill</a> up to 60% of people infected with it. It commonly causes infections of the urinary tract, respiratory tract and blood stream, potentially leading to sepsis. It is responsible for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913636/">around 20%</a> of infections in places like hospitals, care homes or other similar healthcare settings.</p>
<p>Antibiotics commonly work by crossing the cell wall that surrounds infectious bacteria to reach the vital machinery inside. Once inside the cell, antibiotics block that machinery in such a way as to either stop the bacteria from growing or to cause cell death. </p>
<p>Crab is a clinical challenge as it has a double-layered cell wall, a feature that microbiologists describe as “<a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/gram-negative-bacteria">gram negative</a>”. This means that antibiotics need to cross both layers to reach the vital machinery inside the bacteria to kill them and treat the infection. </p>
<p>An exception to this rule is penicillin-based antibiotics, where the target is in the cell wall itself. These antibiotics, known as <a href="https://www.bmj.com/content/344/bmj.e3236">carbapenems</a>, were derived from penicillin some 48 years after it was first discovered and still work in the same way. However, they have undergone clever chemical modification to prevent bacteria successfully evolving to resist them. This makes them a vital part of treating infections like those caused by <em>Acinetobacter baumannii</em>. </p>
<p>But Crab, the superbug version of this infection, has developed the ability to break down carbapenems, giving it an evolutionary upper hand, which has led to its rise to supremacy in hospitals. </p>
<h2>Zosurabalpin</h2>
<p>This new class of antibiotic, zosurabalpin, is shown to be highly effective against Crab both in the laboratory and in infected animals. Researchers tested zosurabalpin against more than 100 Crab samples from patients suffering from the infection. The research team, <a href="https://www.nature.com/articles/s41586-023-06799-7">found</a> that zosurabalpin was able to kill all of these bacterial strains. It could also kill the bacteria in the bloodstream of mice infected with Crab, preventing them from developing sepsis. </p>
<p>Crab has the ability to make a toxin called <a href="https://www.sciencedirect.com/topics/neuroscience/lipopolysaccharide">lipopolysaccharide</a> that it uses as part of its weaponry for infecting people and which it normally embeds into its outer cell wall. </p>
<p>Zosurabalpin works by blocking a molecular machine called <a href="https://www.nature.com/articles/s41586-023-06873-0">LptB2FGC</a> that transports the lipopolysaccharide toxin from the inside barrier to the outside one. This makes the toxin build up inside the bacteria, causing the Crab cells to die. Essentially, the bacteria pull the pin out of their own grenade but zosurabalpin stops them from being able to throw it. </p>
<p>This LptB2FGC mechanism is pretty unique to Crab, which has some advantages and disadvantages. The bad news is that zosurabalpin will only kill Crab infections and not those caused by other types of bacteria. This means doctors would need to accurately diagnose patients with this infection to decide if zosurabalpin would be the right drug. </p>
<p>But a major advantage is that the chance of antibiotic resistance emerging is reduced, as this resistance could only emerge from Crab and not other types of bacteria. Hopefully, this could extend the shelf life of this drug. </p>
<p>The researchers say they have already seen some mutations in the drug target, LptB2FGC. However, these only seem to reduce the effectiveness of zosurabalpin, rather than stopping it working entirely. The great news is that this is the first time an antibiotic has been reported to work in this way. It gives microbiologists a new avenue to explore ways to kill our bacterial enemies before they kill us. </p>
<figure class="align-center ">
<img alt="Close up of microscope with lab glassware." src="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Zosurabalpin is effective against the bacteria, Crab, which can kill up to 60% of people infected with it.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/microscope-lab-glassware-science-laboratory-research-530971462">totojang1977/Shutterstock</a></span>
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<p>Zosurabalpin is now in phase 1 clinical trial for use in patients infected with Crab. This early testing in humans will help the company developing the drug, Roche, to work out any side effects of the drugs as well as potential toxicity. Most importantly, they need to check that the drug works just as well in humans as it did in mice, and look to see if any antibiotic resistance emerges in the trial patients. </p>
<p>It’s early days and the failure rate for new antibiotic development is high, but scientists are rising to the challenge. This discovery offers significant opportunities to the scientific field as a whole and a vital lifeline in the fight against antibiotic-resistant infections.</p><img src="https://counter.theconversation.com/content/220564/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Cox receives research funding from UKRI, charities and industry.
He is Co-Director of the Antibiotic Discovery Accelerator (ABX) Network </span></em></p>Zosurabalpin is highly effective against dangerous bacterium Crab, which can kill up to 60% of people infected with it.Jonathan Cox, Senior Lecturer in Microbiology, Aston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2188792023-12-11T22:10:48Z2023-12-11T22:10:48ZAntimicrobial resistance now hits lower-income countries the hardest, but superbugs are a global threat we must all fight<figure><img src="https://images.theconversation.com/files/564957/original/file-20231211-23-x9nrkx.jpg?ixlib=rb-1.1.0&rect=907%2C341%2C5083%2C3646&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">While antimicrobial resistance is a threat to all humanity, a tale of two worlds emerges, highlighting the heightened vulnerability of low- and middle-income countries.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/antimicrobial-resistance-now-hits-lower-income-countries-the-hardest-but-superbugs-are-a-global-threat-we-must-all-fight" width="100%" height="400"></iframe>
<p>Antimicrobial resistance (AMR) is one of the World Health Organization’s <a href="https://www.who.int/news-room/photo-story/photo-story-detail/urgent-health-challenges-for-the-next-decade?utm_source=STAT+Newsletters&utm_campaign=1931cb646b-MR_COPY_02&utm_medium=email&utm_term=0_8cab1d7961-1931cb646b-150708293">most urgent health challenges</a> for the next decade. While AMR is a global threat, a tale of two worlds emerges, highlighting the heightened vulnerability of low- and middle-income countries (<a href="https://data.worldbank.org/country/XO">LMICs</a>). </p>
<p>Misuse of antimicrobials worldwide has accelerated the evolution of <a href="https://www.who.int/health-topics/antimicrobial-resistance">antimicrobial resistance</a>. For instance, in many countries, antibiotics are available over the counter, and even when their use is more regulated, the Centers for Disease Control has estimated that in the United States, <a href="https://www.cdc.gov/antibiotic-use/data/outpatient-prescribing/index.html">one in three antibiotic prescriptions</a> were unnecessary. </p>
<p>Likewise, most of the antibiotics are not even given to humans. As much as 80 per cent of the total consumption is <a href="https://doi.org/10.1056/NEJMp1311479">used in livestock</a> to promote growth, and to treat or prevent infections. </p>
<p>This has facilitated bacteria and other microorganisms to become resistant to the drugs that were once effective in treating them — sometimes called <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">superbugs</a>. This problem was associated with <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">4.95 million deaths</a> worldwide in 2019.</p>
<h2>A ‘silent pandemic’</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="clusters of round ivory shapes against a blue background" src="https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=453&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=453&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=453&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=570&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=570&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564438/original/file-20231208-17-v6wlih.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=570&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Microscopic view of methicillin-resistant Staphylococcus aureus (MRSA) bacteria.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
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<p>If we don’t take action, things could get even worse. Reports predict that by 2050, AMR could cause <a href="https://amr-review.org/">10 million deaths</a> each year and cost the world <a href="https://www.who.int/news/item/22-06-2023-who-outlines-40-research-priorities-on-antimicrobial-resistance">US$100 trillion</a>. </p>
<p>Fortunately, many nations are now taking decisive steps toward controlling what the WHO calls a “<a href="https://www.who.int/news-room/articles-detail/global-antimicrobial-resistance-forum-launched-to-help-tackle-common-threat-to-planetary-health">silent pandemic</a>.” Acknowledging the gravity of the situation, high-income countries (<a href="https://data.worldbank.org/income-level/high-income">HICs</a>) such as the U.S. and Canada have <a href="https://doi.org/10.1016/S2214-109X(23)00019-0">implemented robust plans</a> encompassing surveillance, stewardship and policy reforms. </p>
<p>These efforts should undoubtedly be applauded. However, an important principle of the “<a href="https://www.who.int/news-room/questions-and-answers/item/one-health">One Health</a>” approach, which is often neglected, is that this is a global problem, and global collaboration should be prioritized. Low- and middle-income countries bear a <a href="https://doi.org/10.1080/14787210.2021.1951705">disproportionate burden</a> of AMR and require increased resource mobilization, knowledge sharing and international co-operation.</p>
<h2>Contrasting realities</h2>
<p>As a doctoral researcher, I study the evolution of antimicrobial resistance in bacteria, but as an immigrant from Mexico, I am deeply concerned with the disparity observed between high-income and low- and middle-income countries, and their contrasting realities. </p>
<figure class="align-center ">
<img alt="A row of three petri dishes with varying levels of growth" src="https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=240&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=240&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=240&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=302&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=302&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564955/original/file-20231211-17-l64ftv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=302&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antimicrobial resistance susceptibility lab tests.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>For instance, there have been great efforts in <a href="https://doi.org/10.1016/S1473-3099(11)70054-8">regulating antibiotic consumption</a> in many HICs, where antibiotic use in livestock has decreased and antibiotics are only accessible under prescription. While there is still room for improvement, there is a less encouraging reality in some LMICs, where antibiotics are usually obtained easily <a href="https://doi.org/10.1016/S1473-3099(11)70054-8">without prescriptions</a> and sometimes used as a way to compensate for the <a href="https://doi.org/10.1080/14787210.2021.1951705">difficulty of accessing health-care professionals</a>. </p>
<p>Likewise, in some LMICs, antibiotic use in animals is predicted to <a href="https://doi.org/10.1073/pnas.1503141112">double by 2030</a> compared to the last decade.</p>
<p>A <a href="https://doi.org/10.1016/j.lana.2023.100594">recent report</a> exploring the burden of AMR in the Americas in 2019 showed the “multiple realities” of the problem. Not surprisingly, by 2019, the four countries with the lowest AMR-linked mortality rates (age-standardized) each had a financed national action plan to combat AMR, while none of the 10 countries with the highest mortality rates did. </p>
<p>Strikingly, <a href="https://www.unicef.org/wash">UNICEF reports</a> that more than half of the world’s population does not have access to safe sanitation and over 2.2 billion people still don’t have access to safe drinking water. This is extremely concerning for a variety of reasons, but good sanitation and hygiene is critical to <a href="https://www.who.int/teams/environment-climate-change-and-health/water-sanitation-and-health/burden-of-disease/wash-and-antimicrobial-resistance#:%7E:text=Improvements%20in%20water%20sanitation%20and,Action%20Plan%20to%20combat%20AMR.">limiting the spread of microbes and reducing the risk of infection</a>.</p>
<p>The current approach taken by most high-income countries is the equivalent of sheltering in the attic, making sure the fire alarm works correctly, while the basement is on fire.</p>
<h2>Worldwide spread</h2>
<figure class="align-right ">
<img alt="Infographic of resistant bacteria spreading around the globe" src="https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/564440/original/file-20231208-19-jfdagi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Resistant bacteria or resistance genes can spread across countries through travel, immigration, trade and even water and air circulation.</span>
<span class="attribution"><span class="source">(Centers for Disease Control and Prevention)</span></span>
</figcaption>
</figure>
<p>Resistant bacteria can evolve anywhere. Even if some countries manage to control the problem within their borders, the risk remains. Resistant bacteria or genes that allow bacteria to grow in the presence of the antibiotic can spread across countries through various means, including travel, immigration, trade and even natural processes like water and air circulation. </p>
<p>Such is the case of the resistance gene <a href="https://doi.org/10.1128/aac.00774-09">NDM-1</a>, which was first described in 2009. Only five years after the initial report, this resistance gene was present in virtually the <a href="https://doi.org/10.1111/1469-0691.12719">whole world</a>.</p>
<p>We have all observed the phenomenon of worldwide spread firsthand, as the COVID-19 pandemic vividly demonstrates how pathogens can <a href="https://coronavirus.jhu.edu/map.html">rapidly traverse the globe</a>. </p>
<h2>Communication and collaboration</h2>
<p>It is crucial for nations to enhance communication channels and promote education regarding AMR in several sectors, including the general public, health-care providers, farmers and veterinarians. In addition to this, there is a pressing need to establish robust surveillance systems that can promptly detect outbreaks and enable swift action. </p>
<p>Effective cross-border communication could be realized through standardizing surveillance systems. This would enable accurate comparisons of results between countries. Moreover, it facilitates the sharing of valuable resources, equipment, qualified personnel and access to training opportunities. </p>
<p>Both HICs and LMICs should collaborate closely to implement measures aimed at reducing infection rates, such as improved sanitation practices. This collaboration encourages the exchange of knowledge and expertise, enabling the adoption of best practices globally.</p>
<p>The United Kingdom government set a good example in August, when it allocated <a href="https://www.gov.uk/government/news/210-million-to-tackle-deadly-antimicrobial-resistance">£210 million</a> (about C$360 million) to tackle AMR across Asia and Africa over the next three years, understanding that this threat cannot be fought from its own trenches. These resources will increase surveillance in 25 countries where the AMR threat is highest, and will also be used to upgrade laboratories and strengthen the health workforce in those countries. </p>
<p>To effectively combat AMR, global co-operation is not a luxury but a necessity. HICs must recognize their responsibility to support LMICs in addressing this crisis. By sharing resources, knowledge and expertise, we can collectively mitigate the threat of AMR. </p>
<p>By safeguarding the effectiveness of antibiotics, we protect ourselves and future generations from the devastating consequences of antimicrobial resistance. Together, we can make a difference in the global fight against superbugs.</p><img src="https://counter.theconversation.com/content/218879/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Laura Domínguez has received funding from FRQNT, Concordia University and Mitacs. </span></em></p>The contrasting realities of antimicrobial resistance between high-income countries and low- and middle-income countries demands international co-operation to effectively fight superbugs.Laura Domínguez, Doctoral Researcher and Public Scholar, Biochemistry, Concordia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2179202023-11-29T03:33:38Z2023-11-29T03:33:38ZDo you really need antibiotics? Curbing our use helps fight drug-resistant bacteria<p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>Antibiotic resistance occurs when a microorganism changes and no longer responds to an antibiotic that was previously effective. It’s <a href="https://thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00502-2/fulltext">associated with</a> poorer outcomes, a greater chance of death and higher health-care costs. </p>
<p>In Australia, antibiotic resistance means some patients are admitted to hospital because oral antibiotics are <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">no longer effective</a> and they need to receive intravenous therapy via a drip. </p>
<p>Antibiotic resistance is rising to high levels in certain parts of the world. Some hospitals <a href="https://www.reactgroup.org/news-and-views/news-and-opinions/year-2022/the-impact-of-antibiotic-resistance-on-cancer-treatment-especially-in-low-and-middle-income-countries-and-the-way-forward/">have to consider</a> whether it’s even viable to treat cancers or perform surgery due to the risk of antibiotic-resistant infections.</p>
<p>Australia is <a href="https://www.safetyandquality.gov.au/our-work/antimicrobial-resistance/antimicrobial-use-and-resistance-australia-aura/aura-2023-fifth-australian-report-antimicrobial-use-and-resistance-human-health">one of the highest users</a> of antibiotics in the developed world. We need to use this precious resource wisely, or we risk a future where a simple infection could kill you because there isn’t an effective antibiotic. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-rise-and-fall-of-antibiotics-what-would-a-post-antibiotic-world-look-like-213450">The rise and fall of antibiotics. What would a post-antibiotic world look like?</a>
</strong>
</em>
</p>
<hr>
<h2>When should antibiotics not be used?</h2>
<p>Antibiotics only work for some infections. They work against bacteria but <a href="https://www.safetyandquality.gov.au/publications-and-resources/resource-library/do-i-really-need-antibiotics">don’t treat</a> infections caused by viruses. </p>
<p>Most community acquired infections, even those caused by bacteria, are likely to get better without antibiotics. </p>
<p>Taking an antibiotic when you don’t need it won’t make you feel better or recover sooner. But it can increase your chance of side effects like nausea and diarrhoea.</p>
<p>Some people think green mucus (or snot) is a sign of bacterial infection, requiring antibiotics. But it’s actually <a href="https://www.safetyandquality.gov.au/sites/default/files/2023-11/aura_2023_do_i_really_need_antibiotics.pdf">a sign</a> your immune system is working to fight your infection.</p>
<h2>If you wait, you’ll often get better</h2>
<p><a href="https://www.tg.org.au/">Clinical practice guidelines</a> for antibiotic use aim to ensure patients receive antibiotics when appropriate. Yet 40% of GPs say they prescribe antibiotics <a href="https://doi.org/10.1071/HI13019">to meet patient expectations</a>. And <a href="https://pubmed.ncbi.nlm.nih.gov/35973750/">one in five</a> patients expect antibiotics for respiratory infections. </p>
<figure class="align-center ">
<img alt="Man blows nose and looks at thermometre" src="https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/562071/original/file-20231128-19-5kijmo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Doctors sometimes tell patients to ‘watch and wait’.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-man-blowing-his-nose-checking-2276021157">Shutterstock</a></span>
</figcaption>
</figure>
<p>It can be difficult for doctors to decide if a patient has a viral respiratory infection or are at an early stage of serious bacterial infection, particularly in children. One option is to “watch and wait” and ask patients to return if there is clinical deterioration. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/no-antibiotics-arent-always-needed-heres-how-gps-can-avoid-overprescribing-213981">No, antibiotics aren't always needed. Here's how GPs can avoid overprescribing</a>
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</em>
</p>
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<p>An alternative is to prescribe an antibiotic but advise the patient to not have it dispensed unless specific symptoms occur. This can <a href="https://doi.org/10.1002/14651858.CD004417.pub5">reduce antibiotic use by 50%</a> with no decrease in patient satisfaction, and no increase in complication rates. </p>
<h2>Sometimes antibiotics are life-savers</h2>
<p>For some people – particularly those with a weakened immune system – a simple infection can become more serious. </p>
<p>Patients with life-threatening suspected infections should receive an appropriate antibiotic <a href="https://www.safetyandquality.gov.au/our-work/clinical-care-standards/antimicrobial-stewardship-clinical-care-standard">immediately</a>. This includes serious infections such as <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/bacterial-meningitis#:%7E:text=What%20is%20bacterial%20meningitis%3F,can%20cause%20life%2Dthreatening%20problems.">bacterial meningitis</a> (infection of the membranes surrounding the brain)
and <a href="https://clinicalexcellence.qld.gov.au/priority-areas/safety-and-quality/sepsis/adult-sepsis#:%7E:text=Adult%20patients%20with%20sepsis%20also,adult%20emergency%20department%20sepsis%20pathway.">sepsis</a> (which can lead to organ failure and even death).</p>
<h2>When else might antibiotics be used?</h2>
<p>Antibiotics are sometimes used to prevent infections in patients who are undergoing surgery and are at significant risk of infection, such as those undergoing bowel resection. These patients will <a href="https://www.tg.org.au">generally receive</a> a single dose before the procedure.</p>
<p>Antibiotics may also <a href="https://www.tg.org.au">be given</a> to patients undergoing chemotherapy for solid organ cancers (of the breast or prostate, for example), if they are at high risk of infection. </p>
<p>While most sore throats are caused by a virus and usually resolve on their own, some high risk patients with a bacterial strep A infection which can cause “scarlet fever” are given antibiotics to prevent a more serious infection like <a href="https://www.rhdaustralia.org.au/">acute rheumatic fever</a>. </p>
<h2>How long is a course of antibiotics?</h2>
<p>The recommended duration of a course of antibiotics depends on the type of infection, the likely cause, where it is in your body and how effective the antibiotics are at killing the bacteria. </p>
<p>In the past, courses were largely arbitrary and based on assumptions that antibiotics should be taken for long enough to eliminate the infecting bacteria. </p>
<figure class="align-center ">
<img alt="Pharmacist handing over antibiotics to a patient" src="https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/562075/original/file-20231128-23-l3ap7p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">The duration of antibiotic courses has shortened.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmasict-serving-customer-drug-store-1855116610">Shutterstock</a></span>
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</figure>
<p>More recent research does not support this and shorter courses are <a href="https://www.acpjournals.org/doi/full/10.7326/M19-1509">nearly always as effective as longer ones</a>, particularly for community acquired respiratory infections. </p>
<p>For <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736742/">community acquired pneumonia</a>, for example, research shows a three- to five-day course of antibiotics is at least as effective as a seven- to 14-day course. </p>
<p>The “take until all finished” approach is no longer recommended, as the longer the antibiotic exposure, the greater the chance the bacteria will develop resistance. </p>
<p>However, for infections where it is more difficult to eradicate the bacteria, such as tuberculosis and bone infections, a combination of antibiotics for many months is usually required. </p>
<h2>What if your infection is drug-resistant?</h2>
<p>You may have an antibiotic-resistant infection if you don’t get better after treatment with standard antibiotics. </p>
<p>Your clinician will collect samples for lab testing if they suspect you have antibiotic-resistant infection, based on your travel history (especially if you’ve been hospitalised in a country with high rates of antibiotic resistance) and if you’ve had a recent course of antibiotics that hasn’t cleared your infection. </p>
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Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
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<p>Antibiotic-resistant infections are managed by prescribing broad-spectrum antibiotics. These are like a sledgehammer, wiping out many different species of bacteria. (Narrow-spectrum antibiotics conversely can be thought of as a scalpel, more targeted and only affecting one or two kinds of bacteria.) </p>
<p>Broad-spectrum antibiotics are usually more expensive and come with more severe side effects.</p>
<h2>What can patients do?</h2>
<p>Decisions about antibiotic prescriptions should be made using <a href="https://www.safetyandquality.gov.au/our-work/partnering-consumers/shared-decision-making/decision-support-tools-specific-conditions">shared decision aids</a>, where patients and prescribers discuss the risks and benefits of antibiotics for conditions like a sore throat, middle ear infection or acute bronchitis.</p>
<p>Consider asking your doctor questions such as:</p>
<ul>
<li>do we need to test the cause of my infection?</li>
<li>how long should my recovery take?</li>
<li>what are the risks and benefits of me taking antibiotics?</li>
<li>will the antibiotic affect my regular medicines?</li>
<li>how should I take the antibiotic (how often, for how long)?</li>
</ul>
<p>Other ways to fight antibiotic resistance include:</p>
<ul>
<li>returning leftover antibiotics to a pharmacy for safe disposal</li>
<li>never consuming leftover antibiotics or giving them to anyone else</li>
<li>not keeping prescription repeats for antibiotics “in case” you become sick again </li>
<li>asking your doctor or pharmacist what you can do to feel better and ease your symptoms rather than asking for antibiotics.</li>
</ul>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>. Listen to the podcast <a href="https://theconversation.com/antibiotic-resistance-microbiologists-turn-to-new-technologies-in-the-hunt-for-solutions-podcast-217615">here</a>.</em></p><img src="https://counter.theconversation.com/content/217920/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Minyon Avent has received funding from the Metro North Hospital and Health Service, the Children’s Hospital Foundation Queensland, the Department of Health, MSD and the Society of Hospital Pharmacists of Australia.</span></em></p><p class="fine-print"><em><span>Fiona Doukas has received funding from the Society of Hospital Pharmacists Australia and Hospira. She works for the Australian Commission on Safety and Quality in Health Care. She is part of an NGO called Hepatitis B Free. She works at two Sydney Hospitals. </span></em></p><p class="fine-print"><em><span>Kristin Xenos works for the Australian Commission on Safety and Quality in Health Care.</span></em></p>Australia is one of the highest users of antibiotics in the developed world. So when do we actually need antibiotics to treat an infection? And when should we avoid them?Minyon Avent, Antimicrobial Stewardship Pharmacist, The University of QueenslandFiona Doukas, PhD candidate, University of SydneyKristin Xenos, Research Assistant, College of Health, Medicine and Wellbeing, School of Biomedical Science and Pharmacy, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134602023-11-23T19:02:31Z2023-11-23T19:02:31ZDrug resistance may make common infections like thrush untreatable<p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
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<p>We’ve all heard about antibiotic resistance. This happens when bacteria develop strategies to avoid being destroyed by an antibiotic. </p>
<p>The consequences of antibiotic resistance mean an antibiotic previously used to cure bacterial infections no longer works effectively because the bacteria have become resistant to the drug. This means it’s getting harder to cure the infections some bacteria cause.</p>
<p>But unfortunately, it’s only one part of the problem. The same phenomenon is also happening with other causes of infections in humans: fungi, viruses and parasites.</p>
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<strong>
Read more:
<a href="https://theconversation.com/the-rise-and-fall-of-antibiotics-what-would-a-post-antibiotic-world-look-like-213450">The rise and fall of antibiotics. What would a post-antibiotic world look like?</a>
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<p>“Antimicrobial resistance” means the drugs used to treat diseases caused by microbes (bugs that cause infection) no longer work. This occurs with antibacterial agents used against bacteria, antifungal agents used against fungi, anti-parasitic agents used against parasites and antiviral agents used against viruses.</p>
<p>This means a wide range of previously controllable infections are becoming difficult to treat – and may become untreatable. </p>
<h2>Fighting fungi</h2>
<p>Fungi are responsible for a range of infections in humans. Tinea, ringworm and vulvovaginal candidiasis (thrush) are some of the more familiar and common superficial fungal infections. </p>
<p>There are also life-threatening fungal infections such as aspergillosis, cryptococcosis and invasive fungal bloodstream infections including those caused by <em>Candida albicans</em> and <em>Candida auris</em>. </p>
<p>Fungal resistance to antifungal agents is a problem for several reasons. </p>
<p>First, the range of antifungal agents available to treat fungal infections is limited, especially compared to the range of antibiotics available to treat bacterial infections. There are only four broad families of antifungal agents, with a small number of drugs in each category. Antifungal resistance further restricts already limited options.</p>
<p>Life-threatening fungal infections happen less frequently than life-threatening bacterial infections. But they’re rising in frequency, especially among people whose immune systems are compromised, including by <a href="https://7news.com.au/news/qld/first-heart-transplant-patient-to-die-from-fungal-infection-at-brisbanes-prince-charles-hospital-identified-as-mango-hill-gp-muhammad-hussain-c-12551559">organ transplants</a> and chemotherapy or immunotherapy for cancer. The threat of getting a drug-resistant fungal infection makes all of these health interventions riskier.</p>
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<strong>
Read more:
<a href="https://theconversation.com/how-do-candida-auris-and-other-fungi-develop-drug-resistance-a-microbiologist-explains-203495">How do _Candida auris_ and other fungi develop drug resistance? A microbiologist explains</a>
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</em>
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<p>The greatest <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2017.00735/full">burden of serious fungal disease</a> occurs in places with limited health-care resources available for diagnosing and treating the infections. Even if infections are diagnosed and antifungal treatment is available, antifungal resistance reduces the treatment options that will work.</p>
<p>But even in Australia, common fungal infections are impacted by resistance to antifungal agents. Vulvovaginal candidiasis, known as thrush and caused by <em>Candida</em> species and some closely related fungi, is usually reliably treated by a topical antifungal cream, sometimes supplemented with an oral tablet. However, instances of <a href="https://www.theage.com.au/national/victoria/they-can-t-sit-properly-doctors-treat-growing-number-of-women-with-chronic-thrush-20230913-p5e499.html">drug-resistant thrush</a> are increasing, and new treatments are needed.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1584939012753862657"}"></div></p>
<h2>Targeting viruses</h2>
<p>Even <a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">fewer antivirals</a> are available than antibacterial and antifungal agents. </p>
<p>Most antimicrobial treatments work by exploiting differences between the microbe causing the infection and the host (us) experiencing the infection. Since viruses use our cells to replicate and cause their infection, it’s difficult to find antiviral treatments that selectively target the virus without damaging us. </p>
<p>With so few antiviral drugs available, any resistance that develops to one of them significantly reduces the treatment options available. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">Why are there so many drugs to kill bacteria, but so few to tackle viruses?</a>
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<p>Take COVID, for example. Two antiviral medicines are in widespread use to treat this viral infection: Paxlovid (containing nirmatrelvir and ritonavir) and Lagevrio (molnupiravir). So far, SARS-CoV-2, the virus that causes COVID, has not developed significant resistance to either of these <a href="https://www.cidrap.umn.edu/covid-19/low-levels-resistance-paxlovid-seen-sars-cov-2-isolates">treatments</a>. </p>
<p>But if SARS-CoV-2 develops resistance to either one of them, it halves the treatment options. Subsequently relying on one would likely lead to its increased use, which may heighten the risk that resistance to the second agent will develop, leaving us with no antiviral agents to treat COVID. </p>
<p>The threat of antimicrobial resistance makes our ability to treat serious COVID infections rather precarious.</p>
<h2>Stopping parasites</h2>
<p>Another group of microbes that cause infections in humans are single-celled microbes such as <em>Plasmodium</em>, <em>Giardia</em>, <em>Leishmania</em>, and <em>Trypanosoma</em>. These microbes are sometimes referred to as parasites, and they are becoming increasingly resistant to the very limited range of anti-parasitic agents used to treat the infections they cause. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/antibiotic-resistance-microbiologists-turn-to-new-technologies-in-the-hunt-for-solutions-podcast-217615">Antibiotic resistance: microbiologists turn to new technologies in the hunt for solutions – podcast</a>
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<p>Several <em>Plasmodium</em> species cause malaria and anti-parasitic drugs have been the cornerstone of malaria treatment for decades. But their usefulness has been significantly reduced by the <a href="https://www.mmv.org/our-work/mmvs-pipeline-antimalarial-drugs/antimalarial-drug-resistance">development of resistance</a>. </p>
<p><em>Giardia</em> parasites cause an infection called giardiasis. This can resolve on its own, but it can also cause severe gastrointestinal symptoms such as diarrhea, nausea, and bloating. These microbes have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207226/">developed resistance</a> to the main treatments and patients infected with drug-resistant parasites can have protracted, unpleasant infections. </p>
<figure class="align-center ">
<img alt="3D illustration of Giardia lamblia protozoan" src="https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"><em>Giardia</em> parasites (illustrated here) cause giardiasis.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/giardia-lamblia-protozoan-causative-agent-giardiasis-1038065005">Shutterstock</a></span>
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<h2>Resistance is a natural consequence</h2>
<p>Treating infections influences microbes’ evolutionary processes. Exposure to drugs that stop or kill them pushes microbes to either evolve or die. The exposure to antimicrobial agents provokes the evolutionary process, selecting for microbes that are resistant and can survive the exposure. </p>
<p>The pressure to evolve, provoked by the antimicrobial treatment, is called “selection pressure”. While most microbes will die, a few will evolve in time to overcome the antimicrobial drugs used against them. </p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
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</em>
</p>
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<p>The evolutionary process that leads to the emergence of resistance is inevitable. But some things can be done to minimise this and the problems it brings. </p>
<p>Limiting the use of antimicrobial agents is one approach. This means reserving antimicrobial agents for when their use is known to be necessary, rather than using them “just in case”.</p>
<p>Antimicrobial agents are precious resources, holding at bay many infectious diseases that would otherwise sicken and kill millions. It is imperative we do all we can to preserve the effectiveness of those that remain, and give ourselves more options by working to discover and develop new ones.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213460/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christine Carson receives funding from state and federal funding agencies, and the CUREator program, a national biotechnology incubator delivered by Brandon BioCatalyst. She has a commercial interest in companies developing diagnostic tests and preventing viral infections.</span></em></p>We’ve all heard of antibiotic resistance. The same thing is happening with other causes of infections in humans: fungi, viruses and parasites. This is making thrush and other infections hard to treat.Christine Carson, Senior Research Fellow, School of Medicine, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2139812023-11-20T19:00:17Z2023-11-20T19:00:17ZNo, antibiotics aren’t always needed. Here’s how GPs can avoid overprescribing<figure><img src="https://images.theconversation.com/files/559257/original/file-20231114-26-vqpic.jpg?ixlib=rb-1.1.0&rect=718%2C370%2C6543%2C4463&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/candid-shot-black-female-doctor-explaining-2281209513">Shutterstock</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
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<p>The growth in antibiotic resistance threatens to return the world to the pre-antibiotic era – with deaths from now-treatable infections, and some elective surgery being restricted because of the risks of infection. </p>
<p>Antibiotic resistance is a major problem worldwide and should be the concern of everyone, including you. </p>
<p>We need to develop new antibiotics that can fight the resistant bacteria or antibiotics that bacteria would not be quickly resistant to. This is like finding new weapons to help the immune system fight the bacteria.</p>
<p>More importantly, we need to use our current antibiotics – our existing weapons against the bacteria – more wisely.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/could-new-antibiotic-clovibactin-beat-superbugs-or-will-it-join-the-long-list-of-failed-drugs-212774">Could new antibiotic clovibactin beat superbugs? Or will it join the long list of failed drugs?</a>
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</p>
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<h2>Giving GPs the tools to say no</h2>
<p>In 2022, more than <a href="https://www.safetyandquality.gov.au/publications-and-resources/resource-library/aura-2023-fifth-australian-report-antimicrobial-use-and-resistance-human-health">one-third of Australians</a> had least one antibiotic prescription, with <a href="https://www.safetyandquality.gov.au/publications-and-resources/resource-library/analysis-2015-2022-pbs-and-rpbs-antimicrobial-dispensing-data">88%</a> of antibiotics prescribed by GPs.</p>
<p>Many people <a href="https://pubmed.ncbi.nlm.nih.gov/28289114/">mistakenly think</a> antibiotics are necessary for treating any infection and that infections won’t improve unless treated with antibiotics. This misconception is found in studies involving patients with various conditions, including respiratory infections and conjunctivitis. </p>
<p>In reality, not all infections require antibiotics, and this belief drives patients requesting antibiotics from GPs. </p>
<p>Other times, GPs give antibiotics because they think patients want them, even when they might not be necessary. Although, in reality they are <a href="https://pubmed.ncbi.nlm.nih.gov/17148626/">after symptom relief</a>. </p>
<p>For GPs, there are ways to target antibiotics for only when they are clearly needed, even with short appointments with patients perceived to want antibiotics. This includes:</p>
<ul>
<li><p>using <a href="https://pubmed.ncbi.nlm.nih.gov/32357226/">decision guides</a> or tests to decide if antibiotics are really necessary</p></li>
<li><p>giving <a href="https://www.safetyandquality.gov.au/our-work/partnering-consumers/shared-decision-making/decision-support-tools-specific-conditions">patients information sheets</a> when antibiotics aren’t needed</p></li>
<li><p>giving a “<a href="https://pubmed.ncbi.nlm.nih.gov/33910882/">delayed prescription</a>” – only to be used after the patient waits to see if they get better on their own. </p></li>
</ul>
<p>All these strategies need some <a href="https://www.nps.org.au/assets/NPS/pdf/NPS-MedicineWise-Economic-evaluation-report-Reducing-Antibiotic-Resistance-2012-17.pdf">training</a> and practice, but they can help GPs prescribe antibiotics more responsibly. GPs can also learn from each other and use tools like <a href="https://pubmed.ncbi.nlm.nih.gov/24474434/">posters</a> as reminders.</p>
<p>To help with patients’ expectations, public campaigns have been run periodically to educate people about antibiotics. These campaigns <a href="https://pubmed.ncbi.nlm.nih.gov/35098267/">explain why</a> using antibiotics too much can be harmful and when it’s essential to take them.</p>
<h2>Giving doctors feedback on their prescribing</h2>
<p>National programs and interventions can help GPs use antibiotics more wisely </p>
<p>One successful way they do this is by <a href="https://pubmed.ncbi.nlm.nih.gov/34356788/">giving GPs feedback</a> about how they prescribe antibiotics. This works better when it’s provided by organisations that GPs trust, it happens more than once and clear goals are set for improvement. </p>
<figure class="align-center ">
<img alt="GP types on laptop" src="https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/559258/original/file-20231114-21-ou0m9a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">GPs tend to act on feedback about their antibiotic prescribing.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-entering-patient-notes-on-laptop-1033147024">Shutterstock</a></span>
</figcaption>
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<p>The NPS (formerly National Prescribing Service) MedicineWise program, for example, had been giving feedback to GPs on how their antibiotic prescriptions compared to others. This reduced the number of antibiotics prescribed. </p>
<p>However, <a href="https://australianprescriber.tg.org.au/articles/the-end-of-nps-medicinewise.html">NPS no longer exists</a>. </p>
<p>In 2017, the Australian health department did something similar by sending <a href="https://behaviouraleconomics.pmc.gov.au/projects/nudge-vs-superbugs-behavioural-economics-trial-reduce-overprescribing-antibiotics">feedback letters</a>, randomly using different formats, to the GPs who prescribed the most antibiotics, showing them how they were prescribing compared to others. </p>
<p>The most effective letter, which used pictures to show this comparison, reduced the number of antibiotics GPs prescribed by <a href="https://behaviouraleconomics.pmc.gov.au/sites/default/files/projects/nudge-vs-superbugs-12-months-on-report.pdf">9% in a year</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
</strong>
</em>
</p>
<hr>
<h2>Clearer rules and regulations</h2>
<p>Rules and regulations are crucial in the fight against antibiotic resistance. </p>
<p>Before April 2020, many GPs’ computer systems made it easy to get multiple repeat prescriptions for the same condition, which could encourage their overuse. </p>
<p>However, in April 2020, the Pharmaceutical Benefits Scheme (PBS) <a href="https://www.pbs.gov.au/pbs/industry/listing/elements/pbac-meetings/psd/2019-08/antibiotic-repeats-on-the-pharmaceutical-benefits-scheme">changed the rules</a> to ensure GPs had to think more carefully about whether patients actually needed repeat antibiotics. This meant the amount of medicine prescribed better matched the days it was needed for. </p>
<figure class="align-center ">
<img alt="Pharmacist looks at antibiotics" src="https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/559259/original/file-20231114-27-txxbfg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=474&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Simple changes can make a difference to antibiotic prescribing and dispensing.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmacist-holding-medicine-box-capsule-pack-704036482">Shutterstock</a></span>
</figcaption>
</figure>
<p>Other regulations or policy targets could include: </p>
<ul>
<li><p>ensuring all GPs have access to antibiotic prescribing guidelines, such as <a href="https://www.tg.org.au/">Therapeutic Guidelines</a>, which is well accepted and widely available in Australia</p></li>
<li><p>ensuring GPs are only prescribing antibiotics when needed. Many of the conditions antibiotics are currently prescribed for (such as sore throat, cough and middle ear infections) are self-limiting, meaning they will get better without antibiotics </p></li>
<li><p>encouraging GP working with antibiotics manufacturers to align pack sizes to the recommended treatment duration. The recommended first-line treatments for uncomplicated urinary tract infections in non-pregnant women, for example, are either three days of trimethoprim 300 mg per night or five days of nitrofurantoin 100 mg every six hours. However, the packs contain enough for seven days. This can mean patients take it for longer or use leftovers later. </p></li>
</ul>
<h2>Australia lags behind Sweden</h2>
<p>Australia has some good strategies for antibiotic prescribing, but we have not had a sustained long-term plan to ensure wise use. </p>
<p>Although Australian GPs have been doing well in <a href="https://www.safetyandquality.gov.au/our-work/antimicrobial-resistance/antimicrobial-use-and-resistance-australia-surveillance-system/aura-2021">reducing antibiotic prescribing</a> since 2015, <a href="https://pubmed.ncbi.nlm.nih.gov/35098269/">more</a> could be done. </p>
<p>In the 1990s, Sweden’s antibiotic use was similar to Australia’s, but is now less than half. For more than two decades, Sweden has had a national strategy that reduces antibiotic use by about <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677604/">7% annually</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-can-reverse-antibiotic-resistance-in-australia-heres-how-sweden-is-doing-it-123081">We can reverse antibiotic resistance in Australia. Here's how Sweden is doing it</a>
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<p>It is vital Australia invests in a similar long-term national strategy – to have a centrally funded program, but with regional groups working on the implementation. This could be funded directly by the Commonwealth Department of Health and Ageing, or with earmarked funds via another body such as the Australian Centre for Disease Control. </p>
<p>In the meantime, individual GPs can do their part to prescribe antibiotics better, and patients can join the national effort to combat antibiotic resistance by asking their GP: “what would happen if I don’t take an antibiotic?”. </p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>. Listen to the podcast <a href="https://theconversation.com/antibiotic-resistance-microbiologists-turn-to-new-technologies-in-the-hunt-for-solutions-podcast-217615">here</a>.</em></p><img src="https://counter.theconversation.com/content/213981/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mina Bakhit received funding from Therapeutic Guidelines Ltd (TGL) / Royal Australian College of General Practitioners (RACGP) Foundation Research Grant. </span></em></p><p class="fine-print"><em><span>Paul Glasziou receives funding from an National Health and Medical Research Council (NHMCR) Investigator grant.</span></em></p>Developing new antibiotics is important in the fight against antibiotic resistance. But we also need to use the antibiotics we already have much more wisely – GPs play a major role in this.Mina Bakhit, Assistant Professor of Public Health, Bond UniversityPaul Glasziou, Professor of Medicine, Bond UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2176152023-11-16T11:46:35Z2023-11-16T11:46:35ZAntibiotic resistance: microbiologists turn to new technologies in the hunt for solutions – podcast<figure><img src="https://images.theconversation.com/files/559597/original/file-20231115-23-wi1i4s.jpg?ixlib=rb-1.1.0&rect=6%2C78%2C4001%2C2506&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Testing for antimicrobial resistance in the lab.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-media-plate-on-hand-medical-507859600">AnaLysiSStudiO via Shutterstock</a></span></figcaption></figure><p>The rise of drug-resistant infections is one of the <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">biggest global threats</a> to health, food security and development. Antibiotic-resistant superbugs were estimated to kill <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">1.27 million people</a> in 2019, and the UN projects that drug-resistant diseases could <a href="https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis">cause 10 million deaths a year by 2050</a>. </p>
<p>In this episode of <a href="https://theconversation.com/uk/topics/the-conversation-weekly-98901">The Conversation Weekly</a> podcast, we hear from a microbiologist at a hospital in Nigeria working on the frontlines against antibiotic resistance, and find out about the new scientific techniques, including artificial intelligence (AI), being deployed to find new potential antibiotics.</p>
<iframe src="https://embed.acast.com/60087127b9687759d637bade/6555f7bb1cc403001252d7aa" frameborder="0" width="100%" height="190px"></iframe>
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<p><iframe id="tc-infographic-561" class="tc-infographic" height="100" src="https://cdn.theconversation.com/infographics/561/4fbbd099d631750693d02bac632430b71b37cd5f/site/index.html" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>Nubwa Medugu began her medical career in 2008 working in a paediatric unit in Kano, northern Nigeria. A lot of the children had typhoid and had taken antibiotics for it, but had come to hospital because the drugs weren’t working. “The fact that a lot of patients have infections that are very difficult to treat, I didn’t know it was just the tip of the iceberg then,” she says. </p>
<p>Today, Medugu is a clinical microbiologist at the National Hospital Abuja in Nigeria’s capital, and also teaches microbiology at Nile University of Nigeria. Her work involves analysing the hospital’s lab results for drug-resistant infections, and “the problem seems to have gotten worse”. She says it’s now “almost impossible” to find infections that are not resistant to at least one antibiotic. </p>
<p>Medugu recently <a href="https://www.nature.com/articles/s41598-023-37621-z">published research</a> analysing the level of antibiotic resistance in hospitals in Nigeria, and the types of antibiotics that are proving least effective. What’s most worrying is the number of infections that are resistant even to antibiotics of last resort – those drugs used to treat cases where other antibiotics have failed. “If nothing works, carbapenems usually work, but in this research, resistance to the carbapenems was pretty high … over 60% resistant.”</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
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<hr>
<h2>The hunt for new antibiotics</h2>
<p>Inequality and poverty are a big part of the problem. If people aren’t able to access vaccinations, diagnostic testing, medical advice and the right drugs if they’re infected, this can exacerbate antibiotic resistance. But even in a world where everybody had access to the healthcare they needed, bacteria would still develop resistance to antibiotics. </p>
<p>And so, as the problem deepens, the hunt continues on for new antibiotics. One of the scientists doing that searching is André Hudson, a professor of biochemistry at Rochester Institute of Technology in New York. He uses traditional bio-prospecting techniques to culture potential antibiotics from natural samples such as soil. But Hudson explains that others are now using new techniques to find potential antibiotic compounds. </p>
<blockquote>
<p>With AI, it allows it to go faster. It provides us with things that we cannot even think about, or we don’t even know how to do yet in the lab.</p>
</blockquote>
<p>Another approach is called <a href="https://www.nature.com/articles/455481a">metagenomics</a>, which involves sequencing an entire community of bacteria found in an environmental sample, such as soil or even the <a href="https://theconversation.com/we-found-more-than-54-000-viruses-in-peoples-poo-and-92-were-previously-unknown-to-science-163258">human gut</a>. “Rather than cherry-picking a particular bacteria, I extract all DNA that is present in the soil and sequence the entire community,” explains Hudson. </p>
<p>In September, a group of scientists in Germany, the Netherlands and the US published a paper announcing they’d discovered a potential antibiotic using this method called <a href="https://theconversation.com/could-new-antibiotic-clovibactin-beat-superbugs-or-will-it-join-the-long-list-of-failed-drugs-212774">clovibactin, isolated from uncultured soil bacteria</a>. </p>
<p>Find out more about the fight against antibiotic resistance, and the solutions on the cards, by listening to the full episode of <a href="https://podfollow.com/the-conversation-weekly/view">The Conversation Weekly</a>. A transcript is <a href="https://cdn.theconversation.com/static_files/files/2972/Antibiotic_Resistance_Transcript.docx.pdf?1701940198">now available</a>. </p>
<p>And read more about this topic in a special series, <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">The dangers of antibiotic resistance</a>, in which experts explore how we got here and the potential solutions.</p>
<hr>
<p><em>This episode was written and produced by Mend Mariwany and Gemma Ware with assistance from Katie Flood. Eloise Stevens does our sound design, and our theme music is by Neeta Sarl. Gemma Ware is the executive producer of the show.</em></p>
<p><em>You can find us on X, formerly known as Twitter <a href="https://twitter.com/TC_Audio">@TC_Audio</a>, on Instagram at <a href="https://www.instagram.com/theconversationdotcom/">theconversationdotcom</a> or <a href="mailto:podcast@theconversation.com">via email</a>. You can also subscribe to The Conversation’s <a href="https://theconversation.com/newsletter">free daily email here</a>.</em></p>
<p><em>Listen to <em>The Conversation Weekly</em> via any of the apps listed above, download it directly via our <a href="https://feeds.acast.com/public/shows/60087127b9687759d637bade">RSS feed</a> or find out <a href="https://theconversation.com/how-to-listen-to-the-conversations-podcasts-154131">how else to listen here</a>.</em></p><img src="https://counter.theconversation.com/content/217615/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>André O. Hudson receives funding from the National Institutes of Health. Nubwa Medugu does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>From the frontline battle against antibiotic resistance in Nigeria, to the techniques being used to find new antibiotics. Listen to The Conversation Weekly podcast.Gemma Ware, Editor and Co-Host, The Conversation Weekly Podcast, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2128742023-11-08T19:10:33Z2023-11-08T19:10:33ZDo you think you have a penicillin allergy? You might be wrong<figure><img src="https://images.theconversation.com/files/555945/original/file-20231025-19-tbp1oy.jpg?ixlib=rb-1.1.0&rect=98%2C160%2C8144%2C5326&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/these-all-possible-causes-shot-young-2148946861">Shutterstock</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">experts explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>Penicillins are the most prescribed class of antibiotics in Australia. Originally derived from a fungus, penicillin antibiotics such as amoxicillin are used to treat common infections, including chest, sinus, ear, urinary tract and skin infections. </p>
<p>Penicillins are effective against a wide range of bacteria that cause common infections. But their activity is not so broad as to impact on good bacteria in our gut like other antibiotic classes do. They’re also cheap and readily accessible.</p>
<p>Up to <a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376#bib1">20%</a> of Australians admitted in hospital say they have a penicillin allergy.</p>
<p>But not everyone who thinks they’re allergic to penicillin actually is. Research from <a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376?via%3Dihub">our team</a> and others suggests that if we assess all these patients, up to 90% are not allergic to it.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/weekly-dose-penicillin-the-mould-that-saves-millions-of-lives-63770">Weekly Dose: penicillin, the mould that saves millions of lives</a>
</strong>
</em>
</p>
<hr>
<h2>Why does it matter?</h2>
<p>People who mistakenly think they’re allergic to penicillin may not get the most effective or safest antibiotics to treat their infection. </p>
<p>They are also at greater risk of developing <a href="https://www.sciencedirect.com/science/article/abs/pii/S009167491301467X">multidrug-resistant infections</a> or “superbugs”. This is because the antibiotic will kill off the bacteria that are susceptible to it, but the resistant bacteria are left behind to proliferate and cause further infection.</p>
<p>People who receive second-line antibiotics are more likely to have complications, such as <a href="https://www.sciencedirect.com/science/article/abs/pii/S009167491301467X">antibiotic-induced gut infections</a>. Second-line antibiotics tend to have a wider range of activity, killing both the bacteria causing infection, and the good bacteria required to keep our gut in balance. This allows bugs like <em>Clostridium difficile</em>, which normally lives in our gut but is controlled by other bacteria, to overgrow and cause inflammation. </p>
<p>For the health system, using second-line antibiotics means longer, more complicated hospital stays. Hospital stays for patients with penicillin allergies cost up to <a href="https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2222.2003.01638.x">63% more</a> more than those without. It also results in greater costs for medications and greater resources required to treat the patient. </p>
<h2>Why do people think they’re allergic?</h2>
<p>People incorrectly believe they are allergic to penicillin for a number of reasons. </p>
<p>They may have experienced side effects from penicillin, such as nausea or diarrhoea. But though unpleasant, this doesn’t mean an allergy.</p>
<p>Others had a rash as a child, but this could have been due to the illness itself or an interaction between the virus and the antibiotic. An Epstein-Barr viral infection treated with amoxicillin, for example, <a href="https://pubmed.ncbi.nlm.nih.gov/23589810/">causes</a> a fine, red rash. </p>
<figure class="align-center ">
<img alt="Woman sits it wheelchair in hospital" src="https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555944/original/file-20231025-23-83c11.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It’s important to know your true allergy status when you go to hospital.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/rear-view-senior-asian-woman-sitting-1605865573">Shutterstock</a></span>
</figcaption>
</figure>
<p>Some believe a family history of reactions to penicillin means they cannot take them. But there is no evidence penicillin allergy is inherited. </p>
<p>If some time has passed between exposure, people can lose the allergic response. This is typically seen in adults who had a mild allergy as a child, but lose the response with time, so are said to have “grown out” of their allergy.</p>
<p>Then there are people who have had a genuine and serious reaction to penicillin. This includes anaphylaxis, with profound swelling, breathing difficulties and low blood pressure, and severe life-threatening reactions such as <a href="https://www.ncbi.nlm.nih.gov/books/NBK459323/#:%7E:text=Stevens%2DJohnson%20syndrome%2Ftoxic%20epidermal,in%20over%2080%25%20of%20cases.">Steven-Johnson’s syndrome</a>, which causes widespread blisters and wounds that resemble burns.</p>
<h2>Testing for penicillin</h2>
<p>When someone says they have a penicillin allergy, we first get them to explain what happened with the reaction, including to what antibiotic, in what context and how severe it was. </p>
<p>Then we perform skin tests to further assess the person’s risk of reaction. If skin tests are negative, we can then give the patient the penicillin in question under supervision (a “challenge”) to see if they react. </p>
<figure class="align-center ">
<img alt="Allergist performs skin test on patient's arm" src="https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/555946/original/file-20231025-27-q72zcu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Skin tests assess a patient’s reaction to the allergen.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/allergy-skin-prick-tests-184605983">Shutterstock</a></span>
</figcaption>
</figure>
<p>Some people can skip the skin tests altogether and go straight to the challenge if the history tells us they are at low risk of reacting.</p>
<p><a href="https://www.sciencedirect.com/science/article/pii/S2772829322000376?via%3Dihub">Our study</a> followed 195 patients who reported a penicillin allergy across six Sydney hospitals. In the first phase, we assessed 85 people and found 82% weren’t allergic to penicillin. </p>
<p>In the second phase, we assessed 110 people, of whom 69% weren’t allergic.
This is slightly lower than research on the population as a whole, because we only looked at people who were referred for an allergy assessment. Many more patients carry an allergy label than those referred for testing.</p>
<p>In our study, eight weeks after their test, just 54% of participants in phase one correctly knew their penicillin allergy status. Some allergic people believed they were not allergic, and many non-allergic people believed they were allergic.</p>
<p>For phase two, we ensured people received a standardised letter outlining their results in addition to having a doctor or nurse explain them. This time, 92% were correct in their understanding when contacted eight weeks later. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>Reducing long waits for allergy tests</h2>
<p>Ruling out allergies among people who think they can’t have penicillin is time- and labour-intensive. The wait time from someone first being referred to an allergy clinic to having testing can be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026071/">up to two years</a>. And it’s usually not available outside major metropolitan hospitals. </p>
<p>We need to improve access to testing and also look at <em>when</em> people can access allergy services. When a person is sick in hospital with a serious infection, it’s not the right time for testing.</p>
<p>We also need to ensure the results of allergy tests translate to the real world so people know their true allergy status. The fragmentation of our medical records are a barrier to clear and effective communication of a patient’s true allergy status, and urgently need to be improved.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/212874/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Winnie Tong has received funding from Maridulu Budyari Gumal, the Sydney Partnership for Health, Education, Research and Enterprise (SPHERE), Triple I Clinical Academic Group seed grant 2017, and the Balnaves Foundation. The authors would like to acknowledge Professor Andrew Carr, their collaborators and participants on this project. </span></em></p><p class="fine-print"><em><span>Jacqueline Loprete does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Up to 20% of Australians admitted in hospital say they have a penicillin allergy. But not everyone who thinks they’re allergic to penicillin actually is.Winnie Tong, Clinical Immunologist & Allergist, Immunopathologist and Senior Lecturer, UNSW SydneyJacqueline Loprete, Postdoctoral fellow, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134502023-11-07T19:35:17Z2023-11-07T19:35:17ZThe rise and fall of antibiotics. What would a post-antibiotic world look like?<figure><img src="https://images.theconversation.com/files/554665/original/file-20231019-25-r60wx5.jpg?ixlib=rb-1.1.0&rect=11%2C449%2C3982%2C2461&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-blue-and-white-polo-shirt-standing-on-yellow-flower-field-during-daytime-CEFYNiM9xLk">Luke Jones/Unsplash</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>These days, we don’t think much about being able to access a course of antibiotics to head off an infection. But that wasn’t always the case – antibiotics have been available for less than a century. </p>
<p>Before that, patients would die of relatively trivial infections that became more serious. Some serious infections, such as those involving the heart valves, were <a href="https://pubmed.ncbi.nlm.nih.gov/20173297/">inevitably</a> fatal. </p>
<p>Other serious infections, such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070694/">tuberculosis</a>, weren’t always fatal. Up to a <a href="https://www.biorxiv.org/content/10.1101/729426v1.full.pdf">half</a> of people died within a year with the most severe forms, but some people recovered without treatment and the remainder had ongoing chronic infection that slowly ate away at the body over many years. </p>
<p>Once we had antibiotics, the outcomes for these infections were much better.</p>
<h2>Life (and death) before antibiotics</h2>
<p>You’ve probably heard of Alexander Fleming’s accidental <a href="https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html">discovery of penicillin</a>, when fungal spores landed on a plate with bacteria left over a long weekend in 1928. </p>
<p>But the <a href="https://www.ox.ac.uk/news/science-blog/penicillin-oxford-story">first patient</a> to receive penicillin was an instructive example of the impact of treatment.
In 1941, Constable Albert Alexander had a scratch on his face that had become infected. </p>
<p>He was hospitalised but despite various treatments, the infection progressed to involve his head. This required removing one of his eyes.</p>
<figure class="align-center ">
<img alt="Old hospital room" src="https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554667/original/file-20231019-29-4a4qra.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">In 1941, Albert Alexander was hospitalised with a severe infection.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/furniture-and-fixtures-in-a-hospital-room-13083355/">Jonathan Borba/Pexels</a></span>
</figcaption>
</figure>
<p>Howard Florey, the Australian pharmacologist then working in Oxford, was concerned penicillin could be toxic in humans. Therefore, he felt it was only ethical to give this new drug to a patient in a desperate condition. </p>
<p>Constable Alexander was given the available dose of penicillin. Within the first day, his condition had started to improve. </p>
<p>But back then, penicillin was difficult to produce. One way of extending the limited supply was to “recycle” penicillin that was excreted in the patient’s urine. Despite this, supplies ran out by the fifth day of Alexander’s treatment. </p>
<p>Without further treatment, the infection again took hold. Constable Alexander eventually died a month later.</p>
<p>We now face a world where we are potentially running out of antibiotics – not because of difficulties manufacturing them, but because they’re losing their effectiveness.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<h2>What do we use antibiotics for?</h2>
<p>We currently use antibiotics in humans and animals for a variety of reasons. Antibiotics reduce the duration of illness and the chance of death from infection. They also prevent infections in people who are at high risk, such as patients undergoing surgery and those with weakened immune systems. </p>
<p>But antibiotics aren’t always used appropriately. <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30084-0/fulltext">Studies</a> consistently show a dose or two will adequately prevent infections after surgery, but antibiotics are <a href="https://irp.cdn-website.com/d820f98f/files/uploaded/surgical-prophylaxis-prescribing-in-australian-hospitals-results-of-the-2020-surgical-national-antimicrobial-prescribing-survey.pdf">often</a> continued for several days unnecessarily. And sometimes we use the wrong type of antibiotic. </p>
<p><a href="https://irp.cdn-website.com/d820f98f/files/uploaded/antimicrobial-prescribing-practice-in-australian-hospitals-results-of-the-2020-hospital-national-antimicrobial-prescribing-survey.pdf">Surveys</a> have found 22% of antimicrobial use in hospitals is inappropriate. </p>
<figure class="align-center ">
<img alt="Pharmacist looks at label on medicine box" src="https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554669/original/file-20231019-23-xes5p9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibiotics are used for longer than needed and sometimes the wrong type is used.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-white-dress-shirt-and-black-pants-standing-near-brown-wooden-shelf-fTQHPb6r4wQ">National Cancer Institute/Unsplash</a></span>
</figcaption>
</figure>
<p>In some situations, this is understandable. Infections in different body sites are usually due to different types of bacteria. When the diagnosis isn’t certain, we often <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/resp.13334">err</a> on the side of caution by giving broad spectrum antibiotics to make sure we have active treatments for all possible infections, until further information becomes available.</p>
<p>In other situations, there is a degree of inertia. If the patient is improving, doctors tend to simply continue the same treatment, rather than change to more appropriate choice. </p>
<p>In general practice, the issue of diagnostic uncertainty and therapeutic inertia are often magnified. Patients who recover after starting antibiotics don’t usually require tests or come back for review, so there is no easy way of knowing if the antibiotic was actually required. </p>
<p>Antibiotic prescribing can be more complex again if <a href="https://www.mja.com.au/journal/2014/201/2/antibiotic-prescribing-practice-residential-aged-care-facilities-health-care">patients</a> are expecting “a pill for every ill”. While doctors are generally good at educating patients when antibiotics are not likely to work (for example, for viral infections), without confirmatory tests there can always be a lingering doubt in the minds of both doctors and patients. Or sometimes the patient goes elsewhere to find a prescription. </p>
<p>For other infections, resistance can develop if treatments aren’t given for long enough. This is particularly the <a href="https://pubmed.ncbi.nlm.nih.gov/11971765/">case</a> for tuberculosis, caused by a slow growing bacterium that requires a particularly long course of antibiotics to cure. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/tuberculosis-isnt-just-a-historical-disease-heres-how-it-spreads-and-who-is-at-risk-215154">Tuberculosis isn't just a historical disease. Here's how it spreads and who is at risk</a>
</strong>
</em>
</p>
<hr>
<p>As in humans, antibiotics are also used to prevent and treat infections in animals. However, a proportion of antibiotics are used for growth promotion. In Australia, an <a href="https://www.mja.com.au/journal/2019/211/4/antibiotic-use-animals-and-humans-australia">estimated</a> 60% of antibiotics were used in animals between 2005-2010, despite growth-promotion being phased out.</p>
<h2>Why is overuse a problem?</h2>
<p>Bacteria become resistant to the effect of antibiotics through natural selection – those that survive exposure to antibiotics are the strains that have a mechanism to evade their effects. </p>
<p>For example, antibiotics are sometimes given to <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30279-2/fulltext">prevent</a> recurrent urinary tract infections, but a consequence, any infection that does <a href="https://academic.oup.com/cid/article/73/3/e782/6141409">develop</a> tends to be with resistant bacteria.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rising-antibiotic-resistance-in-utis-could-cost-australia-1-6-billion-a-year-by-2030-heres-how-to-curb-it-149543">Rising antibiotic resistance in UTIs could cost Australia $1.6 billion a year by 2030. Here's how to curb it</a>
</strong>
</em>
</p>
<hr>
<p>When resistance to the commonly used first-line antibiotics occurs, we often need to reach deeper into the bag to find other effective treatments. </p>
<p>Some of these last-line antibiotics are those that had been <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202707/">superseded</a> because they had serious side effects or couldn’t be given conveniently as tablets. </p>
<p>New drugs for some bacteria have been developed, but many are much more <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955006/">expensive</a> than older ones. </p>
<h2>Treating antibiotics as a valuable resource</h2>
<p>The concept of antibiotics as a valuable resource has led to the <a href="https://pubmed.ncbi.nlm.nih.gov/8856755/">concept</a> of “antimicrobial stewardship”, with programs to promote the responsible use of antibiotics. It’s a similar concept to environmental stewardship to prevent climate change and environmental degradation. </p>
<p>Antibiotics are a rare class of medication where treatment of one patient can potentially affect the outcome of other patients, through the transmission of antibiotic resistant bacteria. Therefore, like efforts to combat climate change, antibiotic stewardship relies on changing individual actions to benefit the broader community.</p>
<figure class="align-center ">
<img alt="Surgeon ties her mask" src="https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554670/original/file-20231019-27-9skfki.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antimicrobial stewardship relies on individuals making decisions for the greater good.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/woman-in-teal-shirt-wearing-white-mask-8hHxO3iYuU0">SJ Objio/Unsplash</a></span>
</figcaption>
</figure>
<p>Like climate change, antibiotic resistance is a complex problem when seen in a broader context. Studies have linked resistance to the values and priorities <a href="https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(18)30186-4/fulltext">of governments</a> such as corruption and infrastructure, including the availability of electricity and public services. This highlights that there are broader “causes of the causes”, such as public spending on sanitation and health care. </p>
<p>Other <a href="https://academic.oup.com/jac/article/74/9/2803/5512029?login=true">studies</a> have suggested individuals need to be considered within the broader social and institutional influences on prescribing behaviour. Like all human behaviour, antibiotic prescribing is complicated, and factors like what doctors feel is “normal” prescribing, whether junior staff feel they can challenge senior doctors, and even their <a href="https://www.nytimes.com/2016/10/07/upshot/your-surgeon-is-probably-a-republican-your-psychiatrist-probably-a-democrat.html">political views</a> may be important. </p>
<p>There are also issues with the <a href="https://www.cambridge.org/core/journals/international-journal-of-technology-assessment-in-health-care/article/value-assessment-of-antimicrobials-and-the-implications-for-development-access-and-funding-of-effective-treatments-australian-stakeholder-perspective/D45758CFB95520DA4FF06E46135E0628">economic model</a> for developing new antibiotics. When a new antibiotic is first approved for use, the first reaction for prescribers is not to use it, whether to ensure it retains its effectiveness or because it is often very expensive. </p>
<p>However, this doesn’t really <a href="https://academic.oup.com/cid/article/50/8/1081/449089?login=true">encourage</a> the development of new antibiotics, particularly when pharma research and development budgets can easily be diverted to developing drugs for conditions patients take for years, rather than a few days. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-need-to-change-how-antibiotics-target-bugs-if-we-want-them-to-keep-working-183135">We need to change how antibiotics target bugs if we want them to keep working</a>
</strong>
</em>
</p>
<hr>
<h2>The slow moving pandemic of resistance</h2>
<blockquote>
<p>If we fail to act, we are looking at an almost unthinkable scenario where antibiotics no longer work and we are cast back into the dark ages of medicine
– <a href="https://amr-review.org/">David Cameron</a>, former UK Prime Minister </p>
</blockquote>
<p>Antibiotic resistance is already a problem. Almost all infectious diseases physicians have had the dreaded call about patients with infections that were essentially untreatable, or where they had to scramble to find supplies of long-forgotten last-line antibiotics. </p>
<p>There are already hospitals in some parts of the world that have had to carefully <a href="https://www.reactgroup.org/news-and-views/news-and-opinions/year-2022/the-impact-of-antibiotic-resistance-on-cancer-treatment-especially-in-low-and-middle-income-countries-and-the-way-forward/">consider</a> whether it’s still viable to treat cancers, because of the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276316/">high risk</a> of infections with antibiotic-resistant bacteria. </p>
<p>A global <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">study</a> estimated that in 2019, almost 5 million deaths occurred with an infection involving antibiotic-resistant bacteria. Some 1.3 million would not have occurred if the bacteria were not resistant. </p>
<p>The UK’s 2014 <a href="https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf">O'Neill report</a> predicted deaths from antimicrobial resistance could rise to 10 million deaths each year, and cost 2-3.5% of global GDP, by 2050 based on trends at that time. </p>
<h2>What can we do about it?</h2>
<p>There is a lot we can do to prevent antibiotic resistance. We can:</p>
<ul>
<li><p><a href="https://www.marketingmag.com.au/news/film-picking-gonorrhoea-wins-tropfest-prize/">raise</a> <a href="https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-019-7258-3">awareness</a> that many infections will get better by themselves, and don’t necessarily need antibiotics </p></li>
<li><p>use the antibiotics we have more appropriately and for as short a time as possible, supported by co-ordinated clinical and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437704/">public policy</a>, and <a href="https://www.amr.gov.au/">national</a> <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00796-4/fulltext">oversight</a> </p></li>
<li><p><a href="https://www.safetyandquality.gov.au/our-work/antimicrobial-resistance/antimicrobial-use-and-resistance-australia-surveillance-system/about-aura-surveillance-system">monitor</a> for infections due to resistant bacterial to inform control policies </p></li>
<li><p>reduce the inappropriate use of antibiotics in animals, such as <a href="https://nam.edu/antibiotic-resistance-in-humans-and-animals/">growth promotion</a> </p></li>
<li><p><a href="https://pubmed.ncbi.nlm.nih.gov/11971765/">reduce</a> cross-transmission of resistant organisms in hospitals and in the community </p></li>
<li><p>prevent infections by other means, such as clean water, <a href="https://apps.who.int/iris/bitstream/handle/10665/204948/WHO_FWC_WSH_14.7_eng.pdf">sanitation</a>, hygiene and <a href="https://www.who.int/teams/immunization-vaccines-and-biologicals/product-and-delivery-research/anti-microbial-resistance">vaccines</a> </p></li>
<li><p>continue developing new antibiotics and alternatives to antibiotics and ensure the right <a href="https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(23)00124-2/fulltext#:%7E:text=We%20consider%20four%20incentive%20options,exclusivity%20extensions%2C%20and%20milestone%20payments.">incentives</a> are in place to encourage a continuous pipeline of new drugs.</p></li>
</ul>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213450/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Allen Cheng receives funding from the Australian Government and the National Health and Medical Research Council. He is affiliated with the Centre to Impact Antimicrobial Resistance at Monash University. </span></em></p>Antibiotics have been around for less than a century. But as resistant bacteria become increasingly difficult to treat, we risk a greater number of deaths from infections.Allen Cheng, Professor of Infectious Diseases, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2134512023-11-07T19:35:15Z2023-11-07T19:35:15ZHow do bacteria actually become resistant to antibiotics?<figure><img src="https://images.theconversation.com/files/555508/original/file-20231024-24-2win4c.jpg?ixlib=rb-1.1.0&rect=0%2C817%2C5928%2C3745&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/a-person-holding-a-round-object-in-their-hands-y--8fqaK1kY">CDC/Unsplash</a></span></figcaption></figure><p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
<hr>
<p>“What doesn’t kill me makes me stronger”, originally coined by <a href="https://www.dictionary.com/e/slang/what-doesnt-kill-you-makes-you-stronger/">Friedrich Nietzsche in 1888</a>, is a perfect description of how bacteria develop <a href="https://www.nps.org.au/consumers/antibiotics-explained#what-is-antibiotic-resistance?">antibiotic resistance</a>. </p>
<p>Contrary to a common belief, antibiotic resistance <a href="https://www.cdc.gov/antibiotic-use/images/Infographic-AR-bacteria.jpg">is not</a> about your body becoming resistant to antibiotics. </p>
<p>Resistance arises when bacteria are exposed to levels of antibiotics that don’t immediately kill them. They develop defences that prevent the same antibiotic from harming them in the future, even at higher doses.</p>
<h2>How bacteria adapt</h2>
<p>The ability for bacteria to adapt lies in part with their astonishing rate of reproduction. Some species, such as <em>Escherichia coli</em>, can <a href="https://www.youtube.com/watch?v=gEwzDydciWc">replicate</a> as quickly as every 20 minutes, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015860/">depending on the environment</a>. One bacterium can become more than 68 billion bacteria in 12 hours.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/im-a-microbiologist-and-heres-what-and-where-i-never-eat-213404">I'm a microbiologist and here's what (and where) I never eat</a>
</strong>
</em>
</p>
<hr>
<p>However, bacteria don’t faithfully reproduce their genetic code, and mutations can slip in every generation. </p>
<p>While most changes are bad, sometimes they can help the bacteria grow in the presence of an antibiotic. This “new and improved” population <a href="https://www.cdc.gov/antibiotic-use/images/Infographic-how-AR-happens.jpg">quickly takes over</a>.</p>
<p>Additional mutations enable survival at even higher antibiotic concentrations.</p>
<p>This evolution of resistance can be seen by growing bacteria on a large agar plate (a nutrient support that bacteria like to grow on) with zones of increasing antibiotic levels. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/plVk4NVIUh8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Watch how bacteria develop resistance to extremely high concentrations of antibiotics (Harvard Medical School).</span></figcaption>
</figure>
<p>Growth is halted when they first encounter the next zone, but once they have developed resistance they quickly expand until they reach the next region with more antibiotic. </p>
<p>Bacteria in your body can easily develop resistance in a similar manner during the typical seven- to ten-day course of antibiotic treatment.</p>
<h2>They also exchange genetic material</h2>
<p>The other key mechanism enabling bacterial resistance is the <a href="https://www.cdc.gov/drugresistance/pdf/threats-report/How-AR-Moves-508.pdf">exchange of genetic information</a> between bacteria. </p>
<p>In addition to the main chunk of DNA that encodes the bacterial genome, bacteria can host circular DNA snippets called plasmids. These plasmids are <a href="https://asm.org/Articles/2023/January/Plasmids-and-the-Spread-of-Antibiotic-Resistance-G">readily exchanged between bacteria</a>, including different species.</p>
<p>Plasmid exchange usually occurs by direct physical contact between bacteria. Bacteria are promiscuous, so this can happen a lot! Once inside a bacteria, plasmids can be passed down to the next generation. </p>
<p>Unfortunately, plasmids are <a href="https://www.annualreviews.org/doi/10.1146/annurev.biochem.78.082907.145923?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed">particularly good</a> at encoding multiple resistance genes.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/rising-antibiotic-resistance-in-utis-could-cost-australia-1-6-billion-a-year-by-2030-heres-how-to-curb-it-149543">Rising antibiotic resistance in UTIs could cost Australia $1.6 billion a year by 2030. Here's how to curb it</a>
</strong>
</em>
</p>
<hr>
<h2>4 ways bacteria resist</h2>
<p>Bacteria develop resistance to antibiotic treatment using four main methods:</p>
<p><strong>1) Keep the antibiotic out.</strong> Bacteria are good at keeping unwanted molecules from getting inside. </p>
<p>Gram-positive bacteria like <em>Staphylococcus aureus</em> have a thick cell wall enclosing a lipid membrane. Gram-negative bacteria, such as <em>E. coli</em>, are more difficult to kill as they have an additional outer membrane that acts as an extra barrier. </p>
<p>Bacteria are able to bring in the things they need to survive through these cell surfaces. Antibiotics can hijack these entry routes, but bacteria can modify the cell wall, cell membrane and entry proteins to block antibiotic penetration.</p>
<p>For example, bacteria <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149586/">increase the thickness</a> of the cell wall to resist antibiotics like vancomycin.</p>
<figure class="align-center ">
<img alt="Lab worker puts dropper into petri dish" src="https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554684/original/file-20231019-21-kwo9mt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bacteria are good at keeping antibiotics out.</span>
<span class="attribution"><a class="source" href="https://www.pexels.com/photo/man-doing-a-sample-test-in-the-laboratory-4033148/">Edward Jenner/Pexels</a></span>
</figcaption>
</figure>
<p><strong>2. Expel the antibiotic if it gets in</strong>. Bacteria have machinery known as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032748/">efflux pumps</a>, which regurgitate unwanted molecules from within the bacteria. </p>
<p>Bacteria can alter the pump so it is more effective at removing the antibiotic, or they can simply make more pumps. </p>
<p>Resistance to macrolide antibiotics like erythromycin often involves <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1251515/">the production of more efflux pumps</a>.</p>
<p><strong>3) Alter the antibiotic target.</strong> Antibiotics, like most other drugs, generally work by blocking the function of important enzymes within the bacteria. They specifically bind to the target like a key in a lock. </p>
<p>If bacteria alter the target shape by changing the DNA/protein sequence, the antibiotic (key) can no longer bind to its target (lock). </p>
<p>Resistance to a class of antibiotics known as fluoroquinolones (which includes ciprofloxacin) often occurs due to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1114060/">mutations of the enzyme targets</a>.</p>
<p><strong>4) Destroy or modify the antibiotic.</strong> Bacteria developed resistance to the original antibiotic, penicillin, by producing a protein that breaks apart the penicillin warhead. </p>
<p>These enzymes have evolved to keep pace with even the most recent new and improved penicillin-like antibiotics. </p>
<p>In response, drug developers <a href="https://www.drugs.com/drug-class/beta-lactamase-inhibitors.html">have created</a> molecules that specifically stop the enzyme from working, and dose these in combination with the antibiotic. </p>
<p>Another example of antibiotic modification is shown by resistance to a class of antibiotics called aminoglycosides. In this case, different types of enzymes <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752126/">chemically modify</a> the structure of the aminoglycoside, such as the antibiotic tobramycin. Now, the key has been filed so that it no longer fits the lock.</p>
<figure class="align-center ">
<img alt="Person holds three antibiotic capsules" src="https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/554681/original/file-20231019-27-o3qlqf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Bacteria use multiple methods to attack antibiotics.</span>
<span class="attribution"><a class="source" href="https://unsplash.com/photos/three-capsules-on-persons-palm-U31rRVKYL_M">Mark Fletcher/Unsplash</a></span>
</figcaption>
</figure>
<h2>Bacteria vs antibiotics</h2>
<p>While bacteria have developed mechanisms to resist antibiotics, these adaptations can come at a “fitness” cost. Bacteria may grow more slowly, or can be killed more easily by another antibiotic. </p>
<p>This has led to the concept of “<a href="https://academic.oup.com/mbe/article/39/12/msac257/6884036">collateral sensitivity</a>” to prevent or overcome resistance when treating patients, by using pairs of antibiotics. Resistance to the first antibiotic increases susceptibility to the second, and vice versa.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
</strong>
</em>
</p>
<hr>
<p>In some cases, the “fitness costs” (energy and materials expended to maintain resistance) mean that resistance genes can be present, but they are not activated until exposed to an antibiotic. This makes it difficult to predict bacterial resistance by just looking at their genetic makeup. </p>
<p>Bacteria may get “stronger,” but they are not yet invincible. We need to take action before antibiotic resistance returns us to a pre-antibiotic era.</p>
<hr>
<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213451/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Blaskovich receives funding from a range of government, not-for-profit and commercial organisations for research into antibiotic discovery and development. He is affiliated with AAMRNet (Australian Antimicrobial Resistance Network), an organisation promoting improved care and development of antibiotics and antibiotic alternatives.</span></em></p>Resistance arises when bacteria are exposed to levels of antibiotics that don’t immediately kill them. Here’s how.Mark Blaskovich, Professor, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2160802023-11-01T05:20:48Z2023-11-01T05:20:48ZBioprospecting the unknown: how bacterial enzymes encoded by unknown genes might help clean up pollution<p>Enzymes are biological nanomachines. They make almost all of life’s chemistry happen, when and where required.</p>
<p>Because of their versatility and power, enzymes can be very useful for biotechnology. Taken outside of living cells, they can be used to synthesise or modify pharmaceuticals or to degrade potential pollutants.</p>
<p>Bacteria contain genes that encode an unfathomable range of enzymes. However, scientists have barely scratched the surface of this potential because 99% of bacteria cannot be grown in laboratory conditions, and hence are largely unstudied. </p>
<p>My team has addressed this by treating the entirety of bacterial DNA in soil – representing thousands of bacterial species – as “genetic software”. </p>
<p>In our <a href="https://www.cell.com/cell-chemical-biology/pdf/S2451-9456(23)00337-9.pdf">new research</a> we show how we can transfer this software to laboratory bacterial strains and then screen for desirable new functions and isolate the enzymes responsible.</p>
<h2>Discovering new enzymes</h2>
<p>For more than a century, scientists have been collecting soil samples and culturing bacteria, then finding uses for enzymes the bacteria produce. However, when sophisticated DNA-sequencing technologies were developed around the turn of the millennium, it became apparent that standard culturing methods were missing most of the bacteria present. </p>
<p>These technologies showed that a gram of soil, from which typically fewer than 100 different microbial species can be cultured, actually contains many thousands.</p>
<p>The same DNA-sequencing technologies have revealed that the hard-to-grow bacteria contain large numbers of genes whose function is entirely unknown. We are discovering that some of these mystery genes can help us address major problems.</p>
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<img alt="A petri Petri-dish with a a green bacterium growing in the shape of New Zealand, surrounded by _E. coli_ bacteria containing an extra gene that encodes an enzyme to make a blue pigment." src="https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=557&fit=crop&dpr=1 600w, https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=557&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=557&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=700&fit=crop&dpr=1 754w, https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=700&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/556498/original/file-20231030-21-w23k9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=700&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Petri-dish ‘agar art’: green <em>Pseudomonas aeruginosa</em> bacteria in an ocean of <em>E. coli</em> containing an extra gene that encodes an enzyme to make a blue pigment.</span>
<span class="attribution"><span class="source">Mark Calcott</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
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<p>Genes are really just passive units of information – pieces of software code within the hard drive of a living cell. But when that information is activated, the outcome is the production of proteins. Most of these are enzymes. </p>
<p>These enzymes then act as nanoscale catalysts for the chemistry that happens in a living cell. Here the software analogy struggles somewhat, as life is biological, not digital - which means it’s noisy and messy.</p>
<p>Thus, an enzyme might perform a primary job that makes an obvious contribution to a cell’s wellbeing. But it might also be capable of doing a dozen other minor things that may or may not have any obvious value. </p>
<p>Those minor “moonlighting” roles are very important for evolution. A function that has no importance today could turn out to be essential in the future, when an entirely new stress arises. </p>
<p>My team is interested in leveraging the evolutionary potential of “unknown unknown” enzymes from soil-dwelling bacteria to solve important problems. To achieve this, we are partnering with Te Herenga Waka’s <a href="https://www.wgtn.ac.nz/living-pa">Living Pā</a> team to discover new enzymes from soil samples, collected on site with their permission.</p>
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Read more:
<a href="https://theconversation.com/electricity-from-thin-air-an-enzyme-from-bacteria-can-extract-energy-from-hydrogen-in-the-atmosphere-200432">Electricity from thin air: an enzyme from bacteria can extract energy from hydrogen in the atmosphere</a>
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<h2>Using enzymes to tackle problems</h2>
<p>One of the unfortunate consequences of evolution is that bacteria frequently contain enzymes that can provide low levels of protection against new antibiotics developed to fight disease. If those antibiotics are overused, or used inappropriately, the bacteria might start to promote the protective function. This is how full-on antibiotic resistance evolves. </p>
<p>This is a very real problem. Every year <a href="https://www.bbc.com/news/health-60058120">millions of people die of bacterial infections</a> that used to be treatable, but no longer are. My team has been studying <a href="https://www.newsroom.co.nz/ideasroom/a-moonlighting-challenge-to-antibiotics">how bacterial resistance to promising new antibiotics can arise</a>, so countermeasures can be put in place before it’s too late.</p>
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Read more:
<a href="https://theconversation.com/will-we-still-have-antibiotics-in-50-years-we-asked-7-global-experts-214950">Will we still have antibiotics in 50 years? We asked 7 global experts</a>
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<p>But we are also interested in how unknown enzymes encoded by unknown genes might be directly useful – or evolve to be useful – for applications that protect and preserve the environment. For example, enzymes are being discovered and evolved to enable more <a href="https://www.theguardian.com/environment/2023/sep/28/plastic-eating-bacteria-enzyme-recycling-waste">effective recycling of plastics</a> or <a href="https://www.bbc.com/future/article/20231016-cleaning-up-pfas-forever-chemicals">remediate persistent environmental pollutants</a>.</p>
<p>Our latest work represents a breakthrough in developing new methods to study the many millions of unknown genes that can be extracted from dirt samples. </p>
<p>Our approach starts by extracting all of the bacterial DNA present in soil and breaking it into bite-sized pieces that contain just one or two genes. We then place them in a special carrier system that allows them to be introduced into a tame laboratory bacterium called <em>Escherichia coli</em>. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1718009826519790076"}"></div></p>
<p>Our innovation lies with how we access the information within the newly introduced genes, which is not immediately easy to do. By way of analogy, we all know that Android software usually won’t work on Apple operating systems. Imagine if there were not just a few incompatible operating systems, but many thousands. That’s the problem we face. </p>
<p>We have booted up a commonly used laboratory bacterial strain (<em>E. coli</em>) with new software that would usually be entirely incompatible. But we have developed a universally applicable emulator that allows <em>E. coli</em> to run most of the new software going into it. </p>
<p>We can then screen for individual <em>E. coli</em> bacteria that have gained new properties of interest to us – for example, degradation of target pollutants. Although the enzymes responsible for these new activities might not initially be very efficient, mimicking natural evolutionary processes within the lab environment can improve a low-grade starting activity to an industrially useful level.</p>
<p>Because enzymes are non-living, biodegradable and cannot in any way replicate themselves, they offer safe and controlled solutions to a vast array of problems – if we can find ones able to get the job done.</p><img src="https://counter.theconversation.com/content/216080/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David Ackerley does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Bacterial DNA extracted from soil includes many genes whose function remains unknown. The novel enzymes these genes code for could be useful in efforts to clean up persistent pollutants.David Ackerley, Professor of Biotechnology, Te Herenga Waka — Victoria University of WellingtonLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2149502023-10-15T19:09:36Z2023-10-15T19:09:36ZWill we still have antibiotics in 50 years? We asked 7 global experts<figure><img src="https://images.theconversation.com/files/551987/original/file-20231004-23-73liu8.jpg?ixlib=rb-1.1.0&rect=0%2C5%2C3889%2C2584&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Almost since antibiotics were <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2937522/#:%7E:text=Since%20the%20introduction%20in%201937,operate%20some%2070%20years%20later.">first discovered</a>, we’ve been aware bacteria can learn how to overcome these medicines, a phenomenon known as antimicrobial resistance.</p>
<p>The World Health Organization says we’re currently <a href="https://www.who.int/news/item/20-09-2017-the-world-is-running-out-of-antibiotics-who-report-confirms">losing to the bugs</a>, with resistance increasing and too few new antibiotics in the pipeline. </p>
<p>We wanted to know whether experts around the world think we will still have effective antibiotics in 50 years. Seven out of seven experts said yes.</p>
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<img alt="Seven green tick marks in a row" src="https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=99&fit=crop&dpr=1 600w, https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=99&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=99&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=125&fit=crop&dpr=1 754w, https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=125&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/552217/original/file-20231005-19-g8ovop.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=125&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<p class="fine-print"><em><span>André O. Hudson receives funding from the National Institutes of Health.</span></em></p><p class="fine-print"><em><span>Lori L. Burrows receives research grants from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, Glyconet, and the Ontario Research Fund.</span></em></p><p class="fine-print"><em><span>Roy Robins-Browne has received funding from The Australian National Health and Medical Research Council, The Australian Research Council, the Bill and Melinda Gates Research Foundation and The US National Institutes of Health.</span></em></p><p class="fine-print"><em><span>Fidelma Fitzpatrick, Juliana Côrrea, Raúl Rivas González, and Yori Yuliandra do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>We asked 7 global experts in microbiology and biochemistry if we are headed towards a future with no antimicrobial agents.André O. Hudson, Dean of the College of Science, Professor of Biochemistry, Rochester Institute of TechnologyFidelma Fitzpatrick, Consultant Microbiologist, Beaumont Hospital, Dublin, Ireland and Professor and Head of Department, Clinical Microbiology, RCSI University of Medicine and Health SciencesJuliana Côrrea, Pesquisadora de pós-doutorado em saúde pública, Escola de Administração de Empresas de São Paulo da Fundação Getúlio Vargas (FGV/EAESP)Lori L. Burrows, Professor of Biocchemistry and Biomedical Sciences, McMaster UniversityRaúl Rivas González, Catedrático de Microbiología. Miembro de la Sociedad Española de Microbiología., Universidad de SalamancaRoy Robins-Browne, Honorary Professorial Fellow, medical microbiology, The University of MelbourneYori Yuliandra, Associate Professor of Pharmaceutical Sciences, Universitas AndalasLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2112492023-08-10T14:03:22Z2023-08-10T14:03:22ZAir pollution linked with global rise in antibiotic resistance<figure><img src="https://images.theconversation.com/files/542157/original/file-20230810-27-qfmzoe.jpg?ixlib=rb-1.1.0&rect=8%2C0%2C5377%2C3229&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Air pollution is linked with many health problems.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/vehicles-people-moving-streets-amidst-heavy-780429076">Saurav022/ Shutterstock</a></span></figcaption></figure><p>Antibiotic resistance is a growing threat to global health. In 2019, it caused over <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">1.27 million deaths worldwide</a> – and it’s projected that antimicrobial resistance (which includes bacterial resistance to antibiotics) may contribute to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127510/">ten million deaths</a> per year by 2050.</p>
<p>Antibiotics are used to treat bacterial infections such as urinary tract infections and pneumonia. But their <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">misuse and overuse</a> has contributed to the emergence of bacteria which harbour genes that enable them to withstand the killing power of antibiotics. This results in infections that are much harder to treat. </p>
<p>Antibiotic resistance mainly spreads to humans through <a href="https://www.cdc.gov/foodsafety/challenges/antibiotic-resistance.html">contaminated food or water</a>. But a <a href="https://www.thelancet.com/action/showPdf?pii=S2542-5196%2823%2900135-3">recent study</a> suggests this isn’t the only way resistant bacteria can spread. According to researchers from China and the UK, air pollution may also be spreading antibiotic resistance.</p>
<p>This is the first study to comprehensively estimate the link between increased antibiotic resistance and air pollution globally. </p>
<h2>The burden of air pollution</h2>
<p>The review analysed the findings of previous studies that looked at patterns of the airborne spread of antibiotic resistance over nearly two decades. They looked at 12 research studies conducted across 116 countries – including the UK, US, China, India and Australia. These studies estimated the emergence of antibiotic resistant bacteria or genes in the atmosphere.</p>
<p>The study looked specifically at the most dangerous type of air pollution – <a href="https://www.indoorairhygiene.org/pm2-5-explained/">PM2.5</a>. This is particulate matter that has a diameter of 2.5 micrometres – about 3% the diameter of a strand of human hair. PM2.5 cannot be seen by the naked eye and can easily be inhaled.</p>
<p>The study found that antibiotic resistance rose alongside increasing PM2.5 concentrations in the air. Every 10% rise in the concentration of PM2.5 was linked with a 1.1% global increase in antibiotic resistance and 43,654 deaths from antibiotic-resistant bacterial infections. </p>
<p>The study reported that the highest levels of antibiotic resistance were seen in north Africa and west Asia. These areas also had the most severe PM2.5 pollution. In comparison, Europe and North America – which had the lowest average levels of PM2.5 pollution – also had lower levels of antibiotic resistance.</p>
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<img alt="A bottle of polymixin antibiotics." src="https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/542159/original/file-20230810-19-beo9f2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Polymixins are the last resort antibiotic.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/active-substance-polymyxin-b-sulfate-antibiotic-2319447537">luchschenF/ Shutterstock</a></span>
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<p>The study also reported that even just a 1% increase in PM2.5 across all regions was associated with an increase in <em>Klebsiella pneumoniae</em> resistance to multiple antibiotics – including <a href="https://pubmed.ncbi.nlm.nih.gov/34475315/#:%7E:text=Polymyxins%2C%20the%20cationic%20lipopeptide%20antibiotics,effect%20against%20Gram%2Dnegative%20bacteria">polymyxins</a>, which are the last resort of antibiotics. This bacterium typically spreads in hospitals and can cause pneumonia, meningitis and urinary tract infections. </p>
<p>Although <em>Klebsiella</em> is not spread via the air, this suggests that air pollution may also make it easier for resistant bacteria to thrive and spread <a href="https://www.cdc.gov/hai/organisms/klebsiella/klebsiella.html#:%7E:text=In%20healthcare%20settings%2C%20Klebsiella%20bacteria%20can%20be%20spread,The%20bacteria%20are%20not%20spread%20through%20the%20air">in the environment</a>.</p>
<p>The study shows there’s a significant relationship between air pollution and antibiotic resistance. Although the authors didn’t show evidence of causation between the two factors, they did find antibiotic resistance genes in the DNA of bacteria sequenced from air samples. This indicates that PM2.5 could facilitate the spread of antibiotic resistant bacteria and genes via the air.</p>
<h2>Spread of resistance</h2>
<p>This isn’t the first study to show a link between air pollution and antibiotic resistance.</p>
<p>Air pollution has also been shown to be a risk factor for tuberculosis caused by the bacterium <em><a href="https://academic.oup.com/femsre/article/41/3/354/3089982">Mycobacterium tuberculosis</a></em>. This bacterium has developed resistance to multiple antibiotics. </p>
<p>A study in Hong Kong also revealed an association between outdoor <a href="https://pubmed.ncbi.nlm.nih.gov/27595179/">exposure to PM2.5 and tuberculosis</a>. The study found an increase in PM2.5 concentrations during the winter was associated with a 3% increase in the number of tuberculosis cases the following spring and summer.</p>
<p>However, it’s still unclear what underlying mechanisms may allow antibiotic resistance to spread in air pollution. It will be important for future studies to investigate this.</p>
<p>We do know from this study and others that PM2.5 can harbour antibiotic resistant bacteria or genes that can enter the human body through the <a href="https://www.sciencedirect.com/science/article/pii/S0160412019339625#:%7E:text=However%2C%20in%20addition%20to%20chemical%20properties%2C%20biological%20components,respiratory%20system%2C%20causing%20lung%20damage%20and%20respiratory%20infections">respiratory system</a> when <a href="https://www.frontiersin.org/articles/10.3389/fmicb.2019.00054/full">we breathe</a>. </p>
<p>We also know from previous studies that <a href="https://www.sciencedirect.com/science/article/abs/pii/S1352231016303855">antibiotic resistant bacteria</a> and their genes can be transmitted from one person to another through the air via respiratory droplets. Sneezing, coughing and even talking can all emit respiratory droplets. It’s also possible that a person who has inhaled antibiotic resistant bacteria from air pollution could then pass these on to another person when they cough or sneeze.</p>
<p>Environmental changes caused by air pollution (such as increased temperature and humidity) may also make it <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189961/#:%7E:text=The%20relative%20humidity%20or%20relative%20water%20content%20of,viable%20longer%20in%20association%20with%20high%20relative%20humidity">easier for resistant bacteria to thrive</a>. But again, it will be important for researchers to conduct studies looking into whether this is the case.</p>
<p>It will also be important for researchers to investigate the role of other factors (other than PM2.5) that can contribute to antibiotic resistance. For example, exposure to pollutants, the foods we eat, the use of antibiotics for animals and environmental disasters. </p>
<p>While we may not know exactly how air pollution helps spread antibiotic resistance, the link between the two is clear. Air pollution is also associated with a range of other health conditions – including <a href="https://www.epa.gov/air-research/air-pollution-and-cardiovascular-disease-basics#:%7E:text=Research%20by%20EPA%20and%20others,and%20decreases%20in%20life%20expectancy">cardiovascular disease</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001082/">asthma</a>, poorer <a href="https://jtd.amegroups.org/article/view/6353/html#:%7E:text=They%20concluded%20that%20the%20overall,occupation%20and%20other%20risk%20factors">lung function</a> and greater <a href="https://www.ochsnerjournal.org/content/19/1/4">risk of depression</a>. </p>
<p>Given the many harms air pollution already has to our health, this study only further strengthens arguments to urgently <a href="https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health#:%7E:text=Policies%20and%20investments%20supporting%20cleaner%20transport%2C%20energy%20efficient,greatly%20reduce%20ambient%20air%20pollution%20in%20some%20regions">improve air quality</a> and reduce pollution globally.</p><img src="https://counter.theconversation.com/content/211249/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Manal Mohammed does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Antibiotic resistance can affect anyone of any age.Manal Mohammed, Senior Lecturer, Medical Microbiology, University of WestminsterLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2098452023-07-18T19:06:09Z2023-07-18T19:06:09ZAntibiotic-resistant bacteria in NZ’s wild cockles and watercress put people at growing risk of serious illness<figure><img src="https://images.theconversation.com/files/537937/original/file-20230718-27-svvszk.jpg?ixlib=rb-1.1.0&rect=12%2C233%2C4093%2C2468&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock/Philip Armitage</span></span></figcaption></figure><p>Traditional harvesting sites, or mahinga kai, continue to be used throughout New Zealand to provide food and to share skills and cultural practices between families and generations.</p>
<p>But our new <a href="https://www.sciencedirect.com/science/article/pii/S0269749123011570?via%3Dihub">research</a> shows that wild foods concentrate antibiotic-resistant bacteria and could put people at risk.</p>
<p>While water is regularly tested at recreational sites for potential pathogens, wild-harvested foods are commonly overlooked as a source of exposure to antibiotic-resistant microbes. </p>
<p>Wild foods are important to all cultures in Aotearoa. Both aquatic and terrestrial mahinga kai sites provide opportunities for recreation and social bonding. Entire regions may come to rely more heavily on wild foods during disasters that disrupt supply chains.</p>
<p>But there are no guidelines for people who harvest wild foods to inform them about the risk of antibiotic resistance. This needs to change. </p>
<p>Antibiotic-resistant bacteria make gastrointestinal infections from eating wild foods or contact infections acquired during harvest or food preparation more difficult, even impossible, to treat.</p>
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Read more:
<a href="https://theconversation.com/humans-are-polluting-the-environment-with-antibiotic-resistant-bacteria-and-im-finding-them-everywhere-150744">Humans are polluting the environment with antibiotic-resistant bacteria, and I'm finding them everywhere</a>
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<h2>The creeping pandemic of antibiotic resistance</h2>
<p><a href="https://www.pmcsa.ac.nz/topics/antimicrobial-resistance-and-infectious-disease/">Antibiotic resistance</a> is one of the <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">biggest threats</a> to global health and food security, according to the World Health Organization.</p>
<p>It occurs when bacteria become less responsive to the antibiotics used to prevent or treat bacterial infections. Over time, populations within any species of bacteria emerge with one, then two or more resistances to antibiotics, until we get potentially untreatable super strains. </p>
<p>This process is happening in all bacteria, pathogenic or benign, leading to super strains that are resistant to multiple antibiotics.</p>
<p>Because of the way antibiotic resistance genes clump together, super strains are usually super spreaders of antibiotic resistance. </p>
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Read more:
<a href="https://theconversation.com/we-know-why-bacteria-become-resistant-to-antibiotics-but-how-does-this-actually-happen-59891">We know _why_ bacteria become resistant to antibiotics, but _how_ does this actually happen?</a>
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<p>Bacteria are linked together in a horizontal gene-sharing network. Genes can transfer between members of the same and different species at high frequency. So no matter in which species the resistant gene first appears, it can potentially be transferred to a pathogen.</p>
<h2><em>E. coli</em> on watercress and in mussels and cockles</h2>
<p>In conjunction with the local hapū <a href="https://ngaitahu.iwi.nz/te-runanga-o-ngai-tahu/papatipu-runanga/ngai-tuahuriri/">Te Ngāi Tūāhuriri Rūnanga</a> and <a href="https://www.ecan.govt.nz/">Environment Canterbury</a>, we monitored waterways used to harvest kai (food) such as watercress. We found both rural and urban streams have high levels of <em>Escherichia coli</em>, a bacterium found in human or animal faeces and commonly identified <a href="https://www.lawa.org.nz/explore-data/swimming/">in freshwater and coastal environments</a> in Aotearoa.</p>
<p><em>E. coli</em> is used as an indicator for infection risk in water and food. In the sites we studied, concentrations of <em>E. coli</em> were consistently high over many years. These bacteria can cause diseases in their own right, but what makes them a good indicator is that they co-locate in the environment with other pathogenic bacteria and are easy to grow in the laboratory.</p>
<p>We identified <em>E. coli</em> on plants (watercress) and in animals (mussels and cockles) taken for kai. In some samples, up to 20% of the <em>E. coli</em> were resistant to the frontline antibiotic drug ampicillin. </p>
<p>This means infections by one in five <em>E. coli</em> might fail to respond to a frequently prescribed antibiotic, leading to more suffering or medical complications.</p>
<p>We also detected resistance to last-resort drugs such as ciprofloxacin. Ciprofloxacin is usually prescribed to treat bacterial infections when other antibiotics have already failed. Often, the bacteria we found were resistant to drug concentrations that exceeded what could be safely given to a patient.</p>
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<img alt="Hands holding a green-lipped mussel." src="https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/537949/original/file-20230718-21-l0wtv9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Bacteria concentrate in shellfish from the water they filter.</span>
<span class="attribution"><span class="source">Shutterstock/Mr Hendrix</span></span>
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<h2>Safe to touch does not equal safe to eat</h2>
<p>Another observation we made was that mahinga kai, particularly shellfish, concentrate bacteria from the water they filter. Large cockles can filter three litres per hour and this concentrating effect was so powerful that we found antibiotic-resistant bacteria in the cockles even when we couldn’t detect them in water samples.</p>
<p>Bacteria extracted from cockles were “ingested” during high tide and showed us what the water was like over that time period. In contrast, water samples, such as those used to inform swimming guidelines, represent only the conditions at the time of sampling. </p>
<p>This is important, because rainfall and sewage overflow events transiently increase the number of bacteria in water and may not be picked up during routine monitoring.</p>
<p>Our calculations suggest that existing water safety guidance does not apply to the risk of contracting an antibiotic-resistant infection and could mislead those harvesting wild foods into taking greater risks. </p>
<p>The shellfish in our study were collected from popular sites in Waitaha/Canterbury. Local government monitors these sites and provides guidance on swimming safety. Our work shows that swimming guidance does not substitute for making decisions about whether or not to harvest wild kai. </p>
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Read more:
<a href="https://theconversation.com/bacteria-shuffle-their-genetics-around-to-develop-antibiotic-resistance-on-demand-156439">Bacteria 'shuffle' their genetics around to develop antibiotic resistance on demand</a>
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<p>We need improved guidelines for the safe harvesting and use of wild foods and more strenuous monitoring to protect those who rely on mahinga kai. </p>
<p>To maintain the benefits of harvesting wild foods, we should take a <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9220317/">One Health</a> approach that formalises the links between medicine and the environment. It helps to prevent the cause – rather than just the symptoms – of infectious disease and antibiotic resistance.</p>
<p>The problem of contaminated water doesn’t end with aquatic mahinga kai. </p>
<p>These same waters can be used for drinking or irrigation. The climate is warming and resulting floods gather more contamination from cities and farms into waterways. </p>
<p>Mahinga kai sites are not just lifeboats in time of need. They are the canary telling us that we must change our ways.</p><img src="https://counter.theconversation.com/content/209845/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jack Heinemann has received funding from Brian Mason Trust, Marsden Fund, and various other government, civil society, philanthropic, and industry sources.</span></em></p><p class="fine-print"><em><span>Sophie Joy van Hamelsveld does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Our new research found up to 20% of bacteria in wild foods were resistant to a common antibiotic drug. Some samples had resistance to last-resort antibiotics, prescribed when other drugs have failed.Jack Heinemann, Professor of Molecular Biology and Genetics, University of CanterburySophie Joy van Hamelsveld, Postdoctoral Scientist, University of CanterburyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2060452023-07-05T12:23:01Z2023-07-05T12:23:01Z‘E. coli’ is one of the most widely studied organisms – and that may be a problem for both science and medicine<figure><img src="https://images.theconversation.com/files/534368/original/file-20230627-19-w2lrsx.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2133%2C1404&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">_E. coli_ as a model organism helped researchers better understand how DNA works.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/researcher-with-e-coli-bacteria-royalty-free-image/521677434">Ed Horowitz Photography/The Image Bank via Getty Images</a></span></figcaption></figure><p>In 1857, a young pediatrician named <a href="https://doi.org/10.1038/nrmicro1810">Theodor Escherich</a> discovered what may very well be the most well-studied organism today. The rod-shaped bacterium named <em>Escherichia coli</em>, better known as <em>E. coli</em>, is a very common microbe residing in your gut. It’s also the workhorse of early molecular biology.</p>
<p>Luck likely played a role in its rise in popularity among scientists. Even under 19th-century lab conditions, where sterilization techniques were not perfect and little was known about what food bacteria need to survive, this microbe was easy to cultivate and grow quickly. It can <a href="https://doi.org/10.1098/rspb.2018.0789">replicate in under 20 minutes</a> and can use a variety of <a href="https://doi.org/10.1186/s12918-014-0133-z">carbon sources for energy</a>. </p>
<p>As the first species to have its <a href="https://doi.org/10.1128/jb.29.2.205-213.1935">physiology thoroughly explored</a>, <em>E. coli</em> has contributed fundamental knowledge to the fields of microbiology, molecular genetics and biochemistry, including how DNA replicates, how genes create proteins and how bacteria share genetic material among themselves – a huge <a href="https://theconversation.com/antibiotic-resistance-is-at-a-crisis-point-government-support-for-academia-and-big-pharma-to-find-new-drugs-could-help-defeat-superbugs-169443">cause of antibiotic resistance</a>. </p>
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<a href="https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Diagram of E. coli structure" src="https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=365&fit=crop&dpr=1 600w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=365&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=365&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=458&fit=crop&dpr=1 754w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=458&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/534417/original/file-20230627-17-qy37yx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=458&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption"><em>E. coli</em> is a rod-shaped bacterium with flagella that help it move.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/coli-bacteria-micro-biological-vector-royalty-free-illustration/957344970">VectorMine/iStock via Getty Images Plus</a></span>
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<p>However, the favored use of <em>E. coli</em> in the lab has also <a href="https://doi.org/10.1529/biophysj.107.104398">led to oversimplifications</a> in the world of microbiology, distracting researchers from the thousands of other bacterial species that <a href="https://doi.org/10.1073/pnas.1707009114">remain understudied</a>. </p>
<p>As <a href="https://doerr.wicmb.cornell.edu/current-lab-members/">microbiologists</a> <a href="https://scholar.google.com/citations?user=yYroRg8AAAAJ&hl=en">studying the</a> inner mechanisms of <a href="https://theconversation.com/looming-behind-antibiotic-resistance-is-another-bacterial-threat-antibiotic-tolerance-200226">antibiotic tolerance</a>, we and colleagues in <a href="https://doerr.wicmb.cornell.edu/">our lab</a> examine bacterial species that physiologically differ from <em>E. coli</em> in hopes of expanding the existing pool of knowledge within microbiology. For instance, drugs like penicillin fall into a class of antibiotics that target the outer defenses of the bacteria. We found that while <em>E. coli</em> succumbs to this attack, species like <em>Vibrio</em> or <em>Klebsiella</em> can <a href="https://theconversation.com/looming-behind-antibiotic-resistance-is-another-bacterial-threat-antibiotic-tolerance-200226">tolerate it and survive</a>. </p>
<p>A one-size-fits-all approach may have worked in the past, but embracing the true diversity of microbes could help scientists better fight the rise of antibiotic resistance.</p>
<h2>Scientific good of <em>E. coli</em></h2>
<p>Researchers worked out the very foundations of life using <em>E. coli</em>. The significance of this bacterium for the field of biology is probably best captured by the biochemist <a href="https://www.nobelprize.org/prizes/medicine/1965/monod/facts/">Jacques Monod</a>, who famously said, “What is true for <em>E. coli</em> is true for the elephant.” </p>
<p>Because researchers were able to watch regions of <a href="https://doi.org/10.1038/158558a0"><em>E. coli</em>‘s DNA become mobile</a>, allowing bacteria to transfer DNA among one another in a process called conjugation, scientists learned to manipulate this process to genetically alter organisms and study the effects of different genes. </p>
<p><em>E. coli</em> helped reveal that <a href="https://doi.org/10.1101/SQB.1963.028.01.011">bacterial chromosomes are circular</a> and that <a href="https://doi.org/10.1016/S0022-2836(59)80045-0">manipulating a specific enzyme</a> can allow scientists to easily clone parts of the bacterial genome. </p>
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<span class="caption">While <em>E. coli</em> are common residents in your gut, certain strains can cause serious infections.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/coli-sem-royalty-free-image/1414386430">Steve Gschmeissner/Science Photo Library via Getty Images</a></span>
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<p><em>E. coli</em> also opened doors to using a type of <a href="https://theconversation.com/viruses-are-both-the-villains-and-heroes-of-life-as-we-know-it-169131">bacterial viruses called phages</a> as an <a href="https://doi.org/10.1085/jgp.22.3.365">alternative to antibiotics</a>. </p>
<p>Widely available knowledge about and methods to study <em>E. coli</em> led to its prominence in academic and commercial research and drug production. In 2015, <a href="https://doi.org/10.4014/jmb.1412.12079">nearly 30% of proteins used as treatments</a> for a wide range of diseases like hepatitis C and multiple sclerosis were derived from <em>E. coli</em>.</p>
<h2>Model organism drawbacks</h2>
<p><em>E. coli</em>’s track record has solidified its place in the lab as a <a href="https://doi.org/10.1007/978-1-4419-9863-7_76">model organism</a>. Model organisms are nonhuman species researchers use to study biology, with the expectation that the findings can be applied to other species like humans. Species are often chosen for their ease of maintenance, quick life cycles and overall cost-effectiveness. </p>
<p>However, model organisms have their drawbacks. Some researchers have argued that drawing parallels across species can <a href="https://theconversation.com/expanding-alzheimers-research-with-primates-could-overcome-the-problem-with-treatments-that-show-promise-in-mice-but-dont-help-humans-188207">sometimes fall short</a>, leading to assumptions about more complex species that may not be true.</p>
<p>Additionally, study findings using nonmodel organisms are often less visible in the broader scientific community, since many researchers focus on organisms with known and defined traits. This bias results in a shadow space where progress is not immediately incorporated into broader scientific knowledge, which can slow down research that actually covers a range from bacteria to elephants.</p>
<h2>ESKAPE pathogens don’t include <em>E. coli</em></h2>
<p>Model organisms are not perfect, and <em>E. coli</em> may not be an effective species to use to study many human bacterial infections. Focusing research on this microbe limits the exploration of how other bacteria infiltrate and infect human hosts. While some <a href="https://doi.org/10.1038/nrmicro818">strains of <em>E. coli</em> can be deadly</a>, they are not the only worrisome pathogens today. </p>
<p><a href="https://doi.org/10.1128/cmr.00181-19">ESKAPE pathogens</a>, a group of bacteria that are highly resistant to antibiotics, pose a massive global health threat because they can quickly evolve traits that allow them to evade immune systems and available treatments. Species within ESKAPE, such as <em>Klebsiella pneumoniae</em> and <em>E. cloacae</em>, are able to resist multiple drugs and <a href="https://doi.org/10.1128/aac.00756-19">exhibit physical characteristics</a> that <em>E. coli</em> does not, such as the ability to remove their cell wall and evade certain drugs.</p>
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<figcaption><span class="caption">Antibiotic-resistant bacteria are a major global health threat.</span></figcaption>
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<p>Our lab is studying the unique traits that allow ESKAPE pathogens to survive antibiotics – traits we would not have known about if we used only <em>E. coli</em> as a model organism in our research.</p>
<p>With the many basics of fundamental bacterial cell and molecular biology covered thanks to <em>E. coli</em>, it may be time for researchers to turn toward the new pathogens wreaking havoc on society. Model organisms are wondrous tools, but they have limited power to allow findings to be extrapolated to other organisms. Better understanding the underpinnings of bacterial infections and antibiotics for a given disease requires studying the specific organism.</p><img src="https://counter.theconversation.com/content/206045/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Keller receives funding from National Science Foundation. </span></em></p><p class="fine-print"><em><span>Tobias Dörr receives funding from National Institutes of Health. </span></em></p>Researchers uncovered the foundations of biology by using E. coli as a model organism. But over-reliance on this microbe can lead to knowledge blind spots with implications for antibiotic resistance.Megan Keller, Ph.D. Candidate in Microbiology, Cornell UniversityTobias Dörr, Associate Professor of Microbiology, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2069322023-06-04T11:19:08Z2023-06-04T11:19:08ZRemoving antimicrobial resistance from the WHO’s ‘pandemic treaty’ will leave humanity extremely vulnerable to future pandemics<figure><img src="https://images.theconversation.com/files/529846/original/file-20230602-27-nnu80l.png?ixlib=rb-1.1.0&rect=17%2C80%2C1680%2C1219&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antimicrobial resistance is now a leading cause of death worldwide due to drug-resistant infections, including drug-resistant strains of tuberculosis, pneumonia and Staph infections like the methicillin-resistant Staphylococcus aureus shown here.</span> <span class="attribution"><span class="source">(NIAID, cropped from original)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><iframe style="width: 100%; height: 100px; border: none; position: relative; z-index: 1;" allowtransparency="" allow="clipboard-read; clipboard-write" src="https://narrations.ad-auris.com/widget/the-conversation-canada/removing-antimicrobial-resistance-from-the-who-s--pandemic-treaty--will-leave-humanity-extremely-vulnerable-to-future-pandemics" width="100%" height="400"></iframe>
<p>In late May, the latest version of the draft Pandemic Instrument, also referred to as the “pandemic treaty,” was shared with Member States at the <a href="https://www.who.int/about/governance/world-health-assembly">World Health Assembly</a>. The text was made available online via <a href="https://healthpolicy-watch.news/wp-content/uploads/2023/05/DRAFT_INB_Bureau-text_22-May.pdf">Health Policy Watch</a> and it quickly became apparent that all mentions of addressing antimicrobial resistance in the Pandemic Instrument were at risk of removal.</p>
<p>Work on the Pandemic Instrument began in December 2021 after the World Health Assembly agreed to a global process to draft and negotiate an international instrument — under the Constitution of the World Health Organization (WHO) — to protect nations and communities from future pandemic emergencies.</p>
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Read more:
<a href="https://theconversation.com/drug-resistant-superbugs-a-global-threat-intensified-by-the-fight-against-coronavirus-135790">Drug-resistant superbugs: A global threat intensified by the fight against coronavirus</a>
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<p>Since the beginning of negotiations on the Pandemic Instrument, there have been calls from civil society and leading experts, including the <a href="https://www.amrleaders.org/docs/librariesprovider20/default-document-library/amr-as-substantive-element-of-the-international-instument-of-pandemic-prevention-preparedness-and-response.pdf?sfvrsn=300292c8_5&download=true">Global Leaders Group on Antimicrobial Resistance</a>, to include the so-called “silent” pandemic of antimicrobial resistance in the instrument.</p>
<p>Just three years after the onset of a global pandemic, it is understandable why Member States negotiating the Pandemic Instrument have focused on preventing pandemics that resemble COVID-19. But not all pandemics in the past have been caused by viruses and not all pandemics in the future will be caused by viruses. Devastating past pandemics of bacterial diseases have included <a href="https://www.who.int/news-room/fact-sheets/detail/plague">plague</a> and <a href="https://www.who.int/news-room/fact-sheets/detail/cholera">cholera</a>. The next pandemic could be caused by bacteria or other microbes.</p>
<h2>Antimicrobial resistance</h2>
<figure class="align-right ">
<img alt="Yellow particles on purple spikes" src="https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529862/original/file-20230602-19-rvxpbm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Microscopic view of Yersinia pestis, the bacteria that cause bubonic plague, on a flea. Plague is an example of previous devastating pandemics of bacterial disease.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Antimicrobial resistance (AMR) is the process by which infections caused by microbes become resistant to the medicines developed to treat them. Microbes include bacteria, fungi, viruses and parasites. Bacterial infections alone cause <a href="https://www.tropicalmedicine.ox.ac.uk/gram/news/bacterial-infections-linked-to-one-in-eight-global-deaths-according-to-gram-study">one in eight deaths</a> globally.</p>
<p>AMR is fueling the rise of drug-resistant infections, including <a href="https://www.cdc.gov/tb/publications/factsheets/drtb/xdrtb.htm">drug-resistant tuberculosis</a>, <a href="https://www.cdc.gov/drugresistance/pdf/threats-report/strep-pneumoniae-508.pdf">drug-resistant pneumonia</a> and drug-resistant Staph infections such as <a href="https://www.cdc.gov/mrsa/index.html">methicillin-resistant Staphylococcus aureus</a> (MRSA). These infections are killing and debilitating millions of people annually, and <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">AMR is now a leading cause of death worldwide</a>. </p>
<p>Without knowing what the next pandemic will be, the “pandemic treaty” must plan, prepare and develop effective tools to respond to a wider range of pandemic threats, not solely viruses.</p>
<p>Even if the world faces another viral pandemic, <a href="https://theconversation.com/when-covid-19-or-flu-viruses-kill-they-often-have-an-accomplice-bacterial-infections-187056">secondary bacterial infections</a> will be a serious issue. During the COVID-19 pandemic for instance, large percentages of those hospitalized with COVID-19 required treatment for secondary bacterial infections. </p>
<p>New research from Northwestern University suggests that many of the deaths among hospitalized COVID-19 patients <a href="https://news.feinberg.northwestern.edu/2023/05/05/secondary-bacterial-pneumonia-drove-many-covid-19-deaths/">were associated with pneumonia — a secondary bacterial infection that must be treated with antibiotics</a>. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="An illustrative diagram that shows the difference between a drug resistant bacteria and a non-resistant bacteria." src="https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=558&fit=crop&dpr=1 600w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=558&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=558&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=701&fit=crop&dpr=1 754w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=701&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/529852/original/file-20230602-29-ejrjyi.gif?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=701&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Antimicrobial resistance means infections that were once treatable are much more difficult to treat.</span>
<span class="attribution"><span class="source">(NIAID)</span>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Treating these bacterial infections requires effective antibiotics, and with AMR increasing, <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">effective antibiotics are becoming a scarce resource</a>. Essentially, safeguarding the remaining effective antibiotics we have is critical to responding to any pandemic.</p>
<p>That’s why the potential removal of measures that would help mitigate AMR and better safeguard antimicrobial effectiveness is so concerning. Sections of the text which may be removed include measures to prevent infections (caused by bacteria, viruses and other microbes), such as:</p>
<ul>
<li> better access to safe water, sanitation and hygiene; </li>
<li> higher standards of infection prevention and control; </li>
<li> integrated surveillance of infectious disease threats from human, animals and the environment; and </li>
<li> strengthening <a href="https://www.cdc.gov/antibiotic-use/core-elements/index.html">antimicrobial stewardship</a> efforts to optimize how antimicrobial drugs are used and prevent the development of AMR.</li>
</ul>
<p>The exclusion of these measures would hinder efforts to protect people from future pandemics, and appears to be part of a <a href="https://www.nature.com/articles/d41586-023-01805-4">broader shift to water-down the language in the Pandemic Instrument</a>, making it easier for countries to opt-out of taking recommended actions to prevent future pandemics. </p>
<h2>Making the ‘pandemic treaty’ more robust</h2>
<p>Measures to address AMR could be easily included and addressed in the “pandemic treaty.”</p>
<p>In September 2022, I was part of a group of civil society and research organizations that specialize in mitigating AMR who were invited the WHO’s <a href="https://inb.who.int/">Intergovernmental Negotiating Body</a> (INB) to provide an <a href="https://amrpolicy.org/resources/recommendations-to-the-intergovernmental-negotiating-body-inb-concerning-amr-the-pandemic-instrument/">analysis on how AMR should be addressed</a>, within the then-draft text. </p>
<p>They outlined that including bacterial pathogens in the definition of “pandemics” was critical. They also identified specific provisions that should be tweaked to track and address both viral and bacterial threats. These included AMR and recommended harmonizing national AMR stewardship rules.</p>
<p>In March 2023, I joined other leading academic researchers and experts from various fields in publishing a special edition of the <a href="https://www.cambridge.org/core/journals/journal-of-law-medicine-and-ethics/issue/DC40B54126C7B273BD62EBEED9641D2A"><em>Journal of Medicine, Law and Ethics</em>,</a> outlining why the Pandemic Instrument must address AMR. </p>
<p>The researchers of this special issue argued that the Pandemic Instrument was overly focused on viral threats and ignored AMR and bacterial threats, including the need to manage antibiotics as a common-pool resource and revitalize research and development of novel antimicrobial drugs. </p>
<h2>Next steps</h2>
<p>While <a href="https://apps.who.int/gb/inb/pdf_files/inb4/A_INB4_3-en.pdf">earlier drafts of the Pandemic Instrument</a> drew on guidance from AMR policy researchers and civil society organizations, after the first round of closed-door negotiations by Member States, all of these insertions, are now at risk for removal.</p>
<p>The Pandemic Instrument is the best option to mitigate AMR and safeguard lifesaving antimicrobials to treat secondary infections in pandemics. AMR exceeds the capacity of any single country or sector to solve. Global political action is needed to ensure the international community works together to collectively mitigate AMR and support the conservation, development and equitable distribution of safe and effective antimicrobials.</p>
<p>By missing this opportunity to address AMR and safeguard antimicrobials in the Pandemic Instrument, we severely undermine the broader goals of the instrument: to protect nations and communities from future pandemic emergencies.</p>
<p>It is important going forward that Member States recognize the core infrastructural role that antimicrobials play in pandemic response and strengthen, rather than weaken, measures meant to safeguard antimicrobials. </p>
<p>Antimicrobials are an essential resource for responding to pandemic emergencies that must be protected. If governments are serious about pandemic preparedness, they must support bold measures to conserve the effectiveness of antimicrobials within the Pandemic Instrument.</p><img src="https://counter.theconversation.com/content/206932/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Susan Rogers Van Katwyk is a member of the WHO Collaborating Centre on Global Governance of Antimicrobial Resistance at York University. She receives funding from the Wellcome Trust and the Social Sciences and Humanities Research Council of Canada. </span></em></p>Drug-resistant microbes are a serious threat for future pandemics, but the new draft of the WHO’s international pandemic agreement may not include provisions for antimicrobial resistance.Susan Rogers Van Katwyk, Adjunct Professor, School of Global Health and Managing Director, AMR Policy Accelerator, York University, CanadaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2020502023-05-24T13:43:06Z2023-05-24T13:43:06ZWastewater is a valuable source of information – Africa’s scientists need to use it to find drug-resistant bacteria<figure><img src="https://images.theconversation.com/files/526490/original/file-20230516-29-1kt7xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Sub-Saharan African countries don't have enough wastewater treatment plants. </span> <span class="attribution"><span class="source">John Wessels/AFP via Getty Images</span></span></figcaption></figure><p>People often think of wastewater as serving no purpose. But it can be a valuable source of information. Wastewater is increasingly <a href="https://www.sciencedirect.com/science/article/abs/pii/S2214714421006267">recognised</a> as a significant environmental reservoir for antimicrobial resistance – a growing global <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance#:%7E:text=What%20is%20antimicrobial%20resistance%3F,spread%2C%20severe%20illness%20and%20death.">public health threat</a>. </p>
<p>Antimicrobials are medicines, including antibiotics and antivirals, used to treat infections in humans, animals and plants. But the excessive use of antimicrobials has resulted in many microorganisms becoming resistant to these important medicines. This, in turn, has led to the development of complicated and sometimes untreatable diseases.</p>
<p>Antimicrobial resistance is expected to kill over <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">10 million</a> people annually by 2050 if nothing is done to stop it. In sub-Saharan Africa, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273632/">23.5 deaths out of every 100,000</a> are attributed to diseases such as lower respiratory, chest, bloodstream and intra-abdominal infection caused by antimicrobial-resistant organisms. </p>
<p>These organisms are all around us. For instance, <a href="https://pubmed.ncbi.nlm.nih.gov/33578692/">research</a> done on pigs in South Africa found resistant bacteria at all the stages of sampling, from the farm to the final packaged meat. Another South African <a href="https://www.frontiersin.org/articles/10.3389/fenvs.2021.751732/full">study</a> found that manure from a poultry farm transferred antibiotic-resistant bacteria to the soil. Heavy rainfall could wash these bacteria into nearby rivers. As a result, people who use water from these rivers for drinking and household purposes could get sick.</p>
<p>Wastewater treatment plants receive wastewater from a variety of sources: hospitals, households, industries and farms. This makes the plants useful proxies for determining the burden of antimicrobial resistance in communities. By monitoring wastewater, scientists can determine the types of resistant bacteria circulating in a given population. This approach is becoming the global gold standard for tracking antimicrobial resistance. </p>
<p>But it doesn’t seem to have been adopted in many African countries yet. Our <a href="https://www.mdpi.com/2079-6382/12/5/805">recent research</a> looked at studies done on wastewater in African countries between 2012 and 2022. We wanted to identify the challenges in using wastewater surveillance to determine the prevalence of antimicrobial resistance. </p>
<p>We found that using wastewater to study antimicrobial resistance was increasing on the continent. But not in all countries. In most of the studies we found samples were only collected once. This is not sufficient to draw strong conclusions. Furthermore, many studies used only one method to identify resistance in the wastewater. Depending on the method, this either overestimated or underestimated the rate of resistance. With these gaps, studies within the continent could be presenting a false picture of the antimicrobial resistance problem, which could have severe health implications. </p>
<h2>Case studies</h2>
<p>We <a href="https://www.mdpi.com/2079-6382/12/5/805">reviewed</a> studies on wastewater-based surveillance of antimicrobial resistance in sub-Saharan Africa. Our study showed that most countries lacked the necessary skills to conduct this research. The lack of skills affected the methods that the studies used, hence the results presented. </p>
<p>Most of the research was done in South Africa. That’s largely because most sub-Saharan countries simply do not have enough wastewater treatment plants. Many treat <a href="https://inweh.unu.edu/un-500-million-live-in-19-african-nations-deemed-water-insecure/#:%7E:text=Wastewater%20treatment%20scores%20are%20highest,countries%20treat%20less%20than%205%25">less than 5%</a> of the wastewater they generate. Only a few countries, among them South Africa and neighbouring Botswana, treat <a href="https://inweh.unu.edu/un-500-million-live-in-19-african-nations-deemed-water-insecure/#:%7E:text=Wastewater%20treatment%20scores%20are%20highest,countries%20treat%20less%20than%205%25.">25% to 50%</a> of their wastewater. This means there is more to be learned from these countries.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="African map with indicators of where the research was done" src="https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=441&fit=crop&dpr=1 600w, https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=441&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=441&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=555&fit=crop&dpr=1 754w, https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=555&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/526491/original/file-20230516-17-1q28nu.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=555&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Distribution of African studies on antimicrobial resistance in wastewater between 2012 and 2022. Numbers represent the number of studies identified within the reviewed period. Only counties that reported at least one study in the review period are labelled.</span>
</figcaption>
</figure>
<p>In South Africa, studies on antimicrobial resistance in wastewater were done in only a few of the provinces. Also, not all the studies were done on wastewater treatment plants. This means the source of the resistance could not be traced. In addition, there were differences in the methods used and the results reported.</p>
<p>We found monitoring challenging even where wastewater treatment plants were available because of the lack of technical skills needed for genomic sequencing. Genomic approaches study the DNA of all the microrganisms in the wastewater, instead of focusing on only a few. Furthermore, there are no standardised approaches to these studies. So, it was difficult to compare findings from different locations. </p>
<h2>Recommendations</h2>
<p>The absence of wastewater treatment plants in many African countries means that it will be hard for them to actively implement wastewater-based antimicrobial resistance surveillance. Governments must invest in connecting their populations to sewer networks to address this problem. This is crucial for overall hygiene and health. And it will offer important sources of information for researchers trying to detect resistant microorganisms in communities. </p>
<p>Once sewer networks are in place, standardised protocols for assessing antimicrobial resistance in wastewater treatment plants must be established. The protocols should consider the sampling regime and frequency, the organisms targeted, what antibiotics need to be tested, and what methods should be used.</p>
<p>There is also a need to build capacity in sequencing technologies and bioinformatics. This will ensure that there are enough people with the knowledge required to analyse the large volumes of data generated in these studies. Funding bodies must finance researchers in sub-Saharan countries as sequencing technologies are not yet widespread, and the cost of using these facilities is still high.</p>
<p>People may consider wastewater as something undesirable that just needs to be flushed away. But studying this valuable resource could provide early warning about potential disease outbreaks, especially those involving antimicrobial-resistant microorganisms.</p><img src="https://counter.theconversation.com/content/202050/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Akebe Luther King Abia receives funding from Water Research Commission. Luther King is an Associate Professor of Applied and Environmental Microbiology at the College of Health Sciences, University of KwaZulu-Natal. He is also a Senior Visiting Scientist in the One Health Group at the University of Venda. Luther King is also the Founder and CEO of the Environmental Research Foundation (ERF) and an Aspen New Voices Fellow Alumni.</span></em></p><p class="fine-print"><em><span>Afsatou Ndama Traore works for the University of Venda. She has received funds from the South African Medical Research Council (SAMRC). </span></em></p><p class="fine-print"><em><span>Natasha Potgieter is the Executive Dean for the Faculty of Science, Engineering and Agriculture at the University of Venda and has received funding from Water Research Commission, National Research Council and Department of Health in South Africa.</span></em></p>Wastewater treatment plants receive wastewater from a variety of sources. This makes them useful proxies for determining the burden of antimicrobial resistance in communities.Akebe Luther King Abia, Associate professor, University of KwaZulu-NatalAfsatou Ndama Traore, Associate Professor: Department of Biochemistry & Microbiology, University of VendaNatasha Potgieter, Executive Dean: Faculty of Science, Engineering and Agriculture, University of VendaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2002262023-04-11T12:04:46Z2023-04-11T12:04:46ZLooming behind antibiotic resistance is another bacterial threat – antibiotic tolerance<figure><img src="https://images.theconversation.com/files/519955/original/file-20230407-28-ddggzn.jpg?ixlib=rb-1.1.0&rect=0%2C3%2C2309%2C1292&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tolerant bacteria are dormant until an antibiotic threat has passed, then reemerge to conduct business as usual.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/pseudomonas-aeruginosa-bacterium-illustration-royalty-free-image/1201441647">Christoph Burgstedt/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Have you ever had a nasty infection that just won’t seem to go away? Or a runny nose that keeps coming back? You may have been dealing with a bacterium that is tolerant of, though not yet resistant to, antibiotics. </p>
<p>Antibiotic resistance is a huge problem, contributing to <a href="https://doi.org/10.1016/S0140-6736(21)02724-0">nearly 1.27 million deaths worldwide in 2019</a>. But antibiotic tolerance is a covert threat that researchers have only recently begun to explore. </p>
<p><a href="https://doi.org/10.1371/journal.ppat.1008892">Antibiotic tolerance</a> happens when a bacterium manages to survive for a long time after being exposed to an antibiotic. While <a href="https://doi.org/10.1128/microbiolspec.VMBF-0016-2015">antibiotic-resistant</a> bacteria flourish even in the presence of an antibiotic, tolerant bacteria often exist in a dormant state, neither growing nor dying but putting up with the antibiotic until they can “reawaken” once the stress is gone. Tolerance has been <a href="https://www.doi.org/10.1126/science.aaj2191">linked to the spread of antibiotic resistance</a>.</p>
<p>I am a <a href="https://doerr.wicmb.cornell.edu/current-lab-members/">microbiologist</a> who studies antibiotic tolerance, and I seek to uncover what triggers tolerant bacteria to enter a protective dormant slumber. By understanding why bacteria have the ability to become tolerant, researchers hope to develop ways to avoid the spread of this ability. The exact mechanism that sets tolerance apart from resistance has been unclear. But one possible answer may reside in a process that has been overlooked for decades: how bacteria <a href="https://doi.org/10.3389/fmicb.2020.577564">create their energy</a>.</p>
<h2>Cholera and antibiotic tolerance</h2>
<p>Many antibiotics are designed to <a href="https://doi.org/10.1039/C6MD00585C">break through the bacteria’s outer defenses</a> like a cannonball through a stone fortress. Resistant bacteria are immune to the cannonball because they can either destroy it before it damages their outer wall or change their own walls to be able to withstand the impact. </p>
<p>Tolerant bacteria can remove their wall entirely and avoid damage altogether. No wall, no target for the cannonball to smash. If the threat goes away before too long, the bacterium can rebuild its wall to protect it from other environmental dangers and resume normal functions. However, it is still unknown how bacteria know the antibiotic threat is gone, and what exactly triggers their reawakening. </p>
<p>My colleagues and I at the <a href="https://doerr.wicmb.cornell.edu/">Dörr Lab at Cornell University</a> are trying to understand processes of activation and reawakening in the tolerant bacteria responsible for cholera, <em>Vibrio cholerae</em>. <em>Vibrio</em> is <a href="https://doi.org/10.3389/fitd.2021.691604">rapidly evolving resistance</a> against various types of antibiotics, and doctors are concerned. As of 2010, <em>Vibrio</em> is already <a href="https://doi.org/10.1016/j.vaccine.2019.06.031">resistant to 36 different antibiotics</a>, and this number is expected to continue rising.</p>
<p>To study how <em>Vibrio</em> develops resistance, we chose a strain that is tolerant to a class of antibiotics <a href="https://doi.org/10.3389/fpubh.2016.00231">called beta-lactams</a>. Beta-lactams are the cannonball sent to destroy the bacteria’s fortress, and <em>Vibrio</em> adapts by activating two genes that temporarily remove its cell wall. I witnessed this phenomenon using a microscope. After removing its cell wall, the bacteria activate even more genes that morph it into fragile globs that can survive the effects of the antibiotic. Once the antibiotic is removed or degraded, <em>Vibrio</em> returns to its normal rod shape and continues to grow. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/qCzCj4gQWLk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Normally rod-shaped <em>Vibrio cholerae</em> remove their cell walls and turn into globs in the presence of penicillin, enabling them to survive longer.</span></figcaption>
</figure>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/Zyh6TpwJN0s?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption"><em>Vibrio cholerae</em> revert back to their rod-shaped structure once the antibiotic threat is removed.</span></figcaption>
</figure>
<p>In people, this process of tolerance is seen when a doctor prescribes an antibiotic, typically doxycycline, to a patient infected with cholera. The antibiotic temporarily seems to stop the infection. But then the symptoms start back up again because the antibiotics never fully cleared the bacteria in the first place.</p>
<p>The ability to revert back to normal and grow after the antibiotic is gone is the key to tolerant survival. Exposing <em>Vibrio</em> to an antibiotic for a long enough time would eventually kill it. But a standard course of antibiotics often isn’t long enough to get rid of all the bacteria even in their fragile state.</p>
<p>However, taking a medicine for a prolonged period can harm healthy bacteria and cells, causing further discomfort and illness. Additionally, <a href="https://doi.org/10.3389/fcimb.2020.572912">misuse and extended exposure</a> to antibiotics can increase the chances of other bacteria residing in the body becoming resistant.</p>
<h2>Other bacteria developing tolerance</h2>
<p><em>Vibrio</em> isn’t the only species to exhibit tolerance. In fact, researchers have recently identified many infectious bacteria that have developed tolerance. A bacteria family called <a href="https://doi.org/10.1371/journal.pbio.1001928">Enterobacteriaceae</a>, which include major food-borne disease pathogens <a href="https://doi.org/10.1371/journal.pbio.1001928"><em>Salmonella</em></a>, <a href="https://doi.org/10.1128/AAC.01282-08"><em>Shigella</em></a> and <a href="https://doi.org/10.1038/s41598-021-85509-7"><em>E. coli</em></a>, are just a few of the many types of bacteria that are capable of antibiotic tolerance.</p>
<p>As every bacterium is unique, the way one develops tolerance seems to be as well. Some bacteria, like <em>Vibrio</em>, <a href="https://doi.org/10.1128/AAC.00756-19">erase their cell walls</a>. Others can <a href="https://doi.org/10.1038/nchembio.1754">alter their energy sources, increase their ability to move or simply pump out</a> the antibiotic.</p>
<p>I recently found that a <a href="https://doi.org/10.1128/jb.00476-22">bacterium’s metabolism</a>, or the way it breaks down “food” to make energy, may play a significant role in its ability to become tolerant. Different structures within a bacterium, including its outer wall, are made of specific building blocks like proteins. Stopping the bacterium’s ability to craft these pieces weakens its wall, making it more likely to take damage from the outside environment before it can take the wall down.</p>
<h2>Tolerance and resistance are connected</h2>
<p>Although there has been considerable research on how bacteria develop tolerance, a key piece of the puzzle that has been neglected is how tolerance leads to resistance.</p>
<p>In 2016, researchers discovered how to <a href="https://doi.org/10.1038/nmicrobiol.2016.20">make bacteria tolerant in the laboratory</a>. After repeated exposure to different antibiotics, <em>E. coli</em> cells were able to adapt and survive. DNA, the genetic material containing instructions for cell function, is a fragile molecule. When DNA is damaged rapidly by stress, such as antibiotic exposure, the cell’s repair mechanisms tend to mess up and cause mutations that can create resistance and tolerance. Because <em>E. coli</em> is similar to many different types of bacteria, these researchers’ findings revealed that, ironically, essentially any bacteria can develop tolerance if pushed to their limits by the antibiotics meant to kill them. </p>
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<figcaption><span class="caption">Bacteria form large communities in biofilms.</span></figcaption>
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<p>Another recent key discovery was that the longer bacteria remain tolerant, the more likely they are to <a href="https://doi.org/10.1073/pnas.2209043119">develop mutations leading to resistance</a>. Tolerance allows bacteria to develop a resistance mutation that reduces their chances of being killed during antibiotic treatment. This is especially relevant to bacterial communities often seen in <a href="https://doi.org/10.2147/IDR.S379502">biofilms that tend to coat high-touch surfaces in hospitals</a>. Biofilms are slimy layers of bacteria that ooze a protective jelly that makes antibiotic treatment difficult and DNA sharing between microbes easy. They can induce bacteria to evolve resistance. These conditions are thought to mimic what could be happening during antibiotic-treated infections, in which many bacteria are living next to one another and sharing DNA. </p>
<p>Researchers are calling for more research into antibiotic tolerance with the hope that it will lead to <a href="https://doi.org/10.1128/mBio.02095-19">more robust treatments</a> in both infectious diseases and cancers. And there is reason to be hopeful. In one promising development, a mouse study found that <a href="https://doi.org/10.1126/science.1211037">decreasing tolerance also reduced resistance</a>. </p>
<p>Meanwhile, there are steps everyone can take to aid in the battle against antibiotic tolerance and resistance. You can do this by <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">taking an antibiotic exactly as prescribed</a> by a doctor and finishing the entire bottle. Brief, inconsistent exposure to a medicine primes bacteria to become tolerant and eventually resistant. Smarter use of antibiotics by everyone can stop the evolution of tolerant bacteria.</p><img src="https://counter.theconversation.com/content/200226/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Megan Keller receives funding from the National Science Foundation Graduate Research Fellowship Program and the National Institutes of Health (NSF GRFP #DGE-1650441 and NIH R01-AI143704)</span></em></p>Antibiotic resistance has contributed to millions of deaths worldwide. Research suggests that any bacteria can develop antibiotic tolerance, and possibly resistance, when pushed to their limits.Megan Keller, Ph.D. Candidate in Microbiology, Cornell UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2032052023-04-06T12:07:20Z2023-04-06T12:07:20ZDeadly fungus Candida auris is spreading across US hospitals - a physician answers 5 questions about rising fungal infections<figure><img src="https://images.theconversation.com/files/519667/original/file-20230405-14-l85lwf.jpg?ixlib=rb-1.1.0&rect=215%2C32%2C6186%2C3847&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Candida auris is a fungal yeast that can infect humans.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/candida-yeast-and-hyphae-stages-illustration-royalty-free-illustration/1296293760?phrase=candida%20auris&adppopup=true">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p><em>In late March 2023, the U.S. Centers for Disease Control and Prevention highlighted the <a href="https://www.cdc.gov/media/releases/2023/p0320-cauris.html">threat posed by a rapidly spreading fungus</a> called Candida auris that is causing infections and deaths among hospital patients across the country. The unexpected rise of this recently discovered pathogen is part of a larger trend of increasing fungal infections in the U.S.</em></p>
<p><em><a href="https://directory.hsc.wvu.edu/Individual/Index/31722">Arif R. Sarwari</a> is a physician and professor of infectious diseases at West Virginia University. Amid rising concerns among doctors and public health officials, Sarwari helped explain what Candida auris is, how it is spreading and how worried people in the U.S. should be.</em></p>
<h2>1. What is Candida auris?</h2>
<p><em>Candida auris</em> is a recently identified, single-cell fungus that can infect humans and is moderately <a href="https://www.cdc.gov/fungal/candida-auris/index.html">resistant to existing antifungal drugs</a>. You might be familiar with superficial fungal infections – like athlete’s foot or vaginal yeast infections – which are quite common and don’t pose significant risks to most people. In contrast, <em>Candida auris</em> and other related fungi can <a href="https://doi.org/10.2174/1389450120666190924155631">cause infections within a person’s body</a> and are <a href="https://doi.org/10.3390%2Fjof7010031">much more dangerous</a>.</p>
<p><em>Candida auris</em> is a type of yeast that was first identified in 2009 and is one of a number of species in the candida family that can infect people. In the past, most invasive candida infections were <a href="https://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html">caused by <em>Candida albicans</em></a>. Recently, though, infections with species of candida that are much more resistant to drugs than <em>Candida albicans</em> – <a href="https://www.cdc.gov/media/releases/2023/p0320-cauris.html">like <em>Candida auris</em></a> – have shot up, with a nearly <a href="https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html">fivefold increase since 2019</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A person holding an IV line with a patient's arm." src="https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=501&fit=crop&dpr=1 754w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=501&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/519668/original/file-20230405-22-9491i2.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=501&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Candida fungi can get into a person’s bloodstream through a contaminated IV line and cause a blood infection.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/checking-a-cannula-royalty-free-image/622263704?phrase=IV%20catheter&adppopup=true">Richard Bailey/Corbis Documentary via Getty Images</a></span>
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<h2>2. How dangerous are candida infections?</h2>
<p>For the most part, healthy people do not have to worry about invasive candida infections. There are two groups of people who are <a href="https://doi.org/10.1056/NEJMra1315399">most at risk for dangerous candida infections</a>: first are patients in intensive care units who also have central intravenous catheters and are receiving broad spectrum antibiotics. Patients with weak immune systems, such as cancer patients on chemotherapy or patients with human immunodeficiency virus, are also at high risk of candida infection.</p>
<p>Nearly all people have candida fungi growing in their guts and on their skin as part of their microbiome. When a person is healthy, candida numbers are low, but the fungi can proliferate rapidly and overcome a person’s immune system when a patient is <a href="https://doi.org/10.1016/0195-6701(95)90036-5">sick and on antibiotics</a>. </p>
<p>If candida cells on a person’s skin contaminate an intravenous line, the fungus can get into a patient’s bloodstream and cause often deadly bloodstream infections. Candida species are the fourth most-common cause of <a href="https://doi.org/10.1086/421946">hospital associated bloodstream infections</a>. </p>
<p>There are three classes of antifungal drugs that can be used to <a href="https://doi.org/10.1016/j.idc.2021.03.005">fight invasive candida infections</a>. <em>Candida albicans</em> is susceptible to all three and easier to treat than <em>Candida auris</em>, which is moderately <a href="https://doi.org/10.3947/ic.2022.0008">resistant to all three classes of antifungals</a>.</p>
<h2>3. How common are invasive fungal infections?</h2>
<p>The CDC estimates that in the U.S., around <a href="https://www.cdc.gov/fungal/diseases/candidiasis/invasive/statistics.html">25,000 patients get candida bloodstream infections</a> every year. </p>
<p>Candida bloodstream infections are best understood as a tale of two eras. In the past, they were almost always caused by drug-susceptible <em>Candida albicans</em> that arose endogenously from a patient’s own microbiome. There was no concern about infections spreading to other patients.</p>
<p>The recent emergence of drug-resistant and more transmissible <em>Candida auris</em> is <a href="https://www.cdc.gov/media/releases/2023/p0320-cauris.html">raising alarms</a> among health professionals. Because this species can contaminate surfaces and easily spread from patient to patient, the fungus is causing outbreaks both <a href="https://doi.org/10.1016/j.micpath.2018.09.014">within and between hospitals</a>. </p>
<p><iframe id="H18dQ" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/H18dQ/2/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>4. Why are fungal infections increasing?</h2>
<p>Fungal infections have been rising in the U.S. in recent years, especially infections caused by <em>Candida auris</em>. The pathogen only caused a few infections each year between 2013 and 2016, but starting in 2017, infections began to rise rapidly with <a href="https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html">2,377 confirmed cases recorded in 2022</a> according to the CDC. Deaths caused by all candida infections are rising, too, from 1,010 in 2018 <a href="https://www.cdc.gov/fungal/cdc-and-fungal/burden.html">to nearly 1,800 in 2021</a>.</p>
<p>The reasons for this increase are complicated, but I think there are two main drivers: more, sicker patients in hospitals and a stressed health system, both of which got worse during the COVID-19 pandemic.</p>
<p>Hospitals are seeing more very sick patients with weak immune systems, especially as the population ages. This means there are more susceptible patients at hospitals to begin with. </p>
<p>Additionally, any time the health system is stressed – like during a pandemic – drug-resistant <a href="https://www.cdc.gov/drugresistance/pdf/covid19-impact-report-508.pdf">bacterial and fungal infections increase</a>. This is because very sick patients are usually in crowded wards and exposed to many antibiotics. In addition, loss of hospital staff and increased workload results in lower quality sanitation - causing more spread of resistant pathogens.</p>
<p>I view the rise of drug-resistant fungi like <em>Candida auris</em> through the same lens as <a href="https://theconversation.com/antibiotic-resistance-is-at-a-crisis-point-government-support-for-academia-and-big-pharma-to-find-new-drugs-could-help-defeat-superbugs-169443">worsening antibiotic resistance</a>. The more antibiotics people use, the greater the chances a resistant strain will become dominant.</p>
<h2>5. What can the medical community do about it?</h2>
<p>There are a few options for fighting the rise of drug-resistant <em>Candida auris</em>. </p>
<p>The most effective measures are <a href="https://www.ncbi.nlm.nih.gov/books/NBK563297/">good infection control practices</a>. These behaviors and protocols include practicing good hand hygiene before and after each patient contact, wearing isolation gowns and gloves that are carefully discarded in a patient’s room, and taking measures to detect <em>Candida auris</em> infections early and isolate patients to prevent the spread. Though relatively simple, these actions are key to preventing the spread of all antibiotic-resistant pathogens, not just fungi.</p>
<p>The second option is to develop better drugs to treat new, antifungal-resistant strains of candida. Many new antifungal drugs are <a href="https://doi.org/10.3390%2Fjof8111144">already under development</a>. However, prevention through sound infection control will always remain foundational, as further drug development is akin to an arms race.</p><img src="https://counter.theconversation.com/content/203205/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Arif R. Sarwari does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Candida auris is a relatively new addition to a family of fungi that can infect people. Most of these infections occur in sick, hospitalized patients and can be deadly.Arif R. Sarwari, Professor of Infectious Diseases, West Virginia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1977832023-02-28T13:26:32Z2023-02-28T13:26:32ZOne easy way to fight antibiotic resistance? Good hand hygiene<figure><img src="https://images.theconversation.com/files/512265/original/file-20230224-2018-lwzgz6.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2121%2C1412&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Washing your hands reduces your risk of transmitting and contracting harmful bacteria from other people and the environment.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/female-doctor-uses-hand-santizer-royalty-free-image/1254704741">SDI Productions/E+ via Getty Images</a></span></figcaption></figure><p>Can washing your hands help stop the evolution of antibiotic resistance? Mathematically, <a href="https://doi.org/10.1093/emph/eoac038">it’s possible</a>.</p>
<p><a href="https://medlineplus.gov/antibiotics.html">Antibiotics</a> save lives by killing bacteria that cause infections. But antibiotics don’t just kill infection-causing bacteria or stay in the area of the body where the infection is occurring. Instead, antibiotics spread across the body and inhibit or kill any sensitive bacteria they encounter.</p>
<p>While bacteria that are more sensitive to the antibiotics are killed off, those that are able to survive will continue to reproduce with less competition. This results in increasing abundance of resistant bacteria that can <a href="https://www.cdc.gov/drugresistance/about/how-resistance-happens.html">undermine the effectiveness of the antibiotic</a>. </p>
<p><a href="https://scholar.google.com/citations?user=WcKtVOkAAAAJ&hl=en">I am a researcher</a> who studies the evolution of antibiotic resistance. During my medical training, I was taught about the importance of hospital hygiene practices like <a href="https://www.cdc.gov/drugresistance/protect-yourself-family.html">hand-disinfection</a>. It is well established that good hygiene can help prevent transmission of harmful bacteria from other people or from the environment. I came to wonder how hygiene affects the evolution of antibiotic resistance.</p>
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<a href="https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Nurse washing hands with foamy hand sanitizer from dispenser." src="https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512266/original/file-20230224-1668-g30sai.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Hand-washing is an essential component of hospital hygiene practices.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/using-hand-sanitizer-royalty-free-image/182440832">nano/E+ via Getty Images</a></span>
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<p>So I teamed up with my colleagues <a href="https://portal.research.lu.se/en/persons/magnus-aspenberg">Magnus Aspenberg</a>, <a href="https://portal.research.lu.se/en/persons/sara-maad-sasane">Sara Maad Sasane</a>, <a href="https://scholar.google.se/citations?user=M2HsaIsAAAAJ&hl=sv">Fredrik Nilsson</a> and <a href="https://scholar.google.com/citations?user=ZgN-OgMAAAAJ&hl=en">Sam Brown</a>, experts in mathematics, statistics and microbial evolution, to answer this question. </p>
<p>We built a <a href="https://doi.org/10.1093/emph/eoac038">mathematical model of antibiotic resistance evolution</a>. In this model, resistant and sensitive bacteria compete in the microbial communities living in patients and transmit from one patient to another. We studied the effects of two parameters: hygiene (or use of an alcohol-based hand rub), which limits how much bacteria spreads between patients, and antibiotic use, which selects for resistant bacteria by killing sensitive ones.</p>
<p>We found that hygiene and antibiotic use interact. Antibiotic use had less of an effect on the evolution of antibacterial resistance as hygiene levels increased. This is because evolution toward resistance depends on variation in bacterial sensitivity to antibiotics. By affecting the distribution of resistant and sensitive bacterial strains across patients, hygiene limits the bacterial diversity needed to evolve resistance.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/ZvhFeGEDFC8?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The effectiveness of antibiotics is under threat from bacteria rapidly evolving resistance against them.</span></figcaption>
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<p>Research on the evolution of antimicrobial resistance has focused more on evolutionary selection than hygiene. Most studies investigate, for example, whether a <a href="https://doi.org/10.1371/journal.pcbi.1004689">high or a low dose of a drug</a> is better to prevent resistance. Incorporating hygiene and other interventions into research on antibiotic resistance could help build a more comprehensive understanding of how bacteria evolve to become resistant.</p>
<p>The <a href="https://www.cdc.gov/drugresistance/protect-yourself-family.html">role of good hygiene</a> in preventing illness is already well accepted in practice. Our findings underscore its importance by highlighting the role it plays in the evolutionary process of bacterial resistance.</p><img src="https://counter.theconversation.com/content/197783/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The work was supported by grants from the Wenner-Gren Foundations, the Royal Physiographic Society of Lund (the Fund of the Hedda and John Forssman Foundation), the Sten K Johnsson Foundation, the Crafoord Foundation, the Cystic Fibrosis Foundation, and the Centers for Disease Control and Prevention (BAA 2017-OADS-01).</span></em></p>Using a mathematical model, researchers found that good hygiene can reduce the harmful effects of antibiotic use.Kristofer Wollein Waldetoft, Postdoctoral Fellow in Infection Medicine, Georgia Institute of TechnologyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1994802023-02-15T15:51:33Z2023-02-15T15:51:33ZAntibiotics are being inappropriately prescribed for COVID, increasing the threat of antimicrobial resistance – research<figure><img src="https://images.theconversation.com/files/510283/original/file-20230215-4579-ie0u3v.jpg?ixlib=rb-1.1.0&rect=25%2C0%2C2800%2C1861&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotics are for bacterial infections – they shouldn't be prescribed to treat viruses.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmasict-serving-customer-drug-store-1857327172">PH888/Shutterstock</a></span></figcaption></figure><p>Antibiotics are drugs designed to treat infections caused by bacteria (for example, skin infections). They don’t work on infections caused by other microbes such as viruses (including COVID and flu) or fungi (for example, thrush).</p>
<p>Beyond treating bacterial infections, antibiotics also have other important uses, like preventing infection <a href="https://www.ecdc.europa.eu/en/publications-data/directory-guidance-prevention-and-control/prudent-use-antibiotics/peri-operative">during major surgery</a>.</p>
<p>Bacteria have existed for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413235/">billions of years</a> and are adept at survival. Since the early 20th century when antibiotics <a href="https://www.sciencedirect.com/science/article/pii/S1369527419300190">were introduced</a> as medicines to fight infections, bacteria have worked out several ways to protect themselves and avoid being killed. </p>
<p>When antibiotics are misused or overused, more opportunities arise for bacteria to develop and improve these protective tools. This contributes to a problem called antibiotic or <a href="https://theconversation.com/antimicrobial-resistance-now-causes-more-deaths-than-hiv-aids-and-malaria-worldwide-new-study-175351">antimicrobial resistance</a>, where bacteria evolve over time so that antibiotics no longer work against them. This makes infections more difficult to treat as doctors have fewer antibiotics to choose from, in turn <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext">increasing the risk</a> of serious illness and death. </p>
<p>But how has the COVID pandemic affected antibiotic use, and the problem of antibiotic resistance? A <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00025-1/fulltext">recent study</a> which analysed pharmaceutical sales data from 71 countries suggests that as COVID cases went up, so did antibiotics sales.</p>
<p>The researchers examined <a href="https://www.iqvia.com/solutions/commercialization/brand-strategy-and-management/market-measurement/midas">sales</a> of four antibiotic families commonly prescribed in respiratory infections (cephalosporins, penicillins, macrolides and tetracyclines) from March 2020 to May 2022.</p>
<p>They sourced monthly sales data for these antibiotics per 1,000 people, and from a <a href="https://ourworldindata.org/coronavirus">separate database</a> also gathered data on COVID infections. For comparison, the researchers used global antibiotic sales trends from 2018.</p>
<p>Not surprisingly, they found antibiotics sales fell sharply over April and May 2020. This drop was likely a result of fewer infections spreading while people were under strict lockdown measures, and perhaps some people <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8834942/">avoiding healthcare</a>. </p>
<p>However, antibiotic sales gradually increased thereafter. The resurgence of non-COVID respiratory viral infections <a href="https://theconversation.com/qanda-is-the-common-cold-really-much-worse-this-year-170338">with the easing of lockdowns</a> may have contributed to increased antibiotics sales from 2021 onward. By May 2022, sales had returned to just below pre-pandemic levels. </p>
<p>Using statistical models, the researchers found an association between increasing COVID rates and higher antibiotic sales. </p>
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Read more:
<a href="https://theconversation.com/covid-is-caused-by-a-virus-so-why-are-researchers-treating-it-with-antibiotics-171897">COVID is caused by a virus – so why are researchers treating it with antibiotics?</a>
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<h2>COVID and antibiotics</h2>
<p>Research has <a href="https://pubmed.ncbi.nlm.nih.gov/35263322/">previously identified</a> <a href="https://pubmed.ncbi.nlm.nih.gov/35237702/">seasonal spikes</a> in <a href="https://pubmed.ncbi.nlm.nih.gov/22752512/">antibiotic use</a> correlating with the winter virus season. This is concerning because antibiotics are designed to target bacteria, and <a href="https://theconversation.com/why-you-shouldnt-take-antibiotics-for-colds-and-flu-105520">have no effect on viruses</a> such as those which cause colds or flu.</p>
<p>Many antibiotic prescriptions in these cases <a href="https://www.bmj.com/content/364/bmj.k5092">are inappropriate</a>. However, distinguishing viral from bacterial infection can be difficult clinically, especially in the initial stages of infection. This may explain why patients are sometimes started on antibiotics while waiting for laboratory test results.</p>
<p>In certain situations, antibiotics are appropriate. For example, viral lung infections can damage airways and compromise the normal <a href="https://pubmed.ncbi.nlm.nih.gov/32712106/">protective immune responses</a>. This can allow bacteria to attach to airway cells and invade, causing a secondary bacterial infection. </p>
<p>Early in the COVID pandemic, antibiotic prescribing was probably based on previous experience with flu, where rates of secondary bacterial infection had been reported to be <a href="https://pubmed.ncbi.nlm.nih.gov/27232677/">as high as 65%</a>. But as the pandemic progressed, data indicated bacterial co-infection in COVID was <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00025-1/fulltext">less than 10%</a>. Specific antibiotic prescribing guidelines for patients with COVID <a href="https://pubmed.ncbi.nlm.nih.gov/33010444/">were published</a>.</p>
<p>Yet despite increasing evidence that bacterial co-infection in COVID <a href="https://pubmed.ncbi.nlm.nih.gov/32820807/">is low</a>, research has shown antibiotic prescribing among COVID patients has <a href="https://pubmed.ncbi.nlm.nih.gov/35913964/">remained high</a>. This latest study provides further evidence that antibiotics are commonly prescribed to COVID patients. </p>
<figure class="align-center ">
<img alt="A young male pharmacist makes notes on a clipboard." src="https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/510284/original/file-20230215-3672-hnng62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">The study analysed pharmaceutical sales data from 71 countries.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/young-african-american-man-pharmacist-standing-1456452941">SofikoS/Shutterstock</a></span>
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<h2>Some limitations</h2>
<p>Similar to other large studies on antibiotic consumption, this study uses antibiotic sales data as a proxy for antibiotic use. This sales data is already captured in databases from a number of countries, and is more readily accessible than data on antibiotic prescriptions in many countries, which may not be captured electronically. But because of the nature of the data, we can’t draw any conclusions as to how many of the antibiotics purchased were appropriately prescribed.</p>
<p>Further, data on non-COVID infections, which can impact antibiotic prescribing and rates of resistance, was not included. The pausing of routine childhood vaccination programmes <a href="https://www.sciencedirect.com/science/article/pii/S2214109X2100512X">during the pandemic</a> probably increased bacterial infection risk in some countries, necessitating increased antibiotic prescriptions. This may have contributed to the trends seen. </p>
<p>When interpreting these findings, it’s also important to note that not all continents were represented equally. Some large countries such as Bangladesh were excluded. </p>
<p>Finally, testing protocols vary between countries, so there may have been some inconsistencies in the COVID case data. And access to antibiotics <a href="https://pubmed.ncbi.nlm.nih.gov/26603919/">is inconsistent globally</a>, especially in low- and middle-income countries, which likely impacted some countries’ sales rates. </p>
<h2>The challenge of antibiotic resistance</h2>
<p>Antibiotic resistance is a <a href="https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00502-2/fulltext">global threat to public health</a>, impacting humans, animals and the environment.</p>
<p>Inappropriate antibiotic prescribing in COVID could be contributing to the problem. To address this, we need to see more alignment in guidelines and protocols for clinicians, especially linking diagnosis of viral respiratory infections with antibiotic prescribing guidelines. Support for the development of <a href="https://pubmed.ncbi.nlm.nih.gov/31229593/">rapid diagnostics</a> to confirm or rule out <a href="https://www.nature.com/articles/s41598-021-03741-7">co-infection</a> would also give clinicians confidence to avoid antibiotics in some patients. </p>
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Read more:
<a href="https://theconversation.com/coronavirus-pandemic-is-paving-the-way-for-an-increase-in-superbugs-135389">Coronavirus pandemic is paving the way for an increase in superbugs</a>
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<p>More broadly, tackling the issue of <a href="https://fems-microbiology.org/one-health-10-ways-to-tackle-antibiotic-resistance/">antibiotic resistance</a> requires increased public awareness of the issue, enhanced global surveillance of antibiotic use and resistance, improved infection control policies, and better sanitation. </p>
<p>This rests on <a href="https://www.frontiersin.org/articles/10.3389/fcimb.2021.771510/full">a coordinated</a> “<a href="https://www.ecdc.europa.eu/en/publications-data/antimicrobial-resistance-eueea-one-health-response">One Health</a>” approach – <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047147/">a joint global effort</a> across a range of sectors to provide solutions for human, animal and environmental health. This strategy should address health inequalities and will require bespoke interventions, especially in lower- and middle-income countries.</p><img src="https://counter.theconversation.com/content/199480/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Deirdre Fitzgerald Hughes receives funding from Science Foundation Ireland and the Irish Research Council.</span></em></p><p class="fine-print"><em><span>Fidelma Fitzpatrick does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Antibiotics are a cornerstone of modern medicine, but resistance is a big challenge – and it’s possibly being exacerbated by the COVID pandemic.Fidelma Fitzpatrick, Consultant Microbiologist, Beaumont Hospital, Dublin, Ireland and Professor and Head of Department, Clinical Microbiology, RCSI University of Medicine and Health SciencesDeirdre Fitzgerald Hughes, Senior Lecturer, Clinical Microbiology, RCSI University of Medicine and Health SciencesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1987092023-02-09T18:58:21Z2023-02-09T18:58:21ZThe fight against antibiotic resistance is growing more urgent, but artificial intelligence can help<figure><img src="https://images.theconversation.com/files/506943/original/file-20230129-39252-82ujl8.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C3840%2C2160&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Artificial intelligence can be used to develop new drugs, quickly and cheaply.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Since the discovery of penicillin in the late 1920s, antibiotics have “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/">revolutionized medicine and saved millions of lives</a>.” Unfortunately, the effectiveness of antibiotics is now threatened by <a href="https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance">the increase of antibiotic-resistant bacteria globally</a>.</p>
<p>Antibiotic-resistant infections cause the deaths of up to <a href="https://www.ox.ac.uk/news/2022-01-20-estimated-12-million-people-died-2019-antibiotic-resistant-bacterial-infections">1.2 million people annually</a>, making them one of the leading causes of death. </p>
<p>There are several factors contributing to this crisis of resistance to antibiotics. These <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/">include overusing and misusing antibiotics in treatments</a>. In addition, pharmaceutical companies are <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/">over-regulated and disincentivized from developing new drugs</a>.</p>
<p>The World Health Organization estimates that <a href="https://www.who.int/news/item/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis">10 million people will die from such infections by the year 2050</a>. </p>
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Read more:
<a href="https://theconversation.com/jeff-beck-dies-of-bacterial-meningitis-what-you-need-to-know-about-the-disease-197721">Jeff Beck dies of bacterial meningitis – what you need to know about the disease</a>
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<p>The impacts of antibiotic-resistant infections are wide-ranging. In the absence of effective prevention and treatment for bacterial infections, medical procedures such as organ transplants, chemotherapy and caesarean sections become far riskier. That’s <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">because the severity of bacteria-related infections is increasing</a> and untreated infections can cause a variety of health problems.</p>
<h2>Discovering new antibiotics</h2>
<p>Antibiotics treat illnesses by attacking the bacteria that cause them <a href="https://www.medicalnewstoday.com/articles/10278#what-are-they">by destroying them or preventing them from reproducing</a>. </p>
<p>The discovery of new antibiotics has the potential to save millions of lives. The last discovery of a <a href="https://www.pewtrusts.org/en/research-and-analysis/articles/2021/02/18/researcher-explains-challenges-in-finding-novel-antibiotics">novel class of antibiotics was in 1984</a>. But it’s not easy to find a truly new antibiotic: <a href="https://wellcome.org/news/why-is-it-so-hard-develop-new-antibiotics">only one out of every 15 antibiotics that enter pre-clinical development reach patients</a>.</p>
<p>Developing a new drug is a costly, and often lengthy process. Also, the process of bringing novel drugs to the market and making them accessible presents formidable challenges.</p>
<p>This is where artificial intelligence (AI) comes into play, because it allows researchers to quickly and accurately design and assess potential drugs.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="a shelf of packaged medications, the hands of someone wearing a white coat and holding a pill packet are visible" src="https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/509234/original/file-20230209-28-dfh4qg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=474&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Getting a new drug from development to market is a costly, and often lengthy process.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
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</figure>
<h2>The role of AI in drug design</h2>
<p>There has been an explosion in research in recent years in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626864/">the use of AI for drug design and discovery</a>. AI can identify new antibiotics that are structurally distinct from currently available ones and effective against a range of bacteria. </p>
<p>In order to discover more effective antibiotics, we need to understand the structural basis of resistance, and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944398/">this understanding enables rational design principles</a>. Developing effective second-generation antibiotics often involves optimizing first-generation drugs.</p>
<p>In drug development, a significant amount of money is spent developing and evaluating each generation of compounds. Researchers can use AI tools to teach computers themselves to find quick and cheap ways of discovering such novel medications.</p>
<p>Artificial intelligence is already showing promising results in <a href="https://news.mit.edu/2020/artificial-intelligence-identifies-new-antibiotic-0220">finding new antibiotics</a>. In 2019, researchers used a deep learning approach to identify the wide-spectrum antibiotic Halicin. Halicin had previously <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667321/">failed clinical trials as a treatment for diabetes</a>, but AI suggested a different application.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1462797432937492483"}"></div></p>
<p>Given the early identification of such a potentially strong antibiotic using artificial intelligence, a large number of such broad-spectrum antibiotics that could be effective against a range of bacteria might be identified. These drugs still need to undergo clinical trials.</p>
<p>Researchers at the U.S. National Institutes of Health harnessed AI’s predictive power to demonstrate <a href="https://www.embopress.org/doi/full/10.15252/msb.202211081">AI’s potential to accelerate the process of selecting future antibiotics</a>.</p>
<p>AI can be trained to screen and discover new drugs much faster — <a href="https://mansbach-lab.github.io/research/">our lab at Concordia University</a> is using this approach to identify antibiotics that would target bacterial RNA. </p>
<h2>Algorithmic learning</h2>
<p>Researchers design an algorithm that uses data from databases <a href="https://zinc.docking.org/">like ZINC</a> (a collection of commercially available chemicals that can be used for virtual screening) to figure out how molecules and their properties relate. The AI models extract information from the database to analyze their patterns. </p>
<p>The models created by the algorithm are <a href="https://directorsblog.nih.gov/2022/09/13/using-ai-to-find-new-antibiotics-still-a-work-in-progress/">trained on pre-existing data</a>. AI can rapidly sift through huge amounts of data to understand important patterns in the content or structure of a molecule. </p>
<p>We have seen the potential of current models to <a href="https://aimagazine.com/articles/deepminds-alphafold-joins-ai-search-for-new-antibiotics">correctly predict how bacterial proteins and anti-bacterial agents would interact</a>. But in order to maximize AI’s predictive capabilities, further refinement will still be required. </p>
<h2>Limitations of AI</h2>
<p>Researchers <a href="https://www.brookings.edu/research/how-artificial-intelligence-is-transforming-the-world/">haven’t yet explored the full potential of AI models</a>. With further developments, like increased computing power, AI can become an important tool in science. The development of AI in drug discovery research, as well as finding new antibiotics to treat bacterial infections is a work in progress. </p>
<p>The ability of <a href="https://directorsblog.nih.gov/2022/09/13/using-ai-to-find-new-antibiotics-still-a-work-in-progress/">artificial intelligence to predict and accurately identify</a> leads has shown promising results. </p>
<p>Even when powered by powerful AI approaches, finding new drugs will not be easy. We need to understand that AI is a tool that contributes to research by identifying or predicting an outcome of a research question. </p>
<p>AI is implemented in a number of industries today, and is already changing the world. But it’s not a replacement for a scientist or doctor. AI can help the researcher to enhance or fast-track the process of drug discovery.</p>
<p>Even though we still have a way to go before we can fully utilize this method, there is no doubt that AI will significantly change how drugs are discovered and developed.</p><img src="https://counter.theconversation.com/content/198709/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Vrinda’s doctoral research is funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Research Chairs and Concordia University. She currently works with Molecular Forecaster and has received Mitacs Accelerate Fellowship for her internship project. </span></em></p><p class="fine-print"><em><span>Rachael (Ré) A Mansbach receives funding from NSERC through Discovery Grant #RGPIN-2021-03470 and a Tier II Canada Research Chair in Computational Biophysics. They also work with Molecular Forecaster through a funded Mitacs grant.</span></em></p>Bacterial infections are a growing global challenge. This is due to antibiotic-resistant bacteria, and researchers are turning to AI to develop new drugs.Vrinda Nair, Doctoral Student in Physics, Concordia UniversityRachael (Ré) A Mansbach, Assistant professor, Physics, Concordia UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1965402022-12-16T16:18:51Z2022-12-16T16:18:51ZAntibiotics shortages: what’s causing them and how countries can minimise the impact<figure><img src="https://images.theconversation.com/files/501500/original/file-20221216-19-9xjslg.jpg?ixlib=rb-1.1.0&rect=63%2C0%2C7097%2C4459&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/pharmacist-holding-medicine-box-capsule-pack-704036482">i viewfinder/Shutterstock</a></span></figcaption></figure><p>A variety of antibiotics are currently in short supply <a href="https://www.wsj.com/articles/europe-is-hit-by-shortages-of-antibiotics-11670639357">across Europe</a>. In <a href="https://www.ft.com/content/10688692-57c5-4c84-a333-789df699be6e">the UK</a>, for example, the availability of amoxicillin and penicillin, which are used to treat infections such as strep A, is low.</p>
<p>Medicine shortages are a significant problem around the world, affecting patient welfare and costs of care. A 2021 survey of community pharmacists <a href="https://www.pgeu.eu/publications/press-release-pgeu-medicine-shortages-survey-2021-results/">in 27 European countries</a> confirmed that shortages are a persisting issue. </p>
<p>The current shortage of antibiotics could have negative effects on patients and raises public health concerns. So what’s causing these shortages, and what can we do to ensure people who need antibiotics can access the right ones?</p>
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Read more:
<a href="https://theconversation.com/strep-a-three-doctors-explain-what-you-need-to-look-out-for-195972">Strep A: three doctors explain what you need to look out for</a>
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<p>Our <a href="https://www.bi.edu/research/centres-groups-and-other-initiatives/mia/">research on medicine shortages</a> suggests that antibiotics supply problems are, in many respects, no different from other recent instances of <a href="https://www.bmj.com/content/377/bmj.o1183">drug shortages</a>. They are the result of well-known demand and supply issues.</p>
<p>On the demand side, <a href="https://www.ft.com/content/10688692-57c5-4c84-a333-789df699be6e">changing infection patterns</a> and possibly also the continuing cold snap have contributed to higher than usual use of antibiotics. </p>
<p>In the UK, for example, medical experts have explained that cases of scarlet fever and strep A usually increase <a href="https://ukhsa-newsroom.prgloo.com/news/ukhsa-update-on-scarlet-fever-and-invasive-group-a-strep-3">in the new year</a>. But altered immunity levels in the population related to the COVID pandemic seem to have influenced infection cycles. </p>
<p>The earlier than usual spike in illness was largely unexpected, invalidating demand forecasts and disrupting manufacturers’ production plans. Accordingly, pharmacies have reported difficulties <a href="https://www.theguardian.com/society/2022/dec/09/parents-report-struggle-to-find-antibiotics-uk-strep-a-cases-rise">securing supplies</a> of key antibiotics to meet the spike in demand.</p>
<p>In addition, changing prescription patterns can contribute to demand spikes. A <a href="https://www.theguardian.com/society/2022/dec/06/children-risk-strep-a-england-preventive-antibiotics">recent change of advice</a> in England permitted the use of antibiotics for children at risk of strep A as a “blanket measure”, which in turn likely increased demand for penicillin and amoxicillin. </p>
<p>On the supply side, over-reliance on a small number of suppliers for active pharmaceutical ingredients and other raw materials has made it difficult for manufacturers to match current demand. A specific challenge has been <a href="https://www.wsj.com/articles/europe-is-hit-by-shortages-of-antibiotics-11670639357">China’s zero COVID policy</a> and the constraints this has placed on manufacturing output and logistics.</p>
<p>More broadly, heavy dependence on certain countries as key sources for ingredients and raw materials is a significant issue. China and India together accounted for <a href="https://asia.nikkei.com/static/vdata/infographics/chinavaccine-3/">more than 60%</a> of the supply of active pharmaceutical ingredients globally in 2020. This level of supply market concentration can lead to severe availability issues when medicine supply chains are disrupted.</p>
<p>Another key issue is that many antibiotics, especially those that are not protected by patents (widely known as “generics”), are very cheap. Although low prices make these antibiotics affordable, they also reduce the financial attractiveness for manufacturers, who may decide to discontinue production when supplying these products no longer makes economic sense.</p>
<p>Rising energy costs <a href="https://www.wsj.com/articles/europe-is-hit-by-shortages-of-antibiotics-11670639357">exacerbate these challenges</a> because they increase production costs, which has contributed to some antibiotics manufacturers ceasing production.</p>
<h2>Problems for patients</h2>
<p>If people can’t access the antibiotics they need, this will lead to more cases of severe illness. In very serious cases, it could be life-threatening.</p>
<p>The majority of amoxicillin- and penicillin-based products are “narrow-spectrum” antibiotics, meaning that they target a specific set of infections. Shortages of these products could increase the use of “broad-spectrum” antibiotics, which are meant to treat a host of bacterial infections.</p>
<p>Although this is better than leaving infections untreated, <a href="https://www.reactgroup.org/toolbox/understand/antibiotics/how-do-antibiotics-work/">broad-spectrum antibiotics</a> elevate the risk of antimicrobial resistance, making it more challenging to treat infections in the long run.</p>
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<img alt="A man feels his daughter's forehead, holding a thermometer." src="https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/501501/original/file-20221216-22-w5sujv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">There’s been a big increase in the number of children with Strep A in the UK recently.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sick-little-girl-covered-blanket-lying-561769342">George Rudy/Shutterstock</a></span>
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<h2>What can be done?</h2>
<p>Given the public health risks involved, it’s imperative that antibiotics go to patients who need them today, instead of being held for patients who might need them tomorrow.</p>
<p>An immediate action for governments to take is to actively discourage hoarding by individuals and healthcare professionals to ease demand pressures. The <a href="https://www.pulsetoday.co.uk/news/clinical-areas/paediatrics/government-attempts-to-ease-antibiotics-shortage-with-hoarding-ban/">UK government</a> has already taken steps in this direction. On the pharmacy side, rather than build emergency stocks, pharmacies could exchange information about their stock levels and collaborate to share stock as and when needed.</p>
<p>Governments reimbursing pharmacies for costs associated with <a href="https://amp-theguardian-com.cdn.ampproject.org/c/s/amp.theguardian.com/society/2022/dec/13/uk-pharmacists-report-sharp-rise-in-prices-for-strep-a-antibiotics?utm_source=upday&utm_medium=referral">antibiotics price increases</a>, to ensure they maintain a healthy profit margin, can contribute to supply continuity. Medical experts could also review prescription guidelines so that use of antibiotics is encouraged only in cases where serious health consequences are expected. This would help to manage demand more effectively. </p>
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Read more:
<a href="https://theconversation.com/heres-why-so-many-medications-are-out-of-stock-and-what-to-do-if-it-affects-you-190476">Here’s why so many medications are out of stock — and what to do if it affects you</a>
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<p>Governments also need to work with manufacturers and wholesalers to review their stockpiling policies. Investing in suitably-sized buffer stocks of antibiotics to account for seasonal spikes in demand can help suppliers and healthcare professionals buy time when imbalances between supply and demand occur. Any cost increases associated with supply chain actors holding safety stocks could be covered either through direct government payments or product price increases. </p>
<p>Ultimately, though, fixing medicine shortages requires rethinking procurement systems to incentivise supply security and reducing dependence on remote suppliers of active ingredients and raw materials. The latter might, for instance, involve joint investment in regional manufacturing hubs in Europe.</p><img src="https://counter.theconversation.com/content/196540/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kostas Selviaridis has received funding from the Research Council of Norway for the research project "Measures for Improving Availability of medicines and vaccines" (MIA). </span></em></p><p class="fine-print"><em><span>Nonhlanhla Dube has received funding from the Research Council of Norway for research on "Measures for Improved Availability of medicines and vaccines" (MIA). </span></em></p>These shortages are a result of rising demand and supply chain bottlenecks. But there are things that can be done to reduce harms to public health.Kostas Selviaridis, Senior Lecturer in Operations Management, Department of Management Science, Lancaster UniversityNonhlanhla Dube, Lecturer in Operations Management, Lancaster UniversityLicensed as Creative Commons – attribution, no derivatives.