tag:theconversation.com,2011:/fr/topics/superbug-7060/articles
Superbug – The Conversation
2024-01-05T14:54:09Z
tag:theconversation.com,2011:article/220564
2024-01-05T14:54:09Z
2024-01-05T14:54:09Z
New 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">
<figcaption>
<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>
</figcaption>
</figure>
<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 University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/218879
2023-12-11T22:10:48Z
2023-12-11T22:10:48Z
Antimicrobial 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>
<figcaption>
<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>
</figcaption>
</figure>
<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 University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/177743
2022-03-01T15:51:58Z
2022-03-01T15:51:58Z
Why Canada hasn’t been getting the new antibiotics we need to fight drug-resistant ‘superbugs’
<figure><img src="https://images.theconversation.com/files/448666/original/file-20220226-32700-17obcv1.jpg?ixlib=rb-1.1.0&rect=556%2C1455%2C4760%2C2505&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Canadian doctors don't have easy access to newer antibiotics, and must prescribe older, generic treatments that are increasingly ineffective due to resistance.
</span> <span class="attribution"><span class="source">(Pexels/Shvets Production)</span></span></figcaption></figure><iframe style="width: 100%; height: 175px; border: none; position: relative; z-index: 1;" allowtransparency="" src="https://narrations.ad-auris.com/widget/the-conversation-canada/why-canada-hasn-t-been-getting-the-new-antibiotics-we-need-to-fight-drug-resistant--superbugs-" width="100%" height="400"></iframe>
<p>More than <a href="https://cca-reports.ca/reports/the-potential-socio-economic-impacts-of-antimicrobial-resistance-in-canada/">one-quarter of infections</a> in Canada fail to clear up when people are treated with standard antibiotics. This failure occurs because of a phenomenon called antimicrobial resistance (also called AMR), where bacteria and other microbes develop the ability to resist the effects of drugs designed to kill them. </p>
<figure class="align-right ">
<img alt="A column of yellow spheres above a larger blue blob." src="https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=628&fit=crop&dpr=1 600w, https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=628&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=628&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=790&fit=crop&dpr=1 754w, https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=790&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/448644/original/file-20220225-31520-1xwov44.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=790&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Methicillin-resistant Staphylococcus aureus, a drug-resistant strain of bacteria that is a frequent cause of infections.</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>These drug-resistant microbes — colloquially known as “superbugs” — are becoming increasingly common. In 2019, the World Health Organization (WHO) declared that <a href="https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019">antimicrobial resistance is among the top 10 threats</a> to global health. And while drug resistance has long been forecasted to worsen over time, further research indicates that <a href="https://doi.org/10.1016/S0140-6736(20)32063-8">the problem has accelerated</a> during the COVID-19 pandemic. </p>
<p>As a microbiologist studying how to mitigate antimicrobial resistance, this keeps me up at night.</p>
<p>Thankfully, there are ways to curtail the spread of resistance. For example, ensuring the judicious and appropriate use of antimicrobial medications, like antibiotics, can go a long way — <a href="https://www.cdc.gov/antibiotic-use/core-elements/index.html">a principle called stewardship</a>. One of the best ways to improve stewardship is to ensure that our health-care providers have access to the most current array of treatment options. </p>
<p>Unfortunately, many Canadian physicians do not have easy access to newer antibiotics, and must resort to prescribing older, generic treatments that are increasingly ineffective due to resistance. This prescribing behaviour can lead to even higher resistance rates in the long run, and can prolong infections in sick patients, with poorer health outcomes and higher costs to our health-care system. </p>
<h2>Canada lags behind its international counterparts</h2>
<p>While antimicrobial resistance is a global problem, it may soon become particularly dire in Canada. Today, several novel antibiotics — drugs that microbes have not yet learned to evade — have been approved for use in other jurisdictions but remain unavailable to Canadian patients.</p>
<p><a href="https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab612/6319400?login=true">New research</a> revealed that of 18 novel antibiotics approved and commercially launched in 14 high-income countries over the past 10 years, only two have been introduced in Canada — the fewest of any country on the list. For comparison, the same study showed that the United States brought 17 new antibiotics to market during the same period, while the United Kingdom and Sweden trailed not far behind with 11 and 10, respectively.</p>
<p>So why is Canada lagging so far behind its peers? Well, with colleagues at McMaster University and the <a href="https://amrinnovation.ca/">Canadian Antimicrobial Innovation Coalition</a>, we spent the past year trying to figure that out. </p>
<figure class="align-center ">
<img alt="Hands holding a pharmacist's tray filled with yellow pills" src="https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/448667/original/file-20220226-31836-nxwbaf.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">
<figcaption>
<span class="caption">More than one-quarter of infections in Canada fail to resolve when people are treated with first-line antibiotics.</span>
<span class="attribution"><span class="source">(Pexels/Amornthep Srina)</span></span>
</figcaption>
</figure>
<p>We learned that due to the cost of developing these drugs and their susceptibility to eventual resistance, many <a href="https://doi.org/10.1038/d41586-020-02884-3">pharmaceutical companies have abandoned antibiotic development</a>. </p>
<p>Meanwhile, stewardship principles ensure that newer antibiotics are used only as a last resort, reducing the volume of sales and return on investment for companies that are still willing to bear the costs of development.</p>
<p>On top of that, manufacturers still producing antibiotics tend to shy away from the Canadian market due to Canada’s small population, financial barriers in our publicly funded system and burdensome regulatory processes.</p>
<h2>Potential solutions for a growing problem</h2>
<p>We worked collaboratively with Canadian and global experts from microbiology, industry, economics, policy and medicine to develop potential solutions. <a href="https://iidr.mcmaster.ca/maac/">This work culminated in 30 key recommendations</a>, which were formally submitted to Health Canada and the Public Health Agency of Canada at the end of 2021. Among them, we proposed that the Canadian government:</p>
<ul>
<li>Expedite and streamline the approval of select antibiotics that have already been approved by the European Medicines Agency or the U.S. Food and Drug Administration.</li>
<li>Create specific funding sources to help Canadian hospitals purchase new antibiotics and associated diagnostics.</li>
<li>Establish national forecasts for antibiotics required by Canadian patients, including for drugs not yet approved here.</li>
</ul>
<p>We also called upon government to encourage pharmaceutical companies to bring their products to the Canadian market through an incentive model that is based on an antibiotic’s true value to the Canadian health-care system, rather than on how many doses can be sold. </p>
<p>Several <a href="https://doi.org/10.1016/j.healthpol.2020.11.015">other countries</a> are trying similar strategies to improve access. In 2020, Sweden began guaranteeing minimum revenue to manufacturers in exchange for a guaranteed volume of antibiotics. In the same year, the U.K. began paying manufacturers an annual fee, completely de-linked from sales volume. In 2017, Germany began allowing new antibiotics to bypass its price reference process. And that’s just the short list. </p>
<h2>Lessons from the COVID-19 pandemic</h2>
<figure class="align-right ">
<img alt="Model of a coronavirus with red spikes" src="https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/448668/original/file-20220226-42065-ulkf6s.png?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">The early days of COVID-19 may have given us a glimpse of a future with antimicrobial resistance: An infectious disease with no treatment.</span>
<span class="attribution"><span class="source">(Pixabay)</span></span>
</figcaption>
</figure>
<p>The early days of the pandemic provided a preview of what uncontrolled drug resistance might look like — an infectious disease with no viable treatment options. However, it also showed how federal and provincial governments can co-ordinate to address a serious public health threat.</p>
<p>In the same manner that our policy-makers collaborated to get vaccines into the arms of Canadians, we are imploring them to find ways get novel antibiotics into our pharmacies.</p>
<p>While antimicrobial resistance is a slower-moving pandemic than COVID-19, <a href="https://doi.org/10.1126/science.aaa2868">it will have massive impact</a> on complex medical procedures that we now take for granted, such as joint replacements, cancer chemotherapy or caring for premature babies. More urgency is needed in our efforts to bring new antibiotic options to Canada to slow the development of resistance, to save lives, and to reduce pressure on our health-care system.</p><img src="https://counter.theconversation.com/content/177743/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Funding for development of the McMaster Antibiotic Access and Capacity proposal mentioned in this article was provided in part through unrestricted grants from Merck Canada; Innovative Medicines Canada; the Canadian Antimicrobial Innovation Coalition; and McMaster's Global Nexus for Pandemic Preparedness and Biological Threats. Lori L. Burrows also holds research funding from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Canadian Glycomics Network (Glyconet), and the Ontario Research Fund.</span></em></p>
Canada lags behind other developed countries in access to newer antimicrobials. Here’s why that matters, and what can be done about it.
Lori L. Burrows, Professor of Biocchemistry and Biomedical Sciences, McMaster University
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/125813
2019-11-26T18:41:52Z
2019-11-26T18:41:52Z
Antibiotic resistant superbugs kill 32 plane-loads of people a week. We can all help fight back
<figure><img src="https://images.theconversation.com/files/303067/original/file-20191122-112975-1imzmd6.jpg?ixlib=rb-1.1.0&rect=8%2C17%2C5982%2C3970&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotics can be a wonder for treating bacterial infections – but we need to be cautious in how we use them.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>You might think antibiotic resistance is something to worry about in the distant future. But it’s already having a deadly impact today.</p>
<p>The number of people dying globally every week from antibiotic resistant infections is <a href="https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_final_report_EN.pdf?ua=1">equivalent to 32 Boeing 747s</a> full of people. And if that sounds scary, the projections for the future are even scarier.</p>
<p>On today’s episode of <a href="https://theconversation.com/au/podcasts/trust-me-podcast">Trust Me, I’m An Expert</a> we ask you to imagine a future where more and more antibiotics don’t work any more – and hear from researchers about how you can help scientists fight back.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/this-is-going-to-affect-how-we-determine-time-since-death-how-studying-body-donors-in-the-bush-is-changing-forensic-science-117662">'This is going to affect how we determine time since death': how studying body donors in the bush is changing forensic science</a>
</strong>
</em>
</p>
<hr>
<h2>New to podcasts?</h2>
<p>Podcasts are often best enjoyed using a podcast app. All iPhones come with the Apple Podcasts app already installed, or you may want to listen and subscribe on another app such as Pocket Casts (click <a href="https://pca.st/VTv7">here</a> to listen to Trust Me, I’m An Expert on Pocket Casts).</p>
<p>You can also hear us on Stitcher, Spotify or any of the apps below. Just pick a service from one of those listed below and click on the icon to find Trust Me, I’m An Expert.</p>
<p><a href="https://itunes.apple.com/au/podcast/trust-me-im-an-expert/id1290047736?mt=2&ign-mpt=uo%3D8"><img src="https://images.theconversation.com/files/233721/original/file-20180827-75984-1gfuvlr.png" alt="Listen on Apple Podcasts" width="268" height="68"></a> <a href="https://www.google.com/podcasts?feed=aHR0cHM6Ly90aGVjb252ZXJzYXRpb24uY29tL2F1L3BvZGNhc3RzL3RydXN0LW1lLXBvZGNhc3QucnNz"><img src="https://images.theconversation.com/files/233720/original/file-20180827-75978-3mdxcf.png" alt="" width="268" height="68"></a></p>
<p><a href="https://www.stitcher.com/podcast/the-conversation/trust-me-im-an-expert"><img src="https://images.theconversation.com/files/233716/original/file-20180827-75981-pdp50i.png" alt="Stitcher" width="300" height="88"></a> <a href="https://tunein.com/podcasts/News--Politics-Podcasts/Trust-Me-Im-An-Expert-p1035757/"><img src="https://images.theconversation.com/files/233723/original/file-20180827-75984-f0y2gb.png" alt="Listen on TuneIn" width="318" height="125"></a></p>
<p><a href="https://radiopublic.com/trust-me-im-an-expert-Wa3E5A"><img class="alignnone size-medium wp-image-152" src="https://images.theconversation.com/files/233717/original/file-20180827-75990-86y5tg.png?ixlib=rb-1.1.0&q=45&auto=format&w=268&fit=clip" alt="Listen on RadioPublic" width="268" height="87"></a> <a href="https://open.spotify.com/show/7myc7drbLJVaRitAMXLB7V"><img src="https://images.theconversation.com/files/237984/original/file-20180925-149976-1ks72uy.png?ixlib=rb-1.1.0&q=45&auto=format&w=268&fit=clip" width="268" height="82"></a> </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/trust-me-im-an-expert-what-science-says-about-how-to-lose-weight-and-whether-you-really-need-to-122635">Trust Me, I'm An Expert: what science says about how to lose weight and whether you really need to</a>
</strong>
</em>
</p>
<hr>
<p><strong>Additional audio</strong></p>
<p><em>Kindergarten by Unkle Ho, from <a href="https://www.elefanttraks.com/">Elefant Traks.</a></em></p>
<p><em><a href="https://freemusicarchive.org/music/Podington_Bear/Meet_Podington_Bear_Box_Set_Disc_1/07_Airliner">Airliner</a> by Podington Bear from Free Music Archive.</em></p>
<h2>Images</h2>
<p><em>Shutterstock</em></p><img src="https://counter.theconversation.com/content/125813/count.gif" alt="The Conversation" width="1" height="1" />
Antibiotic resistant infections already kill about 700,000 people globally every year. While scientists are racing to find new ways to fight superbugs, there's one thing you can do, too.
Sunanda Creagh, Senior Editor
Phoebe Roth, Deputy Health Editor
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/100654
2018-09-02T20:10:28Z
2018-09-02T20:10:28Z
Five of the scariest antibiotic-resistant bacteria in the past five years
<figure><img src="https://images.theconversation.com/files/233381/original/file-20180824-149493-1su86jt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">When bacteria change, antibiotics can stop working.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Nearly one million people die every year from bacterial infections that <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">cannot be treated with common antibiotics</a>. This is frightening because right now we don’t have any alternatives to these antibiotics.</p>
<p><a href="https://theconversation.com/we-know-why-bacteria-become-resistant-to-antibiotics-but-how-does-this-actually-happen-59891">Antibiotic resistance occurs</a> when bacteria change in a way that prevents the antibiotic from working. Changes in bacteria, known as resistance mechanisms, come in different forms and can be shared between different bacteria, spreading the problem.</p>
<p>Antibiotic resistance risks returning us to an age where even simple cuts and scrapes can become deadly. For a glimpse of what could be commonplace in our future, here are five of the scariest antibiotic resistant bacteria from the last five years.</p>
<hr>
<p>
<em>
<strong>
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>
</strong>
</em>
</p>
<hr>
<h2>1. Extensively drug-resistant <em>Salmonella typhi</em></h2>
<p>This highly contagious bacterium causes typhoid fever, a life-threatening infection that affects about 21 million people around the world every year. About <a href="https://www.sciencedirect.com/science/article/pii/S2214109X14703018">1% of those affected</a>, or 223,000 people, will die.</p>
<p>In November 2016, a <a href="http://mbio.asm.org/content/9/1/e00105-18">strain of <em>Salmonella typhi</em></a> emerged in Pakistan. It was resistant to five antibiotics, leaving only one oral antibiotic (azithromycin) able to treat it. Since then there have been 858 reported cases of this infection, resulting in four deaths in just one Pakistani province.</p>
<p>Worryingly, this strain of <em>Salmonella typhi</em> had changed from being multidrug-resistant (resistant to at least three classes of antibiotic) to extensively drug-resistant (resistant to all but two classes of antibiotic) in a single step. It achieved this by acquiring a piece of DNA, called a plasmid, which already contained all the new resistance genes it needed. </p>
<p>Even more concerning is that this strain is now only one step away from being untreatable with all available antibiotics by finding another plasmid with the resistance genes for the last two classes of antibiotic that can kill it.</p>
<h2>2. Extensively drug-resistant <em>Mycobacterium tuberculosis</em></h2>
<p><em>Mycobacterium tuberculosis</em> is the world’s leading infectious killer, causing more than <a href="http://www.who.int/news-room/fact-sheets/detail/tuberculosis">1.7 million deaths</a> every year. One of the reasons this bacteria is so deadly is its ability to hide inside our cells. This means that to treat tuberculosis infection, people are required to take four different antibiotics continuously for six months.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/233408/original/file-20180824-149490-hye8t4.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">An increasing number of infections are becoming resistant to antibiotics.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
</figcaption>
</figure>
<p>It’s estimated up to <a href="http://www.who.int/tb/publications/global_report/en/">13% of all new tuberculosis cases</a> are multidrug-resistant, with Europe, including Russia, seeing the highest number of these cases. This is alarming, as multidrug-resistant infections require treatment courses that are much longer (generally 18 to 24 months) and use antibiotics that are expensive and can be bad for the kidneys and other organs.</p>
<p>It’s now been found that 6% of these cases are actually extensively drug-resistant (resistant to all but two classes of antibiotic). With a treatment success rate of only 30%, the global spread of extensively drug-resistant tuberculosis to more than <a href="http://www.who.int/tb/areas-of-work/drug-resistant-tb/global-situation/en/">123 countries</a> is extremely concerning.</p>
<h2>3. Pandrug-resistant <em>Klebsiella pneumoniae</em></h2>
<p><em>Klebsiella pneumoniae</em> is a common bacterium found in the skin, intestines and soil. It causes a range of potentially deadly infections in people with compromised immune systems. As this bacterium is particularly prevalent in hospitals, it’s one of the most <a href="https://www.cdc.gov/drugresistance/biggest_threats.html">critical drug-resistant threats</a> to public health.</p>
<p>In 2013 there were 8,000 reports of multidrug-resistant <em>Klebsiella pneumoniae</em> in <a href="https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf#page=53">the United States alone</a>, with a death rate of <a href="https://www.ncbi.nlm.nih.gov/pubmed/27843749">50% for people with bloodstream infections</a>. </p>
<p>In 2016 a strain of <a href="https://www.cdc.gov/mmwr/volumes/66/wr/mm6601a7.htm"><em>Klebsiella pneumoniae</em> was identified</a> in the United States that was resistant to all 26 commonly available antibiotics (known as pandrug-resistant). The patient infected by this bacteria died due to a lack of alternative treatments.</p>
<p>This is not an isolated case; other bacteria are also becoming pandrug-resistant.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/antibiotic-resistance-sorry-not-my-problem-44011">Antibiotic resistance? Sorry, not my problem</a>
</strong>
</em>
</p>
<hr>
<h2>4. Pandrug-resistant <em>Pseudomonas aeruginosa</em></h2>
<p>Like <em>Klebsiella pneumoniae</em>, <em>Pseudomonas aeruginosa</em> is a commonly found bacterium that causes infections in people with compromised immune systems. Like <em>Klebsiella pneumoniae</em>, it’s particularly prevalent in hospitals. </p>
<p>In the United States, there are an estimated 51,000 health care-associated <em>Pseudomonas aeruginosa</em> infections each year, with around 400 causing death. In the past five years, <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/656611/ESPAUR_report_2017.pdf">29 cases</a> of pandrug-resistant <em>Pseudomonas aeruginosa</em> infection have been reported in hospitals in England.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/233407/original/file-20180824-149496-1viwwf9.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">People with weaker immune systems are more susceptible to infection.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
</figcaption>
</figure>
<p><em>Pseudomonas aeruginosa</em> infection is also the leading cause of death for people with cystic fibrosis. In 2013, more than 42% of cystic fibrosis patients with chronic <em>Pseudomonas aeruginosa</em> infection were <a href="https://www.cysticfibrosis.org.uk/the-work-we-do/uk-cf-registry/reporting-and-resources">treated with colistin</a>, the “last line of defence” antibiotic. This is because most of these infections were resistant to every other antibiotic available.</p>
<h2>5. Extensively drug-resistant <em>Neisseria gonorrhoeae</em></h2>
<p>There are an estimated <a href="http://www.who.int/news-room/detail/07-07-2017-antibiotic-resistant-gonorrhoea-on-the-rise-new-drugs-needed">78 million global cases</a> of <em>Neisseria gonorrhoeae</em>, which causes gonorrhoea, a sexually transmitted infection affecting men and women. Although usually not deadly, serious and permanent health problems including infertility can result if the disease goes untreated.</p>
<p>Around one-third of all <em>Neisseria gonorrhoeae</em> infections are resistant to at least one antibiotic. More worryingly, a new extensively drug-resistant <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/701185/hpr1418_MDRGC.pdf">“super gonorrhoeae”</a>, resistant to all but one antibiotic, has been discovered. </p>
<p>Two of the first reported cases of this superbug were in Australia. This is cause for concern, as extensively drug-resistant <em>Neisseria gonorrhoeae</em> can spread quickly through a population if people have multiple partners. In rare cases, untreated gonorrhoea can enter the bloodstream, causing septic shock and death.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/when-the-drugs-dont-work-how-we-can-turn-the-tide-of-antimicrobial-resistance-71711">When the drugs don’t work: how we can turn the tide of antimicrobial resistance</a>
</strong>
</em>
</p>
<hr>
<h2>Could future outbreaks be worse?</h2>
<p>Yes. Bacteria have the ability to pass antibiotic resistance genes to other bacteria and can develop the resistance themselves. So it’s likely a bacteria resistant to all but one antibiotic will develop resistance to that final one over time. </p>
<p>The good news is we can reduce the likelihood of this happening if we use antibiotics appropriately and invest in the research and development of new antibiotics, vaccines and diagnostic tools.</p><img src="https://counter.theconversation.com/content/100654/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Laura Christine McCaughey receives funding from The Wellcome Trust. </span></em></p>
Antibiotic resistance is a major and growing global health threat. These five recent examples show us how dangerous it can be.
Laura Christine McCaughey, Research Fellow in Microbiology, University of Technology Sydney
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/94302
2018-04-05T06:41:03Z
2018-04-05T06:41:03Z
‘Super gonorrhoea’ raises the stakes in the war against superbugs
<figure><img src="https://images.theconversation.com/files/213320/original/file-20180405-189798-nbplrq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotic resistance is not new but recent developments increase the urgency for action.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>There has been a lot of news over the past few weeks about the rise of superbugs and antibiotic overuse, including a <a href="https://www.theguardian.com/commentisfree/2018/mar/30/super-gonorrhoea-antibiotic-crisis-drug-resistant-bugs">nasty sexually transmitted infection</a> in the United Kingdom. A British man is the first in the world to be diagnosed with a strain of gonorrhoea resistant to all strains of antibiotics used to treat the infection. </p>
<p>Superbugs have tended to pose the greatest risk to people with compromised immune systems, such as cancer patients, and those who were injured or underwent surgery. But the sexual transmission of these bugs means antibiotic resistant infections can spread much more widely.</p>
<p>So what exactly are superbugs, and how scared should we be?</p>
<h2>Super but not new</h2>
<p>“Superbugs” aren’t the bug equivalent of superheroes. The term describes bacteria that have become resistant to antibiotics. How “super” they are depends on how many antibiotics they have become resistant to. </p>
<p>“Antibiotic resistance” and “drug-resistant infections” also refer to the same phenomena. They describe microorganisms that have evolved to become impervious to being killed by treatment with antibiotics. </p>
<p>There is a common misconception that antibiotic resistance means your body has become resistant to antibiotics. This is not true.</p>
<p>Antibiotic resistance is nothing new. Alexander Fleming’s 1945 <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf">Nobel Prize acceptance speech for the discovery of penicillin</a> discusses the development of resistance. He includes a scenario of Patient X, who:</p>
<blockquote>
<p>buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin. He then infects his wife. Mrs. X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails.</p>
</blockquote>
<p>Indeed, resistance has been reported for <em>every</em> antibiotic ever introduced – <a href="https://antimicrobialresistance101.files.wordpress.com/2015/04/antibiotic-resistance-history-graph.png">generally within a few years</a> of deployment.</p>
<h2>How do they become resistant?</h2>
<p>Bacteria are able to fight antibiotics by a variety of methods:</p>
<ul>
<li>They build stronger cell walls to stop the drugs from entering</li>
<li>They actively spit them out so the antibiotic can’t reach a lethal concentration inside the cell</li>
<li>They produce enzymes that modify and inactivate the antibiotics and</li>
<li>They alter the target of the antibiotic so it no longer interacts with the drug.</li>
</ul>
<p>One or more of these resistance mechanisms may already be naturally present in a very small fraction of the millions of bacteria exposed to an antibiotic. This is called “innate resistance”. Most of the bacteria are killed, but this small population survives and grows. </p>
<p>In other cases, resistance develops through evolution (a process known as “induced resistance”). Bacteria grow rapidly. Under optimal conditions the population can double in as few as 15-30 minutes. </p>
<p>When exposed to sub-lethal doses of antibiotic, bacteria can become tolerant. They accumulate beneficial mutations over multiple generations. They then pass on this resistance to their progeny when they divide.</p>
<hr>
<p>
<em>
<strong>
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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</em>
</p>
<hr>
<p>Bacteria are also very promiscuous. They exchange pieces of genetic material (plasmids) that carry the codes for resistance. This allows for the rapid spread of resistance between different types of bacteria. </p>
<p>An example is highlighted by <a href="https://www.theaustralian.com.au/news/world/the-times/drug-resistance-spreads-to-humans-at-shocking-rate/news-story/fc0d3487e6f353a1f4569c1770721d34">recent news reports</a> of resistance to a “last resort” antibiotic, colistin. A gene called mcr-1 (mobilized colistin resistance) was found to be contained in plasmids in <em>E. coli</em> bacteria collected from Chinese pig farms in 2011 (<a href="http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00424-7/fulltext">though it was not reported until 2015</a>). </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/213326/original/file-20180405-189816-h2h0lq.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">A gene that makes bugs resistant to antibiotics of ‘last resort’ was found in Chinese pig farms.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/1060871903?src=8TKC8hWSjSmYq38tXIvwjw-1-22&size=medium_jpg">Zawinul/Shutterstock</a></span>
</figcaption>
</figure>
<p>While colistin resistance was already known, the potential for resistance to be quickly spread by this new mechanism is of great concern. For some infections, colistin is the only antibiotic that still works. Indeed, the mcr-1 gene has now been found in <a href="https://www.nature.com/articles/s41467-018-03205-z">multiple types of bacteria in more than 30 countries</a> (including a <a href="http://www.cidrap.umn.edu/news-perspective/2016/05/highly-resistant-mcr-1-superbug-found-us-first-time">patient in the United States in 2016</a>).</p>
<p>The <a href="http://www.searo.who.int/mediacentre/releases/2015/1612/en/">World Health Organisation is now warning</a> that we face a return to a “pre-antibotic era”. It warns:</p>
<blockquote>
<p>Common infections and minor injuries which have been possible to treat for decades may once again kill millions. Resistance to antibiotics will make complex surgeries and management of several chronic illnesses like cancer extremely difficult.</p>
</blockquote>
<p>Before antibiotics, 40% of deaths were due to infection. If we do not act, <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">a review commissioned by the United Kingdom government</a> predicts that by 2050 drug-resistant infections could cause 10 million annual deaths.</p>
<h2>How did we get here?</h2>
<p>This rise in resistance is largely driven by excessive antibiotic use. The same UK report indicates that up to two-thirds of the world’s antibiotics are not used to treat humans, but are given to animals grown for food. This animal use is often as a food additive, not as therapeutic treatment for an infection. </p>
<p>Of the remaining antibiotics used in humans, up to two-thirds may be inappropriately prescribed. </p>
<p>This huge overuse of antibiotics inevitably drives the development of resistance by unnecessarily exposing a much greater population of bacteria to antibiotics. Sub-lethal concentrations, such as in waste water from farms, fosters resistance. </p>
<p>Alarmingly, <a href="http://www.pnas.org/content/early/2018/03/20/1717295115">a recent study</a> shows that <a href="https://www.theguardian.com/science/2018/mar/26/calls-to-rein-in-antibiotic-use-after-study-shows-65-increase-worldwide">our use of antibiotics is increasing even more</a>.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-the-health-and-agriculture-sectors-need-to-work-together-to-stop-antibiotic-resistance-69031">Why the health and agriculture sectors need to work together to stop antibiotic resistance</a>
</strong>
</em>
</p>
<hr>
<p>So, given we already have <a href="https://www.statnews.com/2017/01/12/nevada-woman-superbug-resistant/">people dying from bacteria resistant to all known antibiotics</a>, and these bacteria are <a href="https://apnews.com/afcee30eb24848d38f9b855fbcc9a4ba">becoming increasingly prevalent</a>, what’s stopping a global pandemic tomorrow? </p>
<p>It really comes down to the fact that, unless you’re immunocompromised or have an injury allowing the bacteria to get into your body, most bacteria aren’t particularly effective at spreading infections. </p>
<p>This is why the <a href="https://news.nationalgeographic.com/2018/03/gonorrhea-evolving-untreatable-spd/">reports</a> of a <a href="https://www.theguardian.com/commentisfree/2018/mar/30/super-gonorrhoea-antibiotic-crisis-drug-resistant-bugs">“super-gonorrhea” case in the UK </a> are alarming. The sexually transmitted bacteria (<em>Neisseria gonorrhoeae</em>) <a href="http://www.who.int/mediacentre/news/releases/2017/Antibiotic-resistant-gonorrhoea/en/">causes nearly 80 million infections a year</a>. This bacteria now has the potential to carry and spread high levels of antibiotic resistance through a much larger population of both people and other bacteria.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/213325/original/file-20180405-189821-p2j2no.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">Super-gonorrhea has the potential to spread antibiotic resistance to many more people.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/white-mattress-after-waking-morning-sun-1058016380?src=idJzfv5Tw4DqSyPgT08sBA-1-42">The Five Aggregates/Shutterstock</a></span>
</figcaption>
</figure>
<h2>Fight against superbugs</h2>
<p>It’s not all doom and gloom. Nations and international organisations are increasingly devoting attention and resources to fight the rise of antibiotic resistance. Strategies include more sparing use of existing antibiotics, and <a href="https://longitudeprize.org/">investment and incentives to develop diagnostics</a> that can decide when antibiotics are needed.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/when-the-drugs-dont-work-how-we-can-turn-the-tide-of-antimicrobial-resistance-71711">When the drugs don’t work: how we can turn the tide of antimicrobial resistance</a>
</strong>
</em>
</p>
<hr>
<p>Non-antibiotic approaches, such as vaccines, phage therapy, and microbiome manipulation, are garnering increased consideration. </p>
<p>Initiatives to re-invigorate the discovery of new antibiotics include efforts such as <a href="https://www.gardp.org/">The Global Antibiotic Research & Development Partnership</a>, the <a href="http://www.carb-x.org/">Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator</a>, and Australia’s own global effort to crowdsource antibiotics from international chemists, <a href="http://www.co-add.org">The Community for Open Antimicrobial Drug Discovery</a>. </p>
<p>We must keep our attention on the threat posed by drug resistant infections and invest in antimicrobial research to keep the potential global catastrophe at bay.</p><img src="https://counter.theconversation.com/content/94302/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Blaskovich receives funding from the NHMRC, Australian Academy of Technology and Engineering, the Aiustralian Department of Industry, Innovation and Science, and the Wellcome Trust for antibiotic-related research. He works for the Community for Open Antimicrobial Drug Discovery, an initiative to discover new antibiotics. He is an inventor on several patents describing new antibiotics.</span></em></p>
Superbugs used to pose the greatest risk to people with compromised immune systems and those who had surgery. But their sexual transmission means antibiotic resistance can spread much more widely.
Mark Blaskovich, Senior Research Officer, The University of Queensland
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/74490
2017-04-17T22:56:16Z
2017-04-17T22:56:16Z
Medieval medical books could hold the recipe for new antibiotics
<figure><img src="https://images.theconversation.com/files/165279/original/image-20170413-11758-10u9ffg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A recipe for an eyesalve from 'Bald's Leechbook.'</span> <span class="attribution"><span class="source">© The British Library Board (Royal MS 12 D xvii)</span></span></figcaption></figure><p>For a long time, medieval medicine has been dismissed as irrelevant. This time period is popularly referred to as the “Dark Ages,” which erroneously suggests that it was unenlightened by science or reason. However, some medievalists and scientists are now looking back to history for clues to inform the search for new antibiotics.</p>
<p>The evolution of <a href="http://www.who.int/mediacentre/factsheets/fs194/en/">antibiotic-resistant microbes</a> means that it is always necessary to find new drugs to battle microbes that are no longer treatable with current antibiotics. But progress in finding new antibiotics is slow. The drug discovery pipeline is currently stalled. <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">An estimated 700,000 people</a> around the world die annually from drug-resistant infections. If the situation does not change, it is estimated that such infections will kill 10 million people per year by 2050.</p>
<p>I am part of the <a href="https://www.nottingham.ac.uk/news/pressreleases/2015/march/ancientbiotics---a-medieval-remedy-for-modern-day-superbugs.aspx">Ancientbiotics team</a>, a group of medievalists, microbiologists, medicinal chemists, parasitologists, pharmacists and data scientists from multiple universities and countries. We believe that answers to the antibiotic crisis could be found in medical history. With the aid of modern technologies, we hope to unravel how premodern physicians treated infection and whether their cures really worked. </p>
<p>To that end, we are compiling a database of medieval medical recipes. By revealing patterns in medieval medical practice, our database could inform future laboratory research into the materials used to treat infection in the past. To our knowledge, this is the first attempt to create a medieval medicines database in this manner and for this purpose. </p>
<h2>Bald’s eyesalve</h2>
<p>In 2015, our team published a <a href="http://mbio.asm.org/content/6/4/e01129-15.full">pilot study</a> on a 1,000-year old recipe called Bald’s eyesalve from <a href="http://blogs.bl.uk/digitisedmanuscripts/2016/01/balds-leechbook-now-online.html">“Bald’s Leechbook,”</a> an Old English medical text. The eyesalve was to be used against a “wen,” which may be translated as a sty, or an infection of the eyelash follicle. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=625&fit=crop&dpr=1 600w, https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=625&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=625&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=785&fit=crop&dpr=1 754w, https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=785&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/164606/original/image-20170410-29390-1gtp4f5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=785&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Human white blood cells (in blue) take on <em>Staphylococcus aureus</em> bacteria.</span>
<span class="attribution"><a class="source" href="https://phil.cdc.gov/phil/details.asp?pid=18140">Frank DeLeo, National Institute of Allergy and Infectious Diseases</a></span>
</figcaption>
</figure>
<p>A common cause of modern styes is the bacterium <a href="https://www.cdc.gov/hai/organisms/staph.html"><em>Staphylococcus aureus</em></a>. <a href="https://www.cdc.gov/mrsa/">Methicillin-resistant <em>Staphylococcus aureus</em> (or MRSA)</a> is resistant to many current antibiotics. Staph and MRSA infections are responsible for a variety of severe and chronic infections, including wound infections, sepsis and pneumonia. </p>
<p>Bald’s eyesalve contains wine, garlic, an <em>Allium</em> species (such as leek or onion) and oxgall. The recipe states that, after the ingredients have been mixed together, they must stand in a brass vessel for nine nights before use. </p>
<p>In <a href="http://mbio.asm.org/content/6/4/e01129-15.full">our study</a>, this recipe turned out to be a potent antistaphylococcal agent, which repeatedly killed established <a href="http://www.radiolab.org/story/best-medicine/"><em>S. aureus</em></a> <a href="https://wwwnc.cdc.gov/eid/article/8/9/02-0063_article">biofilms</a> – a sticky matrix of bacteria adhered to a surface – in an in vitro infection model. It also killed MRSA in mouse chronic wound models.</p>
<h2>Medieval methods</h2>
<p>Premodern European medicine has been poorly studied for its clinical potential, compared with traditional pharmacopeias of other parts of the world. Our research also raises questions about medieval medical practitioners. Today, the word “medieval” is used as a derogatory term, indicating cruel behavior, ignorance or backwards thinking. This perpetuates the myth that the period is unworthy of study. </p>
<p>During our eyesalve study, chemist Tu Youyou was awarded the <a href="https://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.html">Nobel Prize in Physiology or Medicine</a> for her discovery of a new therapy for malaria after searching over 2,000 recipes from ancient Chinese literature on herbal medicine. Is another “silver bullet” for microbial infection hidden within medieval European medical literature?</p>
<p>Certainly, there are medieval superstitions and treatments that we would not replicate today, such as purging a patient’s body of pathogenic humors. However, <a href="http://www.loc.gov/preservation/outreach/tops/connelly/index.html">our work</a> suggests that there could be a methodology behind the medicines of medieval practitioners, informed by a long tradition of observation and experimentation. </p>
<p>One key finding was that following the steps exactly as specified by the Bald’s eyesalve recipe – including waiting nine days before use – was crucial for its efficacy. Are the results of this medieval recipe representative of others that treat infection? Were practitioners selecting and combining materials following some “scientific” methodology for producing biologically active cocktails? </p>
<p>Further research may show that some medieval medicines were more than placebos or palliative aids, but actual “ancientbiotics” used long before the modern science of infection control. This idea underlies our current study on the medieval medical text, “Lylye of Medicynes.” </p>
<h2>A medieval medicines database</h2>
<p>The “Lylye of Medicynes” is a 15th-century Middle English translation of the Latin “Lilium medicinae,” first completed in 1305. It is a translation of the major work of a significant medieval physician, <a href="https://www.amazon.com/Doctor-Bernard-Gordon-Studies-Texts/dp/0888440510">Bernard of Gordon</a>. His “Lilium medicinae” was translated and printed continuously over many centuries, until at least the late 17th century.</p>
<p>The text contains a wealth of medical recipes. In the Middle English translation, there are 360 recipes – clearly indicated with Rx in the text – and many thousands more ingredient names. </p>
<p>As a doctoral student, I prepared the first-ever edition of the “Lylye of Medicynes” and compared the recipes against four extant Latin copies of the “Lilium medicinae.” This involved faithfully copying the Middle English text from the medieval manuscript, then editing that text for a modern reader, such as adding modern punctuation and correcting scribal errors. The “Lylye of Medicynes” is 245 folios, which equates to 600 pages of word-processed text. </p>
<p>I loaded the Middle English names of ingredients into a database, along with translations into modern equivalents, juxtaposed with relationships to recipe and disease. It is very time-consuming to format medieval data for processing with modern technologies. It also takes time to translate medieval medical ingredients into modern equivalents, due in part to multiple synonyms as well as variations in modern scientific nomenclature for plants. This information has to be verified across many sources. </p>
<p>With our database, we aim to find combinations of ingredients that occur repeatedly and are specifically used to treat infectious diseases. To achieve this, we are employing some common tools of data science, such as <a href="http://epubs.siam.org/doi/pdf/10.1137/S003614450342480">network analysis</a>, a mathematical method to examine the relationships between entries. Our team will then examine how these patterns may help us to use medieval texts as inspiration for lab tests of candidate “ancientbiotic” recipes. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=222&fit=crop&dpr=1 600w, https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=222&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=222&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=279&fit=crop&dpr=1 754w, https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=279&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/164608/original/image-20170410-7394-1xdr57r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=279&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Word cloud from the Lylye of Medicynes.</span>
<span class="attribution"><span class="source">Erin Connelly</span></span>
</figcaption>
</figure>
<p>In March, we tested a small portion of the database to ensure that the method we developed was appropriate for this data set. At present, the database contains only the 360 recipes indicated with Rx. Now that the proof-of-concept stage is complete, I will expand the database to contain other ingredients which are clearly in recipe format, but may not be marked with Rx. </p>
<p>We are specifically interested in recipes associated with recognizable signs of infection. With Bald’s eyesalve, the combination of ingredients proved to be crucial. By examining the strength of ingredient relationships, we hope to find out whether medieval medical recipes are driven by certain combinations of antimicrobial ingredients. </p>
<p>The database could direct us to new recipes to test in the lab in our search for novel antibiotics, as well as inform new research into the antimicrobial agents contained in these ingredients on the molecular level. It could also deepen our understanding of how medieval practitioners “designed” recipes. Our research is in the beginning stages, but it holds exciting potential for the future.</p><img src="https://counter.theconversation.com/content/74490/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Erin Connelly 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>
A team of medievalists and scientists look back to history – including a 1,000-year-old eyesalve recipe – for clues to new antibiotics.
Erin Connelly, CLIR-Mellon Fellow for Data Curation in Medieval Studies, University of Pennsylvania
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/53855
2016-03-21T10:12:46Z
2016-03-21T10:12:46Z
Fighting superbugs with nanotechnology and light
<figure><img src="https://images.theconversation.com/files/114996/original/image-20160314-11277-1jdarwf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A quantum dot: A high-resolution transmission electron micrograph of cadmium telluride nanoparticles. (The scale bar in the lower right is 2 nanometers long, or two millionths of a millimeter.)</span> <span class="attribution"><span class="source">Nagpal Group, University of Colorado</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span></figcaption></figure><p>A new tool is emerging in the fight against antibiotic-resistant bacterial disease. Beyond the global efforts to limit overuse and abuse of antibiotic drugs, nanomedicine is finding additional ways to attack these superbugs.</p>
<p>Nanoparticles, a million times smaller than a millimeter, are proving to be stable, easy to deliver and readily incorporated into cells.</p>
<p>In recent work, a group of researchers at the University of Colorado, of which I am a member, has used nanoscale quantum dots – minuscule semiconductor particles with specific light-absorption properties – to <a href="http://www.nature.com/nmat/journal/vaop/ncurrent/full/nmat4542.html">kill drug-resistant superbugs</a> without harming the surrounding healthy tissue. </p>
<p>Once introduced into the body, the quantum dots do nothing until they are activated by having a light shined on them. Any visible light source (a lamp, room light or even sunlight) can be used for this. So far our research has focused on topical infections on the skin; deeper inside the body, brighter lights or more nanoparticles may be needed.</p>
<p>When activated by light, the quantum dots start generating electrons that attach to dissolved oxygen in the cells, creating radical ions. Those ions interrupt biochemical reactions which cells rely on for communication and basic life functions. In this way, we can target and kill very specific bacterial cells that cause illnesses.</p>
<h2>The superbug threat</h2>
<p>Antibiotics are used not just to treat active bacterial infections; they are also routinely given to patients undergoing surgery, and people with compromised immune systems from diseases like HIV and cancer.</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=229&fit=crop&dpr=1 600w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=229&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=229&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=288&fit=crop&dpr=1 754w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=288&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/114985/original/image-20160314-11264-1sn59eb.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=288&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">What a superbug looks like: A modified atomic-force micrograph of multi drug-resistant E. coli.</span>
<span class="attribution"><span class="source">Nagpal Group, University of Colorado</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Bacteria that are resistant to more than one antibiotic drug – or “superbugs,” as they are commonly called – infect <a href="http://www.cdc.gov/drugresistance/">more than 2 million Americans a year</a>, and kill 23,000 of them. Globally, they <a href="http://amr-review.org/">kill more than 700,000 people</a> each year.</p>
<p>Projections by a <a href="http://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf">United Kingdom government research panel</a> suggest that if unchecked, superbugs could <a href="http://www.scientificamerican.com/article/antibiotic-resistance-will-kill-300-million-people-by-2050/">kill more than 10 million people each year by 2050</a>. That would far outpace all other major causes of death – including diabetes, cancer, diarrhea and road accidents. The economic cost is estimated at <a href="http://amr-review.org/">US$100 trillion</a> by 2050.</p>
<h2>Focusing on a target</h2>
<p>There are other nano-scale medicines for fighting infectious bacteria. When exposed to light, they heat up, killing all cells around them – not just the <a href="http://www.etp-nanomedicine.eu/public/about-nanomedicine/nanomedicine-applications/nanomedicine-in-cancer">disease-causing ones</a>. They therefore require special tools such as proteins or antibodies that selectively stick to desired cell types, to deliver them to very specific locations. That in turn requires the ability to accurately identify target cells.</p>
<p>Our method is an improvement because it allows more specific targeting of cells to be treated. Quantum dots with different sizes and electrical properties can help create different disruptive ions. That can allow doctors to choose disruptors to kill invading bacteria without harming nearby healthy tissue.</p>
<p>The activated quantum dots upset the balance of chemical processes, called “reduction-oxidation” or “<a href="http://www.wiley.com/college/boyer/0470003790/reviews/redox/redox.htm">redox</a>” for short, in disease-causing bacteria in order to kill them.</p>
<p>Using this method and only a normal light bulb, we were able to eliminate a broad range of antibiotic-resistant bacteria. The bacteria were provided to us in the form of actual clinical samples from the <a href="http://www.ucdenver.edu/academics/colleges/medicalschool/Pages/somWelcome.aspx">University of Colorado School of Medicine</a>. They included some of the most dangerous drug-resistant infections: methicillin-resistant <em>Staphylococcus aureus</em>; extended-spectrum β-lactamase-producing <em>Klebsiella pneumoniae</em> and <em>Salmonella typhimurium</em>; multi-drug-resistant <em>Escherichia coli</em>; and carbapenem-resistant <em>Escherichia coli</em>. </p>
<p>We were also able to make nanoparticles with different reactions to light, including having no response or even improving cellular reproduction. Increasing the growth of superbugs is not desirable, but this discovery may allow us encourage the growth of useful bacteria, such as in <a href="http://www.biotopics.co.uk/microbes/penici.html">bioreactors</a>, which can help manufacture of biofuels and antibiotic drugs.</p>
<h2>Taking the next steps</h2>
<p>So far our work has been in test tubes in controlled labs; our next step is to study this technique in animals. If successful, this technology could boost the fight against multi-drug-resistant bacteria in the short term and well out into the future.</p>
<p>It might, for example, spur the creation of a new class of light-activated drugs, lead to development of special fabrics with LED lights for phototherapy, and even form the basis of self-disinfecting surfaces and medical equipment.</p>
<p>And while the bacteria will continue to evolve to seek survival, our ability to control the specific reaction of the quantum dots once activated could let us move more quickly in this fight where defeat is not an option.</p><img src="https://counter.theconversation.com/content/53855/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Prashant Nagpal receives funding from National Science Foundation and William M. Keck Foundation.</span></em></p>
Quantum dots - minuscule semiconductor particles with specific light-absorption properties - can kill drug-resistant superbugs without harming the surrounding healthy tissue.
Prashant Nagpal, Assistant Professor of Chemical and Biological Engineering, University of Colorado Boulder
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/46224
2015-08-18T05:32:14Z
2015-08-18T05:32:14Z
How DNA detectives are helping solve the rise of superbugs
<figure><img src="https://images.theconversation.com/files/92167/original/image-20150817-28357-187tg5c.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">royaltystockphoto.com/</span></span></figcaption></figure><p>It is now 12 years since the first set of genetic instructions in a human <a href="https://www.genome.gov/11006929">was sequenced</a>. Many of our hopes for using knowledge about the human genome to better fight the likes of heart disease and cancer still lie years and decades in the future, but DNA sequencing in healthcare is not all about tomorrow. It is already revolutionising clinical microbiology. Most exciting of all, it is giving us an important tool in our battle with drug-resistant strains of bacteria. These strains are one of the <a href="http://www.bbc.co.uk/news/health-27204988">major growing threats</a> to human health, and have <a href="http://www.independent.co.uk/life-style/health-and-families/health-news/soft-touch-gps-told-to-stop-giving-antibiotics-to-pushy-patients-so-as-to-curb-rise-of-drugresistant-superbugs-10459183.html">just prompted</a> new guidelines in the UK on how GPs should prescribe antibiotics. </p>
<p>Clinical microbiology is the branch of medicine concerned with preventing and treating infectious diseases. It depends on rapidly identifying the pathogens that cause illness – bacteria, virus and fungus. Identification makes it possible to treat patients individually and monitor the outbreak and spread of a disease effectively. </p>
<p>The traditional way of identifying most bacterial pathogens is to grow a patient’s specimen in a culture, testing its susceptibility to antimicrobial drugs and comparing it with other bacterial strains. It <a href="http://www.nature.com/news/health-care-bring-microbial-sequencing-to-hospitals-1.15282">can take</a> days in the case of rapidly growing bacteria such as <em>E.coli</em>, and months in the case of slower developers like <em>Mycobacterium tuberculosis</em>.</p>
<p>In the early years of the 21st century <a href="http://www.sciencedirect.com/science/article/pii/S1198743X14631979">there were</a> some major technical advances in this field, but challenges remain. Identifying the exact strain of pathogen continues to be difficult, while there are also many obstacles to tracking their routes of transmission and monitoring mutations. </p>
<p>DNA sequencing could well be the answer. Developed in 1975 by a group led by Fred Sanger – whose work is the subject of a <a href="http://www.whatisbiotechnology.org/exhibitions/sanger">new online exhibition</a> – DNA sequencing was not routinely used in clinical microbiological laboratories until very recently. It was very expensive and entailed laborious manual laboratory work and painstaking reading of the results. Yet cheaper rapid DNA sequencers and large reference databases are increasingly changing this situation. </p>
<p>The <a href="http://www.nature.com/nrg/journal/v13/n9/full/nrg3226.html">average cost</a> of bench-top sequencers is now US$125,000 (£80,000). Such machines can sequence several bacterial genomes in a day at a cost of about $150 per sample. As recently as 2007 the cost of sequencing just one bacterial genome could be $800,000. It is <a href="http://genome.wellcome.ac.uk/doc_WTX056439.html">now possible</a> to sequence 100 bacterial genomes in a single run. </p>
<h2>Rosie Hospital</h2>
<p>The technology’s potential with drug-resistant infections first <a href="http://www.independent.co.uk/life-style/health-and-families/health-news/mrsa-outbreak-at-cambridges-rosie-hospital-halted-by-new-dna-profiling-technology-8315755.html">came to the fore</a> during an MRSA outbreak at the Rosie Hospital in Cambridge, UK in 2011. When three babies all tested positive at the same time in the baby unit, the hospital’s infection-control team reviewed the previous six months’ records and found babies had been infected sporadically by MRSA – sometimes months apart. </p>
<p>But was this an outbreak of MRSA or merely unrelated infections? Since conventional methods were little help, experts in whole genome sequencing at the <a href="https://www.sanger.ac.uk">Wellcome Trust Sanger Institute</a> and Cambridge University were called in. They quickly established that the samples were all related at the genome level, suggesting an outbreak. By sequencing other bacteria in the hospital’s microbiology laboratory database with the same antibiotic susceptibility profile, <a href="http://www.thenakedscientists.com/HTML/interviews/interview/1000023/">they confirmed</a> this was a new strain of MRSA with twice as many infections as first thought and that it was also prevalent in the wider community. </p>
<p>Two months after the previous infections were discovered, another baby tested positive despite the unit having just been thoroughly cleaned. So the team sequenced bacteria from swabs taken from staff on the unit and discovered that a particular individual was carrying the same strain of MRSA. Once that staff member was treated, the outbreak ended.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/92123/original/image-20150817-5121-1ht1pqy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">MRSA free thanks to DNA sequencing: Rosie Hospital, Cambridge.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/shelley_dave/2782342702/in/photolist-2jCbxs-2jCedu-2jCd5J-2jxUCP-2jCfqw-5eSexU-dCtqD1-dCtqFs-dCtqHG">Dave Gunn</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<h2>Developments since</h2>
<p>There was much talk at the time about the potential for this success to be duplicated elsewhere – and this looks to be bearing out. In 2014 the same Cambridge team <a href="http://www.cam.ac.uk/research/news/using-genome-sequencing-to-track-mrsa-in-under-resourced-hospitals">working together</a> with researchers from Thailand and Australia demonstrated using whole genome sequencing to track and identify MRSA on two intensive-care units in an under-resourced hospital in north-east Thailand. </p>
<p>What was striking was how many different variants of the infection the team detected in the hospital at the same time, something conventional typing had failed to pick up. The work also helped identify clinically important genes such as those coding for antiseptic resistance and antibiotic resistance. Drug-resistant bacteria <a href="http://genome.cshlp.org/content/early/2014/12/01/gr.174730.114">are particularly</a> a problem in poorer countries, so the results looked especially important. </p>
<p>Beyond MRSA, <a href="http://www.genomemedicine.com/content/6/11/70">whole genome sequencing thwarted</a> another type of drug-resistant bacteria at the Queen Elizabeth Hospital in Birmingham, UK in 2013. This was an outbreak of <em>Acinetobacter baumannii</em>, an opportunistic bacteria which causes pneumonia and bloodstream infections in critically ill patients with compromised immune systems. A new strain of the bacteria had been plaguing the hospital for more than 18 months. Once it was sequenced, researchers at Warwick and Birmingham universities were able to show that the previous theory that the infection was being transmitted within one ward had been wrong: they were picking it up from a specialised burns-care bed elsewhere. </p>
<p>This year Imperial College London researchers <a href="http://wwwnc.cdc.gov/eid/article/21/6/14-1903_article">were able</a> to solve a tuberculosis mystery concerning two patients who had contracted drug-resistant strains of the infection. The first had worked in healthcare in South Africa in an area where there had been a serious outbreak of drug-resistant TB in 2005, but had been healthy when coming to England. The second had never travelled abroad and, as is common with TB, experienced no symptoms for four years. It was only through whole genome sequencing that they could be linked together: it turned out they had spent eight days on the same medical ward in 2008. With drug-resistant TB <a href="http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_23-3-2015-14-36-31">cases rising</a> in the UK from 28 cases in 2000 to 81 in 2012, this too is an important development. </p>
<p>Despite all these positives, a major obstacle <a href="http://www.nature.com/news/health-care-bring-microbial-sequencing-to-hospitals-1.15282">blocks the</a> widespread adoption of whole genome sequencing against drug-resistant bacteria. Currently there are few tools to automatically analyse and interpret sequenced data from clinical samples so that it can be understood and clinically applied by non-specialists. This makes it difficult to roll out the system and prevents costs from falling even lower. </p>
<p>Stanford University in California might be pointing the way to a solution, however. Researchers there <a href="http://hivdb.stanford.edu/DR/webservices/">have</a> developed a web-based system for tracking drug-resistant HIV. If this can be applied to other infections, including bacterial ones, genome sequencing could become routine in hospitals worldwide.</p><img src="https://counter.theconversation.com/content/46224/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Lara has received funding from the UK Medical Research Council. She has research affiliations with Cambridge University, King's College London and University College London.</span></em></p>
While many of the fruits of the human genome project could be decades away, DNA sequencing of drug-resistant bacteria has been striding forwards
Lara Marks, University of Cambridge
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/41391
2015-05-07T15:58:25Z
2015-05-07T15:58:25Z
The answer to tackling superbugs could be … more superbugs
<figure><img src="https://images.theconversation.com/files/80833/original/image-20150507-1245-vsimbg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Antibiotic-resistant bacteria are a leading cause of hospital infections.</span> <span class="attribution"><span class="source">from www.shutterstock.com</span></span></figcaption></figure><p>Hard-to-kill bacteria or “superbugs” have become a major problem for hospitals. Between 5% and 12% of hospital patients in the EU are thought to acquire an infection <a href="http://ec.europa.eu/health/antimicrobial_resistance/policy/index_en.htm">during their stay</a>, with many caused by bacteria such as <em>Clostridium difficile</em> (<em>C. diff</em>) that are resistant to antibiotics.</p>
<p>In the US, <em>C. diff</em> is the <a href="http://www.ncbi.nlm.nih.gov/pubmed/25714160">leading cause</a> of hospital-acquired infections and, in the UK – although it is declining – it remains a major healthcare problem implicated in <a href="https://www.gov.uk/government/statistics/clostridium-difficile-infection-annual-data">thousands of deaths</a> every year. But a group of researchers believe they may have found <a href="http://www.bbc.co.uk/news/health-32551873%20http://jama.jamanetwork.com/article.aspx?articleid=2281703">a surprising answer</a> to treating <em>C. diff</em>: giving patients another dose of the bacterium.</p>
<p>The effects of <em>C. diff</em> range from mild diarrhoea to more serious and life-threatening conditions such as pseudomembraneous colitis (inflammation of the intestines) and toxic megacolon, which often require surgery to remove the affected tissue and can be fatal.</p>
<p>Despite being a major human pathogen, <em>C. diff</em> is actually part of the normal group of microorganisms found in the gut (<a href="http://www.ncbi.nlm.nih.gov/pubmed/25595843">in 3% of healthy adults</a>). But sometimes it takes advantage of disruptions in our bacterial flora to cause disease. These changes are typically caused when antibiotics are used to treat an unrelated condition, killing off the protective microorganisms of our gut and allowing <em>C. diff</em> to flourish.</p>
<p>Paradoxically, more antibiotics are typically used in an attempt to kill off the <em>C. diff</em> as well. However, this can create the same problem again, leading to a <a href="http://www.ncbi.nlm.nih.gov/pubmed/25714160">recurrence of the infection</a> in approximately 30% of cases. And once the infection has recurred once, it recurs again in 60% of cases. This has led doctors to consider many alternative strategies.</p>
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<p>Giving patients bacteria thought to promote a healthy digestive system (probiotics) has been tried as a way of replacing the normal gut flora killed by antibiotics, but with <a href="http://www.ncbi.nlm.nih.gov/pubmed/25922397">little evidence</a> of success.</p>
<p>More recently, <a href="http://www.ncbi.nlm.nih.gov/pubmed/23967542">trials have begun</a> with the more controversial “faecal transplants”. Both selected bacteria from the faeces of a healthy donor and entire samples faecal matter have been implanted in a patient’s colon to test the idea. There is a growing <a href="http://www.ncbi.nlm.nih.gov/pubmed/23967542">body of evidence</a> to suggest this can provide both resolution and protection from recurrence. </p>
<p>Researchers from Loyola University Health System in Illinois have now <a href="http://jama.jamanetwork.com/article.aspx?articleid=2281703">published a trial</a> of a technique that could be described as a more refined and specific version of probiotic treatment or faecal transplant. Rather than replacing the entire gut-flora of an individual, the researchers introduced a different, harmless strain of <em>C. diff</em> that doesn’t produce any toxins.</p>
<p>Having already conducted an initial trial, the researchers expected that the non-toxic bacteria would outcompete the toxic strain and prevent the progression and recurrence of infection. The latest trial demonstrated the safety of the treatment and presented further evidence for its efficacy. The most effective dose of bacteria reduced the rate of recurrence to 5%, compared to 30% in a placebo group.</p>
<p>This is an extremely encouraging result. The next stage in the translation of this into the clinic is a phase III trial which will determine the efficacy and safety over many thousands of diverse patients. If successful this could lead to an incredible, cost-effective and widely applicable treatment. Further work is needed to understand why and how this non-toxic strain outcompetes the toxic strains in the gut.</p>
<p>There is a cautionary note, however. <em>C. diff</em> <a href="http://www.ncbi.nlm.nih.gov/pubmed/24131955">has been shown</a> to transfer its DNA (containing the toxin genes) from toxic strains to non-toxic strains in the laboratory. If the non-toxin strain is inherently more fit in the human gut than the toxic ones, and if it could readily acquire the toxin genes and become a fitter toxic strain, we may head straight back to square one. This would add yet another, even more dangerous superbug to the ever-growing list.</p><img src="https://counter.theconversation.com/content/41391/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Adam Roberts has received funding from the European Community’s
Seventh Framework Programme and the Medical Research Council. This article represents the author's own opinions not those of any organisation or funding body.</span></em></p><p class="fine-print"><em><span>Ruth Massey 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>
New research shows the best way to treat hospital infections caused by C. difficile may be with more of the bacteria.
Ruth Massey, Senior lecturer, department of biology & biochemistry, University of Bath
Adam Roberts, Senior lecturer, UCL
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/39790
2015-04-08T20:06:24Z
2015-04-08T20:06:24Z
Golden staph: the deadly bug that wreaks havoc in hospitals
<figure><img src="https://images.theconversation.com/files/77283/original/image-20150408-26496-157nml2.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Staph aureus bloodstream infection has a 12-month death rate of between 20 and 35%.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-265697000/stock-photo-close-up-a-hand-of-an-old-woman-patient-in-hospital-with-saline-intravenous.html?src=H98rKKx8knVfVLK3fpuViw-2-39">Joe Techapanupreeda/Shutterstock</a></span></figcaption></figure><p>Take this quick medical pop quiz: which of the following conditions would you prefer to have during your next stay in hospital? A. <a href="http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Staphylococcus_aureus_golden_staph">Staphylococcus aureus</a> (golden staph) bloodstream infection; or B. a heart attack?</p>
<p>I am guessing most non-medical readers voted for the Staph option and, if my experience is anything to go by, the majority of medical readers will have also made a microbial choice. </p>
<p>The disturbing truth is that a Staph aureus bloodstream infection has a <a href="https://www.mja.com.au/journal/2006/184/8/health-care-associated-staphylococcus-aureus-bloodstream-infections-clinical">12-month death rate</a> of between 20 and 35%, compared with 3-5% for a <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1208200#t=article">heart attack</a> in hospital. Although <a href="http://www.mayoclinic.org/diseases-conditions/mrsa/basics/definition/con-20024479">antibiotic-resistant Staph aureus</a> (MRSA) infections carry a slightly higher death rate, even the drug-sensitive Staphs are among the most potent of pathogens. </p>
<p>Staph aureus lives on our skin and in our nose where it usually causes no harm. But if we are admitted to hospital and have an intravenous catheter inserted through our skin, the Staph aureus can be carried on the tip of the needle into the vein. </p>
<p>Usually our immune system mops up any stray microbes but the reason for coming to the hospital in the first place may have weakened our defences. Infections such as pneumonia, the effects of cancer and its treatment, diabetes, drugs that suppress the immune system and surgery make us more vulnerable to hospital-acquired infections. </p>
<p>Very sick patients often require long-term intravenous access through central venous catheters (which are inserted into a large vein at the chest, neck or groin). These carry a higher risk of infection than small peripheral cannulas, usually inserted in veins of the hand or arm. </p>
<p>Patients with bloodstream infections develop chills, fever, headache, muscle and back pain and may go on to develop failure of one or more organ systems. </p>
<p>The complications of Staph aureus bloodstream infections (which, going back to our quiz, include a <a href="http://www.sciencedaily.com/releases/2013/08/130820083755.htm">heart attack</a>) may take weeks or months to develop; by the time the patients who survive have been discharged from the intensive care unit, the original infection may have been forgotten. </p>
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<img alt="" src="https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/77284/original/image-20150408-26507-12lv6sz.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 national benchmark for Staph aureus bloodstream infections is two cases per 10,000 patient days.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-257946281/stock-photo-abstract-of-blurred-people-in-the-hospital.html?src=ny5mCpiAqMiud8E5gVy1dA-1-115">surasaki/Shutterstock</a></span>
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<p>Today the <a href="http://www.nhpa.gov.au/internet/nhpa/publishing.nsf">National Health Performance Authority</a> released its report on health care associated Staph aureus bloodstream infections in Australia in 2013-14. This is the third year the data has been reported nationally and the news is mildly encouraging. In 2013-14, there were 1,621 bloodstream infections caused by Staph aureus, which is 100 fewer than in 2012-13. </p>
<p>Nearly 90% of the infections occurred in the 115 major and large Australian public hospitals. To make sensible comparisons, hospitals are grouped by their size and the complexity of the patients they treat. Patients with burns, cancer, HIV and those who have undergone surgery are considered to be more vulnerable to infection. </p>
<p>For the 36 major Australian hospitals with more vulnerable patients, the average rate of infection was 1.28 per 10,000 patient bed days, although the rate was more than three time higher in some of these hospitals than in others. At the 40 major hospitals with fewer vulnerable patients, the average rate was 0.78 per 10,000 patient days. </p>
<p>The agreed national benchmark is less than 2.0 per 10,000 patient days and only a handful of hospitals exceeded this rate.</p>
<p>While these data show that the risk of Staph aureus infection for an individual patient is low, when considered across the entire health system it reveals an important and costly problem. </p>
<p>These figures only relate to infections that have been acquired in a health-care setting. Staph aureus can also originate in people in the community who have had no contact with the health system and these infections also carry a high risk of death. </p>
<p>There isn’t much we can do to reduce community Staph aureus blood stream infections but we can influence the number of hospital-associated infections – as these data so happily show. One important reason for the reduction is the increasing compliance of health-care workers with hand hygiene. </p>
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<img alt="" src="https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=480&fit=crop&dpr=1 600w, https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=480&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=480&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=603&fit=crop&dpr=1 754w, https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=603&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/77285/original/image-20150408-26518-jogyjk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=603&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">Nurses’ hand hygiene compliance is at 85.5%.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-67964344/stock-photo-human-hands-being-washed-with-soap.html?src=ru59pR05ZctCVyus7Asi9A-1-46">topseller/Flickr</a></span>
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<p>The <a href="http://www.hha.org.au/LatestNationalData.aspx">most recent data</a> from Hand Hygiene Australia show that average compliance in Australian hospitals is now 81.9% across the <a href="http://www.hha.org.au/home/5-moments-for-hand-hygiene.aspx">five “moments” of hand hygiene</a>. Even my recalcitrant doctor colleagues have lifted their game – from an average of 59.6% in 2011, they have now reached 70.2% (which, I am ashamed to say, is still 15.3% behind our much cleaner nursing colleagues). </p>
<p>Other reasons for the reduction include the implementation of protocols for the insertion, maintenance and early removal of central venous catheters and, possibly, the increased preference for peripherally inserted central catheters.</p>
<p>Staph aureus is only one of many bacteria that can invade the bloodstream but, for the moment, it is the only centrally monitored and reported bacteria in Australia. <a href="http://www.niaid.nih.gov/topics/antimicrobialresistance/examples/gramnegative/Pages/default.aspx">Gram-negative bacteria</a> such as <a href="https://theconversation.com/explainer-what-is-e-coli-17503">E. coli</a> are increasingly common causes of serious infections and antibiotic resistance is arguably a more important problem in these organisms. We need to watch this medical space.</p>
<p>Nevertheless, the modest 6% reduction in the number of bloodstream infections indicates that something as banal as keeping your hands clean can make a real difference. The 100 hospitalised patients who didn’t get a Staph aureus blood stream infection last year will never know how lucky they were.</p><img src="https://counter.theconversation.com/content/39790/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Frank Bowden 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>
Which of the following conditions would you prefer to have during your next stay in hospital? A. Staphylococcus aureus (Golden Staph) bloodstream infection; or B. a heart attack?
Frank Bowden, Professor at ANU Medical School; Senior Staff Specialist Infectious Diseases, ACT Health
Licensed as Creative Commons – attribution, no derivatives.
tag:theconversation.com,2011:article/17847
2013-09-05T20:31:42Z
2013-09-05T20:31:42Z
Genomic analysis could help win the fight against superbugs
<figure><img src="https://images.theconversation.com/files/30730/original/sbs2ksz4-1378345350.jpg?ixlib=rb-1.1.0&rect=0%2C1%2C1000%2C666&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Whole genome sequencing can help identify the source of the antibiotic resistance.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Some recent headlines from Australian newspapers: <a href="http://www.smh.com.au/nsw/nsw-hospitals-worst-place-for-golden-staph-20130522-2k1b0.html">NSW hospitals worst place for Golden Staph</a>; <a href="http://www.theaustralian.com.au/news/features/the-killer-in-our-midst/story-e6frg8h6-1225697945497">CA-MRSA - the killer in our midst</a>; <a href="http://www.theaustralian.com.au/news/health-science/superbug-onslaught/story-e6frg8y6-1226562959794">Superbug onslaught</a>. </p>
<p>By now, most people are aware that antibiotic-resistant bacteria are a serious problem, as the above headlines demonstrate. The government is aware of the issue as well. </p>
<p>Two reports in the past month — one from the <a href="http://www.chiefscientist.gov.au/2013/07/antibiotic-resistance-a-serious-threat/">Office of the Chief Scientist</a> and the other from the <a href="http://www.safetyandquality.gov.au/publications/australian-one-health-antimicrobial-resistance-colloquium-background-paper/">Antimicrobial Resistance Standing Committee</a> – have called for action on antibiotic resistance in Australia.</p>
<p>Both recognised that we need co-ordinated, nationwide surveillance of antibiotic-resistant infections to avoid the nightmare of untreatable infections in hospitals. </p>
<p>A good place to start would be to invest in DNA-sequencing technology, supercomputers, and training more people in bioinformatics, a discipline that uses computers to extract meaningful information from genomic data.</p>
<p>Why? Because if we want to monitor where resistance comes from and how it spreads, genome analysis technology is a big part of the answer. Here’s an example of how it works.</p>
<h2>Genomics in action</h2>
<p>Vancomycin-resistant Enterococcus faecium (VRE) is overtaking golden Staph as the leading cause of antibiotic-resistant bloodstream infections in some Australian hospitals. </p>
<p>Until recently, it was assumed that clusters of VRE cases in hospitals were caused by resistant bacteria spreading from one patient to another, so hospitals have been trying to stop the spread of the bug by isolating infected patients at great expense.</p>
<p>A <a href="http://mbio.asm.org/content/4/4/e00412-13.long">recent study</a> at the Austin Hospital in Melbourne employed whole genome sequencing to investigate, in the finest forensic detail possible, the relationship between VRE from different patients. The results were a surprise - the bacteria differed substantially, too much to be the result of spreading within the hospital.</p>
<p>Instead, the study suggests that some patients who develop VRE infections in hospital probably had the bacteria, or a precursor, inside them when they arrived there, as opposed to picking up bugs from other patients.</p>
<p>So, isolating infected patients may not always help. Rather, we could prevent VRE infections by checking new patients to see if they are carrying the bug in their gut. And if they have VRE, and go on to develop an infection in hospital, doctors will know not to waste time with the wrong antibiotics.</p>
<p>Of course, hand hygiene and clean hospitals remain critical for stopping the spread of infections between patients.</p>
<h2>Resistance can develop during antibiotic treatment</h2>
<p>Every time a bacterium meets a drug, there is a risk that it will develop resistance. When antibiotics are used unnecessarily - to treat viral infections or bacterial infections where they have a minimal effect - they increase the risk of drug-resistant bacteria emerging. </p>
<p>For example, if you take antibiotics for a cough that’s caused by a viral respiratory infection, it won’t make you better, but it could prompt your friendly gut bacteria to develop antibiotic resistance. You probably won’t notice this because those bugs are living happily in your stomach and doing you no harm. </p>
<p>But if you then have an accident, or become sick and require surgery, those bugs could get into your bloodstream and cause serious systemic infections, or septicaemia, that is very hard to treat.</p>
<p>So, careful and controlled use of antibiotics, or “antibiotic stewardship”, is important to prevent new resistant bugs from developing.</p>
<p>Once a bacterium becomes resistant, it can spread to other people and cause more resistant infections. This is a serious problem in hospitals, where resistance develops in a patient receiving antibiotics, creating a superbug that can spread to other patients.</p>
<p>Worse, bacteria can also share their resistance by transferring bits of DNA between cells. So when one bug learns a new trick, it can quickly teach others. We need to understand this much better so that we can prevent or manage it. But the only way we can detect this happening is through DNA surveillance of bacteria.</p>
<p>This is why DNA sequencing of bacteria has become the new gold standard for tracking the emergence and spread of resistance.</p>
<h2>Critical questions that genomics can help answer</h2>
<p>Genomics can help us identify the source of the infection and how the resistance develops. </p>
<p>Much like forensics can link a suspect to a crime, DNA tracking can link a suspected source (say, a dirty sink) to a patient’s infection. This allows us to monitor the spread of resistant bacteria between hospitals and between states, as well as the introduction of new resistant bugs from overseas. </p>
<p>This information can be important for deciding when to isolate patients or introduce quarantine measures.</p>
<p>We also need to know how often resistance develops during treatment, and how often resistance spreads between patients. </p>
<p>If the problem is mainly one of spread, we need to concentrate on hand hygiene, isolating affected patients and other methods, to try to limit spread in hospitals. But if most resistance arises during treatment, we need to change our antibiotic prescribing habits to avoid this.</p>
<p>These questions are best addressed by whole genome sequencing. The technology is available, and we have the expertise in Australia to implement it for surveillance and infection control. </p>
<p>All it needs is an investment of resources. And as both recent reports have pointed out - like many reports over the past 15 years - action is needed now.</p>
<p><em>Kathryn Holt is the winner of a 2013 L'Oréal For Women in Science Fellowship.</em></p><img src="https://counter.theconversation.com/content/17847/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kathryn Holt receives funding from the National Health and Medical Research Council of Australia.</span></em></p>
Some recent headlines from Australian newspapers: NSW hospitals worst place for Golden Staph; CA-MRSA - the killer in our midst; Superbug onslaught. By now, most people are aware that antibiotic-resistant…
Kathryn Holt, NHMRC Research Fellow, The University of Melbourne
Licensed as Creative Commons – attribution, no derivatives.