tag:theconversation.com,2011:/id/topics/superbugs-vs-antibiotics-4364/articlesSuperbugs vs Antibiotics – The Conversation2024-01-05T14:54:09Ztag:theconversation.com,2011:article/2205642024-01-05T14:54:09Z2024-01-05T14:54:09ZNew antibiotic zosurabalpin shows promise against drug-resistant bacteria – an expert explains how it works<figure><img src="https://images.theconversation.com/files/567989/original/file-20240105-24-a6i28q.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5120%2C2880&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Carbapenem-resistant Acinetobacter baumannii is classified as a priority 1 critical pathogen by the World Health Organization</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-science-laboratory-portrait-beautiful-black-1922200124">Gorodenkoff/Shutterstock</a></span></figcaption></figure><p>Researchers have <a href="https://www.nature.com/articles/s41586-023-06799-7">identified</a> an entirely new class of antibiotic that can kill bacteria that are resistant to most current drugs. </p>
<p>Zosurabalpin is highly effective against the bacterium carbapenem-resistant <em>Acinetobacter baumannii</em> (Crab), which is <a href="https://www.who.int/news/item/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed">classified</a> as a “priority 1” pathogen by the World Health Organization due to its growing presence in hospitals.</p>
<p>Crab <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137960/">can kill</a> up to 60% of people infected with it. It commonly causes infections of the urinary tract, respiratory tract and blood stream, potentially leading to sepsis. It is responsible for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913636/">around 20%</a> of infections in places like hospitals, care homes or other similar healthcare settings.</p>
<p>Antibiotics commonly work by crossing the cell wall that surrounds infectious bacteria to reach the vital machinery inside. Once inside the cell, antibiotics block that machinery in such a way as to either stop the bacteria from growing or to cause cell death. </p>
<p>Crab is a clinical challenge as it has a double-layered cell wall, a feature that microbiologists describe as “<a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/gram-negative-bacteria">gram negative</a>”. This means that antibiotics need to cross both layers to reach the vital machinery inside the bacteria to kill them and treat the infection. </p>
<p>An exception to this rule is penicillin-based antibiotics, where the target is in the cell wall itself. These antibiotics, known as <a href="https://www.bmj.com/content/344/bmj.e3236">carbapenems</a>, were derived from penicillin some 48 years after it was first discovered and still work in the same way. However, they have undergone clever chemical modification to prevent bacteria successfully evolving to resist them. This makes them a vital part of treating infections like those caused by <em>Acinetobacter baumannii</em>. </p>
<p>But Crab, the superbug version of this infection, has developed the ability to break down carbapenems, giving it an evolutionary upper hand, which has led to its rise to supremacy in hospitals. </p>
<h2>Zosurabalpin</h2>
<p>This new class of antibiotic, zosurabalpin, is shown to be highly effective against Crab both in the laboratory and in infected animals. Researchers tested zosurabalpin against more than 100 Crab samples from patients suffering from the infection. The research team, <a href="https://www.nature.com/articles/s41586-023-06799-7">found</a> that zosurabalpin was able to kill all of these bacterial strains. It could also kill the bacteria in the bloodstream of mice infected with Crab, preventing them from developing sepsis. </p>
<p>Crab has the ability to make a toxin called <a href="https://www.sciencedirect.com/topics/neuroscience/lipopolysaccharide">lipopolysaccharide</a> that it uses as part of its weaponry for infecting people and which it normally embeds into its outer cell wall. </p>
<p>Zosurabalpin works by blocking a molecular machine called <a href="https://www.nature.com/articles/s41586-023-06873-0">LptB2FGC</a> that transports the lipopolysaccharide toxin from the inside barrier to the outside one. This makes the toxin build up inside the bacteria, causing the Crab cells to die. Essentially, the bacteria pull the pin out of their own grenade but zosurabalpin stops them from being able to throw it. </p>
<p>This LptB2FGC mechanism is pretty unique to Crab, which has some advantages and disadvantages. The bad news is that zosurabalpin will only kill Crab infections and not those caused by other types of bacteria. This means doctors would need to accurately diagnose patients with this infection to decide if zosurabalpin would be the right drug. </p>
<p>But a major advantage is that the chance of antibiotic resistance emerging is reduced, as this resistance could only emerge from Crab and not other types of bacteria. Hopefully, this could extend the shelf life of this drug. </p>
<p>The researchers say they have already seen some mutations in the drug target, LptB2FGC. However, these only seem to reduce the effectiveness of zosurabalpin, rather than stopping it working entirely. The great news is that this is the first time an antibiotic has been reported to work in this way. It gives microbiologists a new avenue to explore ways to kill our bacterial enemies before they kill us. </p>
<figure class="align-center ">
<img alt="Close up of microscope with lab glassware." src="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/568021/original/file-20240105-25-qzeyh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<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 UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1055202018-11-13T10:57:03Z2018-11-13T10:57:03ZWhy you shouldn’t take antibiotics for colds and flu<figure><img src="https://images.theconversation.com/files/245067/original/file-20181112-83564-5ho4bz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">And don't infect everyone else in the office either.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Winter is well and truly on its way. For many, this conjures up images of log fires, mistletoe and festive feasts. But it can also mean cold, damp mornings, short hours of daylight and the dreaded cold and flu season. </p>
<p>Tickly throats, headaches, fevers and generally feeling rotten are the warning signs that many of us fear. Pressures of work and personal commitments often lead people to seek a quick fix from their GP or other healthcare professional. This usually takes the form of antibiotics. </p>
<p><a href="http://www.who.int/antimicrobial-resistance/en/">Evidence</a> suggests the use of antibiotics is on the increase, which is a cause for concern as the overuse of antibiotics has been linked to <a href="http://www.who.int/antimicrobial-resistance/en/">antimicrobial resistance</a>. This is the ability of microorganisms – such as bacteria and viruses – to evolve so that antimicrobials (antibiotics and antivirals) become less effective at killing or working against them. </p>
<p>Antibiotic resistance results in standard treatments – such as many of the commonly prescribed antibiotics – becoming ineffective. And this leaves people who need antibiotics for serious infections vulnerable. </p>
<p>This issue has been recognised as a problem on a global scale in a <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">UK government commissioned review</a>. These findings led to the National Institute of Clinical Excellence (NICE) publishing <a href="https://www.nice.org.uk/guidance/qs121">quality standards</a> to help clinicians when prescribing antibiotics to slow the rise in antimicrobial resistance. </p>
<h2>Antibiotic expectations</h2>
<p>The <a href="https://www.cochrane.org/CD012406/AIRWAYS_macrolide-antibiotics-bronchiectasis">Cochrane review</a>, on which I worked, found that many vulnerable patients have an increased risk of developing microbial resistance. This includes people with chronic respiratory illness – many of whom have “rescue packs” which include antibiotics at home. These repeat prescriptions are often issued without enough education to support their use or <a href="https://www.pcrs-uk.org/sites/pcrs-uk.org/files/UseofRescuePacksinCOPD_5_1_2018.pdf">highlight their drawbacks</a> – so unnecessary prescribing practices continue.</p>
<p>Beliefs and expectations by patients, healthcare professionals and society have been found to be the main drivers of the <a href="http://erj.ersjournals.com/content/40/1/1.long">overuse of antibiotics</a>. From a patient’s perspective, the desire to get better is often more important than any external considerations such as publicity campaigns. And for healthcare professionals, the greater good of society occurs outside the immediate consultation and is therefore <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1325265/">often overlooked</a> – <a href="https://onlinelibrary.wiley.com/doi/abs/10.1197/j.aem.2007.07.011">along with existing evidence</a>. This breeds a cycle of expectation and self-interest which serves both clinician and patient but neglects wider societal issues. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/znnp-Ivj2ek?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>It is possible, then, that much antibiotic prescribing, particularly in the flu season, is driven by these expectations – from both patients and healthcare professionals. But this is not unique to antibiotic prescribing. Our previous research found similar behaviours with oxygen therapy. Despite emerging evidence and guidelines, poor prescribing and administration of oxygen therapy persists – and it is often given routinely for <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/crj.12571">breathlessness to patients</a>. </p>
<h2>A medical priority</h2>
<p>A UK parliamentary health and social care committee <a href="https://publications.parliament.uk/pa/cm201719/cmselect/cmhealth/962/962.pdf">report on antimicrobial resistance</a> has called for the issue to be regarded as “top five policy priority” for government – stressing the need to support the pharmaceutical industry to develop new antibiotics. </p>
<p>How Brexit will affect this investment and commitment is <a href="https://www.independent.co.uk/news/business/news/brexit-uk-pharmaceutical-research-drug-investment-select-committee-review-a8087161.html">unclear</a>. But there remains an urgent need to promote responsible and appropriate prescribing through education, research, guidelines and campaigns. </p>
<p>Current UK prescribing levels are reported as double that of other countries such as <a href="https://publications.parliament.uk/pa/cm201719/cmselect/cmhealth/962/962.pdf">Sweden, Netherlands and the Baltic States</a>. This presents a challenge for primary care and hospitals who need to reduce both the number of antibiotics prescribed and the length of time that they are administered.</p>
<h2>Antibiotic efficacy</h2>
<p>A recent <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">government report</a> has called for the use of rapid <a href="https://www.ncbi.nlm.nih.gov/pubmed/28973636">diagnostic testing</a> to inform all antibiotic prescriptions. This approach should take the <a href="https://theconversation.com/theres-a-test-that-shows-doctors-if-antibiotics-will-work-or-not-so-why-isnt-it-being-used-72892">guesswork out of prescribing</a> antibiotics by testing for blood markers that signify the presence of infection. <a href="http://www.pace-study.co.uk/">Findings from a large trial</a> based in the UK are expected soon. </p>
<p>Sometimes though, the prescribing of general use antibiotics is not only expected, but cheaper and easier. So it will require a concerted effort to promote responsible prescribing and educate all healthcare professionals, patients and the public to refrain from using antibiotics. </p>
<p>So as winter approaches, rather than rushing out to your doctors at the first sign of a sniffle, try and ride it out. <a href="https://www.nhs.uk/conditions/flu/">Get lots of sleep</a>, keep <a href="https://theconversation.com/take-a-chill-pill-if-you-want-to-avoid-the-flu-this-year-53027">stress to a minimum</a> and up your fluid intake – all of which have been shown to help in the treatment and staving off of colds and flu. It’s also worth being extra vigilant with <a href="https://theconversation.com/shaking-hands-is-disgusting-heres-what-else-you-can-do-98097">hand washing</a> to help keep those germs at bay and stop them from developing into something more nasty in the first place.</p><img src="https://counter.theconversation.com/content/105520/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Carol Kelly is affiliated with ARNS (Association for Respiratory Nurse Specialists) </span></em></p>The overuse of antibiotics puts vulnerable patients and society at risk.Carol Ann Kelly, Reader Respiratory Care, Edge Hill UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/808642017-07-18T23:09:15Z2017-07-18T23:09:15ZCanada could lead the fight for life in a post-antibiotic world<figure><img src="https://images.theconversation.com/files/178530/original/file-20170717-6084-14ldnjt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Drug-resistant strains of gonorrhoea, once easily dispatched with penicillin, are spreading across the globe resulting in chronic pain and sterility</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Infectious diseases that once were tamed are roaring back, past the last line of our antibiotic defences. They threaten the lives of millions, but where is the public outcry? </p>
<p>Drug-resistant strains of gonorrhoea, once easily dispatched with penicillin, are spreading across the globe. The result: chronic pain, sterility and a <a href="http://www.who.int/mediacentre/news/releases/2017/Antibiotic-resistant-gonorrhoea/en/">call for new drugs by the World Health Organization</a>. In North America, <a href="https://www.cdc.gov/mmwr/volumes/66/wr/mm6601a7.htm?s_cid=mm6601a7_w&utm_source=Global+Health+NOW+Main+List&utm_campaign=813e656ea4-EMAIL_CAMPAIGN_2017_01_12&utm_medium=email&utm_term=0_8d0d062dbd-813e656ea4-890763">people are dying</a> from infections caused by bacteria that are resistant to all available drugs. And sepsis, a deadly syndrome triggered by untreatable bacterial infections, is causing <a href="http://www.contagionlive.com/news/sepsis-remains-significant-challenge-for-hospitals-public-health-watch-weekly-report">millions of deaths</a> and <a href="https://www.bloomberg.com/news/articles/2017-07-14/america-has-a-27-billion-sepsis-crisis">massive health-care costs</a> among the elderly and very young.</p>
<p>Where is the Canadian co-ordination, leadership and resolve to develop new antimicrobial substances? To move innovations into the marketplace?</p>
<p>This spring, we represented Canada at the Drug-Resistant Infections Conference in Brisbane, Australia — an event that featured academic, public health and pharmaceutical industry researchers from around the world. The goal of the conference was to showcase the best research and development available to battle the antibiotics crisis. We are proud to report that Canadian research is among the most innovative in the world. </p>
<p>The time is right to launch a Canadian Anti-Infectives Innovation Network. It is time to coalesce and co-ordinate Canadian academic, private sector, not-for-profit and government research to solve the antibiotics crisis. Such a network would galvanize Canadian antibiotic research and development. It could ensure that we play a role on the international stage commensurate with our ability and promise.</p>
<h2>The microbes are winning</h2>
<p>The incredible scientific advances of the last century have allowed us to live longer and better lives by preventing or treating many diseases that were once fatal. Pneumonia, blood infections and tuberculosis were once common killers. Now they are generally cured with antibiotics. Cheap and abundant antibiotics have allowed us to <a href="http://dx.doi.org/10.1016/S1473-3099(13)70318-9">cure illnesses, keep fragile pre-term babies alive, carry out safe surgeries and treat cancer</a>.</p>
<p>Those very benefits have lulled us into ignoring a frightening problem that has been looming for decades, undermining that progress and threatening to undo those advances. </p>
<p>While we were enjoying the benefits of antibiotics, the microbes were fighting back. They were finding ways around the obstacles science and medicine had placed in their way. Now the microbes are starting to <a href="http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/">win</a>. And although we have good reason to believe <a href="http://www.pewtrusts.org/en/research-and-analysis/analysis/2017/01/18/why-the-antibiotic-pipeline-is-broken-and-how-to-fix-it">new weapons</a> could beat them back again, for some reason the world is not making enough effort to preserve our fragile safety.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.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">Sepsis dates back to ancient Greece and is now a global public health challenge, resulting in millions of death every year.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>We are in this situation because of the ever-increasing number of <a href="https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf">bacteria</a> that are no longer sensitive to the antibiotics we discovered decades ago. And because most pharmaceutical companies no longer see profitability in new antibiotic drugs. The <a href="http://petrieflom.law.harvard.edu/assets/publications/Outterson_Health_Law_Workshop_paper.pdf">business case </a>is not strong for inventing drugs that patients will only need for a short time, compared to lifelong prescriptions to treat heart and blood-pressure conditions, for example. </p>
<p>But this is not a business case. This is a public health crisis.</p>
<h2>Ordinary illnesses could kill millions</h2>
<p>We are perilously close to plunging back into a time when illnesses we consider ordinary could kill tens of millions. For some deadly strains of bacteria, we are already in a post-antibiotic world. Clinicians are out of options. Once curable diseases are incurable. <a href="http://www.contagionlive.com/news/sepsis-remains-significant-challenge-for-hospitals-public-health-watch-weekly-report">Six million people already die of sepsis</a> every year for want of effective antibiotics, and the cost to the U.S. alone is <a href="https://www.bloomberg.com/news/articles/2017-07-14/america-has-a-27-billion-sepsis-crisis">$27 billion annually</a>. Highly resistant <a href="http://www.cbsnews.com/news/superbug-gene-spotted-on-us-pig-farm/">superbugs are being found on our farms</a>.</p>
<p>In September 2016, 193 members of the United Nations came together to announce that <a href="http://www.un.org/pga/71/2016/09/21/press-release-hl-meeting-on-antimicrobial-resistance/">anti-microbial resistance (AMR) is the largest threat to medicine</a>. This was reaffirmed this month in the final statement from the <a href="https://www.g20.org/gipfeldokumente/G20-leaders-declaration.pdf">G20 meeting in Hamburg</a>. Without urgent action to overcome AMR, the <a href="https://amr-review.org/">UK’s Review On Antimicrobial Resistance</a> estimates the world could witness 10 million extra deaths every year by 2050. That is an increase of total deaths by one sixth.</p>
<p>Even those who survive drug-resistant infections will need twice as much time in hospital. And that is just one expense flowing from a problem that is expected to cost the global economy <a href="https://amr-review.org/">$100 trillion by 2050</a>.</p>
<h2>Canada could lead</h2>
<p>In a context of neglect and inaction, and the misconception that antibiotic discovery is the job of the private sector, no country is ideally positioned to solve this problem alone. Canada, however, is in a position to lead if it wants to.</p>
<p>Canadian researchers have pioneered creative solutions: alternatives to antibiotics that block and inhibit resistance, innovative drug combinations that boost antibiotic activity and enhance host immunity to prevent infection.</p>
<p>Canada’s natural resources, including the Arctic and three oceans, have the potential to deliver new antimicrobial and anti-infective substances. Vaccine development for animals and humans can reduce our need for new drugs. Our innovative thinking can deliver alternatives to reduce dependency on antibiotics. </p>
<h2>Canadian Anti-Infectives Innovation Network</h2>
<p>Innovations alone won’t help. We must do more to get Canadian know-how into action immediately. Canada is a global leader in many areas of basic and applied research that can contribute to solving the problem. But we lack co-ordination, common objectives and resolve.</p>
<p>We need to develop our innovations so we can lead the world in alternatives and adjuncts to antibiotics. We need to become an essential partner in international initiatives such as CARB-X, a public-private accelerator funded by the U.K. and U.S., to move creative antibiotic discoveries into the marketplace. Ironically, two discoveries made at McMaster University are being considered by CARB-X for funding, following licensing to U.S.-based companies. Two others developed at the University of British Columbia, and originally the basis of Canadian spinoffs, are in advanced clinical trials with U.S. companies.</p>
<p>The opportunity to grow these discoveries here in Canada has been lost. So has the associated commercial, employment and skills benefits.</p>
<p>Canada is competing and leading in anti-infective innovation, but we are rapidly falling behind in our ability to capitalize on these discoveries, foster and support new research and commercialization in Canada. </p>
<p>We must act now to ensure that we not only do our share on the international stage to solve the antibiotic crisis, but also provide a made-in-Canada innovative approach. We can do so, with support and leadership, in the form of a Canadian Anti-Infectives Innovation Network that assembles leading researchers in universities, hospitals, government and the private sector.</p><img src="https://counter.theconversation.com/content/80864/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerry Wright is a Professor and Director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. He is a co-founder and owns shares in the company Symbal Therapeutics that seeks to identify new anti-infective agents and strategies to address the antibiotic crisis. He consults widely for private sector and not-for profit agencies in the antibiotics field. His laboratory receives funding from federal and provincial funding agencies and not-for-profit groups such as the Bill and Melinda Gates Foundation. His lab has received funding over the years from both large and small pharmaceutical companies working in the area of antibiotic research and discovery.</span></em></p><p class="fine-print"><em><span>Bob Hancock has been awarded 56 patents for his UBC discoveries, largely in the area of alternatives to antibiotics, and these have been assigned to his university and licensed to several companies. If these products are successful in the long run there is the possibility that he and his co-inventors could receive milestone payments or royalties.
His laboratory has been highly funded in the past by Canadian funding agencies, and his current research is funded by CIHR, NSERC, CFI, Cystic Fibrosis Canada, and Genome Canada, as well as funding from NIH and the Australian granting agency NHMRC. He believes that he has a responsibility to ensure that his inventions are developed for the good of the Canadian public, and as such he recently founded, and is a majority shareholder in, two virtual companies - ABT Innovations and Sepset Inc - that are developing new anti-infective therapeutics and sepsis diagnostics, respectively. He consults extensively with both large Pharma and small to medium-sized biotech companies.</span></em></p>Without leading edge innovations and coordination, Canadians will die from the epidemic of antibiotic resistant infections.Gerry Wright, Professor of Biochemistry and Biomedical Sciences, McMaster UniversityBob Hancock, Professor of Microbiology and Immunology, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/686572016-12-06T20:58:45Z2016-12-06T20:58:45ZFactCheck: Is Australia’s use of antibiotics in general practice 20% above the OECD average?<blockquote>
<p>A particular focus will be Australia’s high use of antibiotics in general practice, which is 20% above the OECD average. <strong>– Minister for Health and Aged Care Sussan Ley, <a href="http://www.health.gov.au/internet/ministers/publishing.nsf/Content/health-mediarel-yr2016-ley089.htm">media release</a> announcing implementation of the <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/1803C433C71415CACA257C8400121B1F/$File/amr-strategy-2015-2019.pdf">National Antimicrobial Resistance Strategy 2015-2019</a>, November 10, 2016.</strong></p>
</blockquote>
<p>As she launched the implementation plan for Australia’s <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-amr.htm">National Antimicrobial Resistance Strategy</a>, Health Minister Sussan Ley said Australia’s use of antibiotics in general practice is 20% above the OECD average. </p>
<p>Is that right?</p>
<h2>Checking the source</h2>
<p>When asked for a source to support her statement, a spokesperson for Sussan Ley said:</p>
<blockquote>
<p>This statement is based on information contained in the <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-amr.htm">National Antimicrobial Resistance Strategy, page 11.</a> This data comes from the <a href="http://www.oecd-ilibrary.org/social-issues-migration-health/health-at-a-glance-2013/prescribing-in-primary-care_health_glance-2013-44-en">OECD Health Statistics 2013</a>.</p>
</blockquote>
<h2>Does Australia have ‘high use of antibiotics in general practice’, at 20% above the OECD average?</h2>
<p>Yes, it is high; no, it is not 20% above the OECD average. </p>
<p>The data Ley quoted is out of date, and it includes antibiotic use in all human health sectors – not just general practice (that said, the lion’s share of antibiotic scripts written in Australia are written by GPs). </p>
<p>But her broader message is correct: it is true that Australia’s antibiotic use is high and it is well above the OECD average. This is dangerous because overuse of antibiotics can lead to antimicrobial resistance, which is where antibiotics that once worked effectively no longer do.</p>
<p>The minister sourced the figure of 20% to the <a href="http://www.oecd-ilibrary.org/social-issues-migration-health/health-at-a-glance-2013/prescribing-in-primary-care_health_glance-2013-44-en">2013 OECD Health at a Glance</a> report. Using data from 2010 or the nearest year, that report found Australia’s antibiotic use to be 17.5% above the OECD average. Ley rounded that up to 20%, which is fair enough.</p>
<p>But that figure is out of date. The most recent OECD Health at a Glance report, <a href="http://www.oecd.org/els/health-systems/health-at-a-glance-19991312.htm">published in 2015</a>, shows Australia’s antibiotic use has fallen slightly since 2013. It’s now 10% higher than the OECD average. (An improvement, but still dangerously high.)</p>
<p>And the figures in both the 2013 and 2015 OECD reports include antibiotics prescribed by all health practitioners – including dentists and optometrists, for example – not just GPs. </p>
<h2>‘Defined daily doses’: findings from 2015 vs 2013</h2>
<p>There is an internationally agreed measure for comparing the use of medicines: “defined daily doses per 1,000 people per day”. Defined daily doses are <a href="http://www.whocc.no/">set and published</a> by the World Health Organisation. The OECD used this method in its reports. </p>
<p>The 2015 OECD report found that, using data from 2013 or the nearest year, 22.8 defined daily doses of antibiotics were prescribed per 1,000 people in Australia every day. The OECD average is 20.7 defined daily doses per 1,000 people every day. That makes Australia’s prescription rate 10% higher than the OECD average. (Remember, this includes antibiotics prescribed by all health practitioners, not just GPs.) </p>
<p>The chart below is from the 2015 OECD report.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=265&fit=crop&dpr=1 600w, https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=265&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=265&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=334&fit=crop&dpr=1 754w, https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=334&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/146886/original/image-20161122-24547-ul8heu.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=334&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Overall volume of antibiotics prescribed, 2013 (or nearest year). Data refer to all sectors (not only primary care).</span>
<span class="attribution"><a class="source" href="http://www.oecd-ilibrary.org/docserver/download/8115071e.pdf?expires=1479769805&id=id&accname=guest&checksum=19FF31289B832A45D0299E175CF0C652">OECD 2015 Health at a Glance report.</a></span>
</figcaption>
</figure>
<p>In the OECD chart above you will see the term “2nd line” in fine print (at the top). This refers to classes of antibiotics that medical experts say should be used conservatively to reduce the chance of germs developing resistance to them. These classes of antibiotics are called “quinolones” and “cephalosporins”. But Australia did not report the data for first and second line antibiotics separately, which is why Australia’s column in the first chart is all one colour.</p>
<p>The chart below shows Australia vs other OECD countries from the 2013 OECD report.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=329&fit=crop&dpr=1 600w, https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=329&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=329&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=413&fit=crop&dpr=1 754w, https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=413&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/146884/original/image-20161122-24533-1iuxpot.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=413&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Overall volume of antibiotics prescribed, 2010 (or nearest year). Data refer to all sectors (not only primary care).</span>
<span class="attribution"><a class="source" href="http://www.oecd-ilibrary.org/docserver/download/8113161ec044.pdf?expires=1479775366&id=id&accname=guest&checksum=69C541FABEE7C649DEE1EFB2C7CE6570">OECD, Health at a Glance report 2013.</a></span>
</figcaption>
</figure>
<p>Experts often consider the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900872/">benchmark</a> <a href="https://www.ncbi.nlm.nih.gov/pubmed/18545950">countries</a> to be those in <a href="https://www.wired.com/2010/09/antibiotic-resistance-scandinavia-gets-it/">Scandinavia</a> and the Netherlands. Australian health practitioners prescribe antibiotics at a rate 25% higher than those in <a href="http://www.oecd.org/els/health-systems/health-at-a-glance-19991312.htm">Finland</a>, and 111% higher than the <a href="http://www.oecd.org/els/health-systems/health-at-a-glance-19991312.htm">Netherlands</a>.</p>
<h2>Limitations of the OECD data</h2>
<p>There are a number of drawbacks to using the “defined daily doses” measure for comparing antibiotic use.</p>
<p>The defined daily dose applies only to adults, yet there are quite high rates of antibiotics scripts written for children.</p>
<p>The measure also fails to account for variation in standard doses in different countries. This can result in a different value for the statistic, even when the same proportion of the population took the same number of courses of antibiotics in a year.</p>
<p>Australia now has a national surveillance system for <a href="https://en.wikipedia.org/wiki/Antimicrobial">antimicrobial</a> use and resistance, and its <a href="https://www.safetyandquality.gov.au/publications/aura-2016-first-australian-report-on-antimicroibal-use-and-resistance-in-human-health/">first report</a> was released in June. The report contains a more detailed look at antibiotic use in the Australian community, using 2014 data from the Pharmaceutical Benefits Scheme. </p>
<p>Apart from counting the “defined daily doses” there’s another way to assess antibiotic use: by counting prescription numbers per head of population. </p>
<p>In 2014, there were more than 30 million scripts dispensed for systemic and topical antibiotics in Australia. It was found that at least 45% of Australians took at least one course of antibiotics during that year.</p>
<p>Unfortunately, only a few countries report their primary care antibiotic prescription numbers per head of population. These are shown in the chart below, taken from the report.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=803&fit=crop&dpr=1 600w, https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=803&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=803&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1009&fit=crop&dpr=1 754w, https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1009&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/147141/original/image-20161123-19692-inipmo.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1009&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Comparison of community antimicrobial use in Australia and other countries (prescriptions dispensed per 1000 inhabitants).</span>
<span class="attribution"><a class="source" href="https://www.safetyandquality.gov.au/publications/aura-2016-first-australian-report-on-antimicroibal-use-and-resistance-in-human-health/">AURA 2016 – First Australian report on antimicrobial use and resistance in human health, using data from Pharmaceutical Benefits Scheme (Australia); CIPARS (Canada); ESPAUR (England); SAPG (Scotland); SWEDRES (Sweden); NARMS (United States)</a></span>
</figcaption>
</figure>
<p>Overall, the point of the minister’s quote is clear: Australia’s antibiotic use in the community is unnecessarily high. </p>
<p>Evidence from Australia’s <a href="http://www.nps.org.au/medicines/infections-and-infestations/antibiotics/for-individuals/what-is-antibiotic-resistance">NPS MedicineWise</a>, presented in the <a href="https://www.safetyandquality.gov.au/publications/aura-2016-first-australian-report-on-antimicroibal-use-and-resistance-in-human-health/">AURA report</a>, makes it clear that antibiotics are often prescribed for infections when they’re not needed, particularly with respiratory viral infections like cold and flu. </p>
<h2>Verdict</h2>
<p>The data Sussan Ley quoted is a bit out of date – to be accurate, the statement should have said 10% above the OECD average, not 20% – and it refers to antibiotic use in all sectors, not just prescriptions by GPs. </p>
<p>But her broader message about Australia’s antibiotic use still being high compared to the OECD average is correct – and it’s an important point to make. Overuse of antibiotics is dangerous, as it can lead to situations where antibiotics that once worked effectively no longer do. <strong>– John Turnidge</strong></p>
<hr>
<h2>Review</h2>
<p>This analysis of Sussan Ley’s comments is accurate. I would further note that:</p>
<p>1) Government initiatives are helping to reduce antibiotic usage in other countries. For example, England just <a href="https://www.gov.uk/government/news/use-of-antibiotics-decreases-across-all-healthcare-settings-for-the-first-time">announced</a> its first decrease in usage.</p>
<p>2) While this FactCheck focuses on antibiotic usage in humans, usage in animals is much less clear, often poorly documented, and also contributes to the increase in antimicrobial resistance. In the United States, <a href="https://amr-review.org/sites/default/files/Antimicrobials%20in%20agriculture%20and%20the%20environment%20-%20Reducing%20unnecessary%20use%20and%20waste.pdf">70% of antibiotics are consumed by animals</a>.</p>
<p>Australia appears to have significantly lower antibiotic use in animals than other countries, as indicated in Australia’s first national antimicrobial resistance <a href="http://health.gov.au/internet/main/publishing.nsf/Content/1803C433C71415CACA257C8400121B1F/$File/amr-strategy-2015-2019.pdf">strategy</a>. <strong>– Mark Blaskovich.</strong></p>
<hr>
<p><div class="callout"> Have you ever seen a “fact” worth checking? The Conversation’s FactCheck asks academic experts to test claims and see how true they are. We then ask a second academic to review an anonymous copy of the article. You can request a check at checkit@theconversation.edu.au. Please include the statement you would like us to check, the date it was made, and a link if possible.</div></p><img src="https://counter.theconversation.com/content/68657/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Turnidge is a member of the Australian Society of Antimicrobials, the Australian Society of Infectious Diseases, and the Australian Society for Microbiology, which have all been active in the public debate about antibiotic resistance in Australia. He sits on the Australian Government's Australian Scientific Technical Advisory Group on antimicrobial resistance on behalf of the Commission noted above. Any opinion expressed is entirely his own.</span></em></p><p class="fine-print"><em><span>Mark Blaskovich is affiliated with The Community for Open Antimicrobial Drug Discovery. He receives funding from theNHMRC, NIH and Wellcome Trust grants, and is an inventor on several patent applications related to antibiotics. </span></em></p>Health minister Sussan Ley said Australia’s use of antibiotics in general practice is 20% above the OECD average. Is that right?John Turnidge, Affiliate Professor of Molecular and Biomedical Science, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/538552016-03-21T10:12:46Z2016-03-21T10:12:46ZFighting 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 BoulderLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/440112015-10-14T19:32:28Z2015-10-14T19:32:28ZAntibiotic resistance? Sorry, not my problem<figure><img src="https://images.theconversation.com/files/95663/original/image-20150922-16698-1qijhl1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Doctors and patients are aware of the problem – they just don't see themselves as responsible for it.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-214579408/stock-photo-young-woman-taking-bunch-of-pills.html?src=Z0SnhCB3fj-sFDKBmGMN2Q-2-112">www.shutterstock.com</a></span></figcaption></figure><p><a href="http://www.theage.com.au/victoria/deadly-superbug-found-spreading-in-victorian-hospitals-20150616-ghp9x2.html">Superbugs</a>. <a href="http://www.bbc.com/news/uk-england-34076155">MRSA</a>. <a href="http://www.news.com.au/entertainment/celebrity-life/superbug-closes-ward-at-hospital-where-duchess-of-cambridge-due-to-give-birth/story-fnisprwn-1227321535404">Hospital ward closures</a>. Ten million people <a href="http://www.bbc.com/news/health-30416844">predicted to die</a>. No new <a href="http://www.smh.com.au/national/facing-a-postantibiotic-world-20140911-10exu5.html">antibiotics</a>. If you’ve read headlines such as these, chances are they’ll come to mind when thinking about antibiotic resistance. The problem seems distant and removed from anything happening in everyday life. </p>
<p>But antibiotic resistance affects everyday life: any time an antibiotic is used, the risk of developing resistance <a href="http://www.bmj.com/content/340/bmj.c2096">increases</a>. This resistance can spread to family and other members of the community, creating a pool of <a href="http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf">resistant bacteria</a>. These resistant bacteria become problematic when an infection occurs and antibiotics that would have treated the infection are no longer effective. </p>
<p>A study we published today in the <a href="http://jac.oxfordjournals.org/content/early/2015/10/10/jac.dkv310.full.pdf+html?sid=80714bcc-45e4-4f2f-8745-54cf9251d200">Journal of Antimicrobial Chemotherapy</a> investigated perceptions about antibiotic resistance. We looked at results from 54 studies involving a total of 55,225 people who answered questionnaires or took part in interviews. </p>
<p>The data showed that on average, across the studies, 70% of people had heard of antibiotic resistance but most did not understand it: 88% of those surveyed thought the body became resistant to the antibiotics, rather than bacteria becoming resistant to the antibiotics. </p>
<p>But gaps in knowledge do not appear to be the main issue. More than 70% of people knew that using too many or unnecessary antibiotics caused antibiotic resistance. </p>
<p>The problem was they did not think they used too many or that their antibiotic use was unnecessary. In fact, they typically thought that other people were the issue – doctors prescribing too many, other people using them unnecessarily and governments not tackling the issue. </p>
<p>It is not only the public that feel this way. Another <a href="http://jac.oxfordjournals.org/content/70/9/2465">review of studies</a> we recently completed included 11,593 health professionals from 57 studies. Most (90%) of those surveyed thought using too many antibiotics caused resistance, but less than 70% believed it was a problem for their clinical practice.</p>
<p>Around half said antibiotic resistance influenced whether they prescribed an antibiotic. </p>
<p>Some also said they did not see antibiotic resistance as a priority when faced with treating an individual patient. They attributed responsibility to patients, other countries and health-care settings. </p>
<h2>Why do we think we’re not to blame?</h2>
<p>It’s unclear why people do not think they personally contribute to antibiotic resistance. Perhaps it is because there are so many contributors to the resistance problem – antibiotic use in humans, animals and the environment – that it is easy to <a href="http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.8.3063&rep=rep1&type=pdf&a=bi&pagenumber=1&w=100">overlook individual contributions</a> as a “drop in the ocean”. Not only that, the consequences of antibiotic resistance may seem distant and have been dehumanised, fostering the belief that “it will not happen to me”. </p>
<p>In contrast, sitting with a doctor in a one-to-one consultation is very much a personal interaction where the doctor and their patient might be more concerned about treating a specific infection than the risk of antibiotic resistance to society. This type of thinking is an example of the “<a href="http://www.sciencemag.org/content/162/3859/1243.full">tragedy of the commons</a>”, where shared resources are used for individual benefit until the point where they are used up and nobody can benefit. </p>
<p>Many people also tend to think they <a href="http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document/wtp059551.pdf">need something</a> when they are sick and doctors may feel pressure to meet their patients’ <a href="http://jac.oxfordjournals.org/content/66/10/2215">expectations of treatment</a>. Expectations are <a href="http://archinte.jamanetwork.com/article.aspx?articleid=2038981&cm_mid=4237214&cm_crmid=deb74c3e-872f-e311-8631-005056930045&cm_medium=email">often inaccurate</a> – people overestimate the benefits and underestimate the harms of treatment. Research shows that antibiotics offer little or no benefits for some common infections such as <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000247.pub3/abstract">colds</a>, <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000245.pub3/abstract">coughs</a> and <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD000023.pub4/abstract">sore throats</a>.</p>
<h2>What can be done?</h2>
<p>There is no simple answer. But there is no doubt a societal approach is needed. Governments, health professionals, veterinarians, members of the public and various industries are all working towards solutions. The <a href="http://www.who.int/drugresistance/documents/surveillancereport/en/">World Health Organisation</a> suggests that surveillance of antimicrobial resistance, regulating antibiotic use in humans and animals, infection prevention and control, and research innovations are <a href="http://apps.who.int/iris/bitstream/10665/44812/1/9789241503181_eng.pdf">all needed</a> to tackle the crisis. </p>
<p>The challenge is ongoing. But a key message to take away from our recent research is that although antibiotic resistance might feel distant, it is everyone’s problem. It is individuals who decide to use antibiotics, and it is individuals who have the power to minimise use and halt antibiotic resistance.</p><img src="https://counter.theconversation.com/content/44011/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Amanda McCullough receives funding from NHMRC.</span></em></p><p class="fine-print"><em><span>Chris Del Mar receives funding from NHMRC and royalties from books about evidence-based practice.</span></em></p><p class="fine-print"><em><span>Tammy Hoffmann receives funding from NHMRC and royalties from books about evidence-based practice.</span></em></p>Bacteria become problematic when an infection occurs and antibiotics that would have treated the infection are no longer effective.Amanda McCullough, Research Fellow at Centre for Research in Evidence-based Practice, Bond UniversityChris Del Mar, Professor of Public Health, Bond UniversityTammy Hoffmann, A/Prof Clinical Epidemiology, Bond University; NHMRC Research Fellow, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/470312015-09-03T20:07:11Z2015-09-03T20:07:11ZPoo transplants can eliminate two superbugs from the gut: mice study<figure><img src="https://images.theconversation.com/files/93725/original/image-20150903-24499-1l3aa8f.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Tests on mice have shown certain antibiotic-resistant gut bacteria can be treated with faecal transplants.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/rick-in-rio/2593063816/in/photolist-4X98wQ-7Z9hx4-mDqnf-78ipEh-mDqU8-mDru7-mDqdT-bRV9T6-upNTu-rxmEeF-4X4Qor-7T1Bc4-c9rtHW-771N9b-hJUByM-mDACW-bP2MWP-GuPj-4X4Qh6-7G3Teg-4kvY6K-9JErYa-S1iy-jeVEAe-6JC4P4-GjrsJ-mAB6nU-ch9VQ9-95GVc-jeXLpU-q9Y4w3-7Lj54S-jbsP-8gp6z9-arKLTr-9JDC6p-6jigU-bELyzb-9JGNUS-q4DbQa-jeZTTu-4vqjC-FeoN5-9Z1rbm-5LtYMu-ccTeCS-5zWSMf-4s6q3J-9JDCbx-jeXKGm/">Rick Eh/flickr</a></span></figcaption></figure><p>Two of the most common antibiotic-resistant bacteria circulating in hospitals can be wiped out by transplanting faeces from a healthy animal into the gut of an infected one, a study on mice has found.</p>
<p>The study, published today in the journal <a href="http://www.plospathogens.org/static/pagenotfound.action">PLOS Pathogens</a> examined two antibiotic resistant bugs: vancomycin-resistant <em>Enterococcus faecium</em> (VRE) and multi-drug resistant <em>Klebsiella pneumonia</em>.</p>
<p>A research team led by Eric Pamer, Chief of Infectious Diseases at Memorial Sloan-Kettering Cancer Centre in New York found that the bacteria can share the same location in the gut, but that “transplantation of a diverse faecal microbiota eliminates both VRE and <em>K. pneumoniae</em> from the gut.”</p>
<p>Mark Morrison, Chair of Microbial Biology and Metagenomics at the University of Queensland said the study revealed some new insights into how these bacteria colonise the gastrointestinal tract.</p>
<p>“Using a dose of other gut microbes through faecal transplantation appears to effectively displace these antibiotic resistant microbes, which warrants further investigation,” said Professor Morrison, who was not involved in the study.</p>
<p>Previous studies have found that the gut’s protective mucus layer that normally guards against microbes can thin out when gut microbiota are not well balanced.</p>
<p>Morrison said more work was needed before the findings could be applied to humans infected with these bacteria.</p>
<p>“In addition to the potential of faecal transplants, we need to ensure the prudent and effective use of existing antibiotics, and better monitor and detect these bugs. We must find new solutions to inhibit existing superbugs and develop strategies that minimise, or even eliminate, the potential for development of new superbugs,” he said.</p><img src="https://counter.theconversation.com/content/47031/count.gif" alt="The Conversation" width="1" height="1" />
Two of the most common antibiotic-resistant bacteria circulating in hospitals can be wiped out by transplanting faeces from a healthy animal into the gut of an infected one, a study on mice has found.Eliza Berlage, EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/450742015-07-24T04:38:17Z2015-07-24T04:38:17ZAntibiotic resistance doesn’t just make bacteria harder to kill – it can actually make them stronger<figure><img src="https://images.theconversation.com/files/89390/original/image-20150722-1418-1fimw50.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pseudomonas aeruginosa bacteria</span> <span class="attribution"><span class="source">CDC/ Janice Haney Carr</span></span></figcaption></figure><p>Antibiotics are wonderful drugs for treating bacterial infections. Unfortunately, disease-causing bacteria can become resistant to antibiotics that are meant to kill them. This is called selective pressure – the bacteria that are susceptible to the drug are killed, but the ones that withstand the antibiotic survive and proliferate. This process results in the emergence of <a href="http://www.cdc.gov/drugresistance/about.html">antibiotic-resistant strains</a>.</p>
<p>Once a bacterial strain is resistant to several different antibiotics, it has become a multi-drug-resistant (MDR) microbe. When there are virtually no antibiotics available to treat an infected patient, a microbe is said to be “pan-resistant.” These strains are becoming more and more common in hospitals and in the community at large. You might have heard of some of them: for instance, methicillin-resistant <em>Staphylococcus aureus</em> (<a href="http://www.cdc.gov/mrsa/">MRSA</a>), vancomycin-resistant <em>Enterococci</em> (<a href="http://www.cdc.gov/HAI/organisms/vre/vre.html#a1">VRE</a>) and carbapenem-resistant <em>Enterobacteriaceae</em> (<a href="http://www.cdc.gov/HAI/organisms/cre/">CRE</a>). </p>
<p>Bacteria can become drug-resistant in two ways – resistance can be natural, meaning that the genes conferring resistance are already present in the bacterial chromosome, or they can be acquired through mutation or by picking up antibiotic-resistance genes from other microbes.</p>
<p>It is now possible to use new DNA-sequencing technologies to take a closer look at how the antibiotic resistance can make some bacteria weaker or stronger. And in a <a href="http://dx.doi.org/10.1126/scitranslmed.aab1621">new study</a>, we found that – contrary to conventional wisdom around antibiotics – resistance can actually make some bacteria fitter and even more virulent.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=394&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=394&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=394&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=495&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=495&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89549/original/image-20150723-22826-1k2s6gw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=495&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">MRSA (Methicillin-resistant Staphylococcus aureus) bacteria strain is seen in a Petri dish containing agar jelly for bacterial culture in a microbiological laboratory in Berlin.</span>
<span class="attribution"><span class="source">Fabrizio Bensch/Reuters</span></span>
</figcaption>
</figure>
<h2>Is fitness always a cost of antibiotic resistance?</h2>
<p>For decades, an established dogma in the field of infectious diseases has been the so-called “fitness cost of antibiotic resistance.” We believed there was a trade-off for bacteria between antibiotic resistance and how well they could carry out their regular tasks of living.</p>
<p>The idea is that while antibiotic-resistant strains cause infections that are more difficult to treat, they are also less hardy. Either they are less able to survive within an infected host and/or they’re less virulent, causing less severe infection, with a reduced ability to be passed along to another human. </p>
<p>And we know that this picture is true for some bacteria. Both <em><a href="https://www.niaid.nih.gov/topics/tuberculosis/understanding/pages/cause.aspx">Mycobacterium tuberculosis</a></em> (which causes tuberculosis) and <em><a href="http://www.who.int/lep/microbiology/en/">Mycobacterium leprae</a></em> (which causes leprosy) can become resistant to the drug rifampicin, which is one of the main antibiotics used to treat these diseases. </p>
<p>For <em>M. tuberculosis</em> and <em>M. leprae</em>, resistance to rifampicin comes thanks to a mutation in one gene. The mutation buys the bacteria the ability to fend off antibiotics, but it interferes with their normal cell physiology and the factors that make them virulent. As we’d expect, resistance comes with a clear fitness cost in this case.</p>
<p>But what if resistance actually makes some bacteria stronger and deadlier? Our team used DNA sequencing techniques to tease apart the relationship between antibiotic resistance and fitness cost in infections in laboratory animals. It turns out that for some bacteria, drug resistance actually makes them fitter.</p>
<h2>Using ‘jumping genes’ to compare resistance and fitness</h2>
<p>We analyzed a bacterium called <em><a href="http://www.cdc.gov/hai/organisms/pseudomonas.html#a1">Pseudomonas aeruginosa</a></em>. It’s a major cause of infections in people with cystic fibrosis, as well as very ill patients in intensive care units (ICU) and people with weakened immune systems.</p>
<p><em>P. aeruginosa</em> is naturally resistant to several antibiotics and can acquire resistance to numerous others to become multi-drug-resistant or even pan-resistant.</p>
<p>To find out if there was a fitness cost from resistance, we created mutant strains of <em>P. aeruginosa</em> using “jumping genes” to insert mutations into the bacteria. Because we wanted to see what the cost of resistance was, we made two kinds of mutant strains. Some mutant strains lost their natural-resistance genes, while other mutant strains acquired resistance due to inactivation of genes that made them susceptible to antibiotics. </p>
<p>This meant that we could use DNA sequencing to determine how loss of each mutated gene affected the overall ability of <em>P. aeruginosa</em> to cause an infection in mice and the bacterium’s overall fitness.</p>
<h2>Antibiotic resistance doesn’t always come at a cost</h2>
<p>With an organism like <em>P. aeruginosa</em>, physicians often turn to a class of antibiotics called <a href="http://www.nature.com/news/antibiotic-resistance-the-last-resort-1.13426">carbapenems</a> to treat infections. Carbapenems kill <em>P. aeruginosa</em> through a channel or pore in the bacteria’s outer wall made by the protein OprD. That pore lets carbapenems in, which kills the cell. In more than <a href="http://www.slideshare.net/doctorrao/carbapenem-resistance-in-clinical-care-34157044">70% of human infections</a> with carbapenem-resistant strains of <em>P. aeruginosa,</em> the bacterium has stopped making the OprD pore – meaning the killer antibiotic now cannot get inside the cell. We created mutant strains of <em>P. aeruginosa</em> that could not produce the OprD protein, giving them an acquired resistance to carbapenems. </p>
<p>In our experiments, it turns out the fitness is not a trade-off for resistance in <em>P. aeruginosa</em>. We found that the most fit mutants were those that had become carbapenem-resistant because the OprD protein was no longer made. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=837&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=837&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=837&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1052&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1052&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89550/original/image-20150723-22836-1pj09z5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1052&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">40% of strains recovered from the mice’s GI tracts were OprD mutants.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-123985915/stock-photo-funny-little-rat-isolated-on-white.html?src=xDAjSEDOoFUbOazYLOqsxQ-2-16">Mouse via www.shutterstock.com</a></span>
</figcaption>
</figure>
<p>In mice with <em>P. aeruginosa</em> infections in their gastrointestinal tracts, the OprD mutants initially represented less than 0.1% of the strains used to establish infections. But after five days, the OprD mutants comprised more than 40% of the strains we recovered from the mice’s GI tracts. The “mutant” bacteria didn’t just spread because they were hard to kill (we did not give any antibiotics to the mice) but because they were fitter than the other bacterial strains infecting the mice.</p>
<p>We saw something similar when we used the mutant strains to give the mice bacterial pneumonia. The OprD mutants once again emerged as the predominant strains, but many of them were also resistant to another common antibiotic called fosfomycin. Like carbapenem resistance, fosfomycin resistance is also due to a single gene.</p>
<p>Overall, when bacteria acquired resistance to fosfomycin and carbapenem antibiotics, they became fitter and more virulent. This counters the more commonly accepted concept that there is a fitness cost due to antibiotic resistance.</p>
<p>In fact, we found that the mutant strains that lost their natural antibiotic resistance became less fit. So acquiring resistance made the bacterial cells stronger, while losing resistance made them weaker. </p>
<h2>What about other kinds of bacteria?</h2>
<p>To see if this effect was limited to <em>P. aerginoa</em>, we decided to look at two other bacterial species to see if antibiotic resistance made them fitter as well.</p>
<p>We looked at another multidrug and even pan-drug antibiotic resistance organism called <em><a href="http://www.cdc.gov/HAI/organisms/acinetobacter.html">Acinetobacter baumannii</a></em>, which causes many types of severe infections in the lungs, blood and skin, and a non-drug-resistant bacterium, <em><a href="http://www.cdc.gov/cholera/index.html">Vibrio cholerae</a></em>, which causes cholera. <em>V. cholera</em> also has some natural antibiotic resistance genes.</p>
<p>Along with coauthors Drs John Mekalanos and Stephen Lory at Harvard Medical School, we found that for <em>A. baumannii</em> and <em>V. cholerae</em>, the loss of antibiotic resistance was associated with loss of fitness and a weakened ability to cause infection. </p>
<p>But, when the bacteria <em>acquired</em> antibiotic resistance through a genetic mutation, they became more virulent, and had a stronger ability to cause infections in preclinical laboratory models of infections.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/89548/original/image-20150723-22811-1dw2wyn.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">Ensuring antibiotics are used properly isn’t enough. Handwashing to control the spread of bacteria is important.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-164609756/stock-photo-beautiful-nurse-washes-his-hands-before-the-procedure-surgical-handwashing.html?src=2vhde64PK9-q61odkcb5Wg-1-0">Handwashing via www.shutterstock.com</a></span>
</figcaption>
</figure>
<h2>What does this mean for strategies to combat antibiotic resistant bacteria?</h2>
<p>We do not expect these findings to be true for every kind of bacteria. But even if they apply to just some organisms, it means that resistant strains will not go away if we simply <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203003/">reduce or control antibiotic use</a>. </p>
<p>There is a general belief that if antibiotics are used only when needed, the antibiotic-susceptible strains will outcompete the less fit – but resistant – strains. But this strategy might not be enough to combat bacteria that get stronger when they become drug-resistant instead of weaker. </p>
<p>Handwashing and related measures can control the spread of resistant bacteria. But we also need vaccines and premade antibodies that can be given to people who are at risk for, or actually infected with, drug-resistant microbes.</p>
<p>That is something our research team from Harvard Medical School and Brigham and Women’s Hospital is pursuing. We are <a href="http://www.pnas.org/content/110/24/E2209.long">investigating</a> the development of a potentially very broad-spectrum vaccine along with another product, a human antibody, that could provide immunity to most drug-resistant bacteria, including tuberculosis and the feared MRSA strains, and perhaps even organisms causing diseases such as malaria.</p><img src="https://counter.theconversation.com/content/45074/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerald Pier is an inventor of intellectual properties (human monoclonal antibody to PNAG and PNAG vaccines) that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC, and Alopexx Pharmaceuticals, LLC, entities in which GBP also holds equity. As an inventor of intellectual properties, GBP also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC, and Alopexx Vaccine, LLC. GBP’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Partners Healthcare in accordance with their conflict of interest policies.. He receives funding from the NIH and Morris Animal Foundation for development of PNAG-based vaccines and therapies.</span></em></p><p class="fine-print"><em><span>David Skurnik is inventor of intellectual properties (use of human monoclonal antibody to PNAG and use of PNAG vaccines) that are licensed by Brigham and Women’s Hospital to Alopexx Vaccine, LLC, and Alopexx Pharmaceuticals, LLC. As inventor of intellectual properties, he has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx Pharmaceuticals, LLC, and Alopexx Vaccine, LLC</span></em></p>We used to think that antibiotic resistance came at a cost for bacteria, making them weaker. It turns out that for some bacteria, resistance can make them stronger and more virulent.Gerald Pier, Professor of Medicine (Microbiology and Immunobiology), Harvard UniversityDavid Skurnik, Assistant Professor of Medicine, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/433892015-06-17T06:15:47Z2015-06-17T06:15:47ZExplainer: what is KPC and should I be worried about these superbugs?<figure><img src="https://images.theconversation.com/files/85343/original/image-20150617-23259-axi2vc.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">New antibiotics are desperately needed to treat these infections. </span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-157681805/stock-photo-woman-lying-down-in-hospital-bed.html?src=mCMExOTXOnVDqrAEYkstyA-1-15">wandee007/Shutterstock</a></span></figcaption></figure><p>Superbugs are <a href="http://www.heraldsun.com.au/news/victoria/deadly-superbug-cre-kills-two-in-melbourne-spreads-across-victoria-infecting-60/story-fni0fit3-1227400507088">back</a> in the <a href="http://www.skynews.com.au/news/national/2015/06/16/superbug-found-in-vic-hospitals.html">news</a> – and <a href="http://www.theage.com.au/victoria/deadly-superbug-found-spreading-in-victorian-hospitals-20150616-ghp9x2.html">everybody</a> loves a good germ panic <a href="http://www.abc.net.au/news/2015-06-16/hospitals-warned-over-new-antibiotic-resistant-bacteria-kpc/6550398">story</a>. The bugs raising alarm are called KPC (<em>Klebsiella pneumoniae</em> carbapenemase) or CRE (carbapenem-resistant Enterobacteriaceae).</p>
<p>The <a href="https://en.wikipedia.org/wiki/Enterobacteriaceae">Enterobacteriaceae</a> (pronounced enter-oh-bact-ear-ee-ay-cee-ee) are a large family of bacteria, which largely live as a normal part of people’s healthy gut bacteria. It includes <em>E. coli</em> as well as some more nasty bugs such as <em>Salmonella</em> and <em>Shigella</em>, which cause gastroenteritis. </p>
<p>A member of the family that doesn’t get as much press is <em><a href="https://en.wikipedia.org/wiki/Klebsiella">Klebsiella</a></em>. It’s a fairly common cause of infections in hospitals, such as urinary tract infections and pneumonia. Different species also live widely in the environment.</p>
<p>The C refers to a <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1932750/">carbapenemase</a>, which is an enzyme the bacteria produces that can <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">break down</a> the class of antibiotics called carbapenems. <a href="https://en.wikipedia.org/wiki/Carbapenem">Carbapenems</a> are the hospital’s “big guns”, used for patients who are critically ill, or where there is resistance to other antibiotics. </p>
<p>The problem is that carbapenems share a common structure with penicillins and cephalosporins. Together, this family of antibiotics account for <a href="http://www.safetyandquality.gov.au/publications/antimicrobial-prescribing-practice-in-australia-results-of-the-2013-national-antimicrobial-prescribing-survey-november-2014/">the majority</a> of antibiotic use in hospital. </p>
<p>These bugs sometimes carry extra resistance genes which stop other commonly used antibiotics from working. This often leaves <a href="https://theconversation.com/back-to-the-future-breathing-new-life-into-old-antibiotics-to-fight-superbugs-1421">antibiotics</a> which we no longer commonly use (often because they have significant side-effects) as the only treatment option. There have been <a href="http://www.ncbi.nlm.nih.gov/pubmed/19527172">reports</a> of bacteria <a href="http://jmidonline.org/upload/sayi/18/JMID-00780.pdf">resistant</a> to all available antibiotics, and trials on the best way to treat these bugs are underway.</p>
<p>The first isolates of these bacteria seem to have been imported from <a href="http://www.ncbi.nlm.nih.gov/pubmed/21258100">travellers from overseas</a> or Australians returning home. But these bugs may spread between people relatively easily, especially in health-care facilities. <a href="http://www.abc.net.au/am/content/2015/s4256463.htm">Reports suggest</a> this has occurred in Victoria.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=391&fit=crop&dpr=1 600w, https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=391&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=391&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=491&fit=crop&dpr=1 754w, https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=491&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/85345/original/image-20150617-23256-1ddpwe0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=491&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The bacteria seems to have been imported from travellers.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-248584702/stock-photo-girl-in-the-airport.html?src=MsELYNi8-thH6MqDToSx4A-1-56">Capricorn Studio/Shutterstock</a></span>
</figcaption>
</figure>
<p>Although these infections may be easily transmitted, becoming sick from them is rare. As the bugs that carry the resistance are similar to normal gut bacteria, they can live there quite happily without causing you any bother. We call this being “colonised” by the bacterium. When they get into places they shouldn’t be (such as your lungs or into your blood) the bacteria can then cause infection. This is more likely in patients who are very unwell, such as people in intensive care units. </p>
<p>Most people who have tested positive for CRE are carrying the bacterium, but are not sick from it. Media reports are therefore <a href="http://www.skynews.com.au/news/national/2015/06/16/superbug-found-in-vic-hospitals.html">carefully phrased</a> with lines such as “have died with a … superbug in their systems”, which means the patient was colonised rather than infected. </p>
<p>When actual infection does occur, the outcomes are often poor. Intensive care units in Europe <a href="http://www.ncbi.nlm.nih.gov/pubmed/25017796">have reported</a> death rates up to 50%. This is generally because patients who acquire CRE are very sick before their infection, but <a href="http://www.ncbi.nlm.nih.gov/pubmed/25017796">outcomes</a> are certainly worse for very resistant infections than for more sensitive ones. </p>
<p>Resistance also <a href="http://www.ncbi.nlm.nih.gov/pubmed/16355321">increases</a> the cost of care and hospital length of stay, impacting everybody in the health-care system.</p>
<p>New antibiotics are desperately needed to treat these infections. The United States government has announced the <a href="http://www.idsociety.org/10x20/">10x20 initiative</a> – ten new antibiotics by 2020. Australian <a href="http://cooper.imb.uq.edu.au/">researchers</a> are <a href="http://www.deakin.edu.au/research/mmr/our-research/infection-and-immunity-theme">also</a> active in this <a href="http://www.uqccr.uq.edu.au/research/infection-and-immunity.aspx">area</a>. But antibiotic <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">development</a> is a slow process, so in the meantime, a holding strategy is needed.</p>
<p>There are two ways to hold the bugs back – prevent people from acquiring them in the first place, and slow the development of antibiotic resistance. </p>
<p><a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Infection control</a> is a critical, but often under-appreciated part of our hospitals. And the most important part of infection control is <a href="http://www.hha.org.au/home.aspx">hand hygiene</a>. The hands of health-care workers are critical to the transmission of bacteria between patients. Patients with resistant organisms are often kept isolated, but at least some of the benefit of this isolation comes from prompting health-care workers to clean their hands before and after patient care. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/85344/original/image-20150617-23223-zsvuax.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">The most important part of infection control is hand washing.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-206779540/stock-photo-surgeon-washing-hands-before-operation.html?src=jbLvMXccCsFAtGYiWjJ2wg-1-2">nata-lunata/Shutterstock</a></span>
</figcaption>
</figure>
<p>Australia has <a href="http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cd33_exec_summary.pdf">national guidelines</a> for infection control generally, and <a href="http://www.safetyandquality.gov.au/wp-content/uploads/2013/12/MRGN-Guide-Enterobacteriaceae-PDF-1.89MB.pdf">specific guidelines</a> for CRE. </p>
<p>The second key intervention is <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">antimicrobial stewardship</a>. Exposing bacteria to antibiotics is the way resistance comes about, and by reducing the use of antibiotics, we can delay resistance. Reducing the use of carbapenem is an important target of stewardship programs, which are now a mandatory requirement for hospitals to be <a href="http://www.achs.org.au/publications-resources/equipnational/">accredited</a>.</p>
<p>The last two years have been a time of rapid development in the fight against antimicrobial resistance. The <a href="http://www.who.int/mediacentre/news/releases/2015/antibiotic-resistance-lacking/en/">World Health Organisation</a> has increased its focus on resistance, and the Australian government has released its own <a href="http://www.health.gov.au/internet/main/publishing.nsf/Content/ohp-amr.htm">national strategy</a>.</p>
<p>Outbreaks such as this highlight the need for government, academia and industry to work together to help take these plans beyond the summits and discussion papers and into our hospitals. Understanding by and involvement of the public is also crucial. </p>
<p>Only with a united front can we hope to slow the “<a href="https://www.mja.com.au/journal/2013/198/5/gram-negative-resistance-can-we-combat-coming-new-red-plague">red tide</a>” of resistance.</p><img src="https://counter.theconversation.com/content/43389/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Trent has no financial disclosures relevant to this article, but has participated as an investigator in (industry-funded) clinical trials on new antimicrobial agents. He is a member of the Australian Society for Infectious Diseases, the Australian College of Infection Prevention and Control, and the Public Health Association of Australia. These views are his own, and not those of his employer or professional associations.</span></em></p>Superbugs are back in the news – and everybody loves a good germ panic story.Trent Yarwood, Infectious Diseases Physician, Senior Lecturer, James Cook University and, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/413912015-05-07T15:58:25Z2015-05-07T15:58:25ZThe 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>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/YEk1DrdrP4s?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<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 BathAdam Roberts, Senior lecturer, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/372332015-02-08T19:48:01Z2015-02-08T19:48:01ZThe water industry needs to join the fight against superbugs<figure><img src="https://images.theconversation.com/files/71292/original/image-20150206-28608-zny9tt.jpg?ixlib=rb-1.1.0&rect=11%2C23%2C3976%2C2604&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Superbug breeding ground? It's not just hospitals that have to battle the threat of antibiotic-resistant microbes.</span> <span class="attribution"><span class="source">Wong Wentong/Shutterstock.com</span></span></figcaption></figure><p>The fight against antibiotic-resistant bacteria – so-called “superbugs” – is a <a href="https://theconversation.com/we-need-new-antibiotics-to-beat-superbugs-but-why-are-they-so-hard-to-find-36144">huge challenge</a>, one that the World Health Organization has <a href="http://www.wired.com/2014/05/who-amr-report">described</a> as a grave global problem. </p>
<p>When superbugs hit the headlines it’s often because of hospital outbreaks, such as the outbreak of <a href="http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cd33_vre_brochure.pdf">Vancomycin Resistant Enterococcus</a> that infected <a href="http://www.theage.com.au/victoria/superbug-strikes-babies-in-hospitals-20131125-2y6ab.html">babies in Melbourne in 2013</a>. Yet the problem isn’t confined to hospitals – the wider environment can be important in the development and spread of these bugs, and people can be infected through food and water. </p>
<p>The <a href="http://www.nature.com/nature/outlook/antibiotics/index.html">problem of antibiotic resistance</a> is being exacerbated worldwide by the pollution of waste water with leftover drugs, providing breeding grounds for <a href="http://web.ebscohost.com/abstract?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=02731223&AN=91981610&h=3pduWiWh44h%2brTdHcrQ%2bl9DTLGNJUyknmgNiO1JCYXX22wEtkuInbQ5%2bUiWZKA31Vt08wq4O2ZUKTYrAZlIRrQ%3d%3d&crl=f">resistant bacteria and their genes</a>. The problem can persist for years, constantly refreshed by new discharges of both drugs and of resistant bacteria themselves, shed by people and animals.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=404&fit=crop&dpr=1 600w, https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=404&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=404&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=507&fit=crop&dpr=1 754w, https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=507&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/71275/original/image-20150206-28621-14hmish.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=507&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Vancomycin Resistant Enterococcus, which is impervious to one of the antibiotics used as a last resort by many doctors.</span>
<span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File%3AVancomycin-Resistant_Enterococcus_01.jpg">Janice Henry Carr/US Centers for Disease Control and Prevention</a></span>
</figcaption>
</figure>
<h2>Warning from history</h2>
<p>The fact that penicillin was <a href="http://pubs.acs.org/cen/coverstory/83/8325/8325penicillin.html">found in soldiers’ urine</a> in the second world war was, in hindsight, an early indication that antibiotics are present in waste water, and that drugs like this might go on to have an afterlife in streams, lakes and other waterways, clinging to sediment particles and upsetting the delicate bacterial balances in soils and aquatic ecosystems.</p>
<p>But no-one gave the issue much thought until chance intervened in 1992, when German scientists looking for herbicides in rivers, groundwater and lakes <a href="http://www.tandfonline.com/doi/abs/10.1080/03067319708031398#.VNSDw2SUckQ">stumbled across a chemical</a> they didn’t recognise – it turned out to be the cholesterol-lowering drug <a href="http://www.drugbank.ca/drugs/DB00636">clofibrate</a>, a cousin of the weedkiller <a href="http://npic.orst.edu/factsheets/2,4-DTech.pdf">2-4-D</a>. </p>
<p>No end of pharmaceutical pollution has <a href="http://pubs.acs.org/doi/abs/10.1021/es011055j">since been found</a> in the world’s water – analgesics, antibiotics, lipid regulators, antiseptics, beta-blockers, contraceptive hormones, anticonvulsants and X-ray contrast agents. Detectable levels of clofibrate alone are now found <a href="http://link.springer.com/chapter/10.1007/978-0-387-09808-1_1">throughout the North Sea</a>. </p>
<p>We now know that partially degraded drugs and ointments can be converted back into their active form through chemical reactions once you’ve said goodbye to them in the loo or shower. Many biodegrade, but others can be very persistent in their new environmental home. </p>
<p>Water treatment plants are thus the last barrier to drug residues and other synthetic chemicals being set loose into soils and waterways (meanwhile, there is no barrier at all for freely administered livestock drugs such as the antibiotics <a href="http://www.sciencedirect.com/science/article/pii/S0959652608000991">sulphasalazine and oxytetracycline</a>). </p>
<h2>Crucial treatment</h2>
<p>Treatment plants’ ability to strip out waste drugs varies enormously according to age, level of expertise and design standard. Even the best ones don’t remove all foreign chemicals. Advanced treatment processes are designed more for removing pathogens than for breaking down molecules, although chlorination and what’s known in the trade as “ozonation” do have some ability to change the chemistry of drug molecules (to exactly what is unclear). </p>
<p>As the use of recycled water increases, the quality of this water becomes more critical and good management of all sewer inputs by water companies becomes more important. Thus, pharmaceuticals are being identified as a potential risk in recycled water risk-management systems of utilities such as South East Water in Melbourne, Orange County Sanitation District in California, and Singapore’s <a href="http://www.pub.gov.sg/water/newater/Pages/default.aspx">NEWater</a> scheme. </p>
<p>This is leading to an increased awareness of the waste contributions from domestic catchments and high-concentration point sources such as hospitals.</p>
<p>It is time for the health and water industries to <a href="https://www.mja.com.au/journal/2013/199/6/after-life-drugs-responsible-care-initiative-reducing-their-environmental-impact">strike a bargain</a>. Health professionals need to be aware of the need for pharmaceuticals to be managed as organic and persistent pollutants. They can help the water treatment industry by being aware of what their activities are putting into the sewerage and waste disposal systems, in view of the limited extent to which these systems can deal with the large number of drugs that are stable. They should consider prescribing less toxic, less environmentally persistent, but equally effective drugs where possible, as well as trying to reduce overall drug use in the community.</p>
<p>Meanwhile, Australia should build on its reputation for innovation in water management by addressing this health issue. Tackling hot spots in “source control” such as hospitals and clinics could make significant inroads on the amount of waste drugs entering treatment plants. Treatment at source may be preferable to facing increased trade waste charges by utilities if they deem hospital wastewater inputs to be problematic. Water firms should discourage hospital staff from emptying half-empty syringes into wash basins (which is probably common despite being against protocols). Rubbish disposal systems that minimise medicines ending up in landfill are another must.</p>
<p>The water industry should aim to ensure that treatment plants are operating under optimal conditions and that the older ones are either replaced or upgraded. Where appropriate, the industry could also help hospitals with in-house waste treatment, and suggest ways for householders to dispose of unwanted drugs – perhaps along the lines of Orange County’s <a href="http://www.nodrugsdownthedrain.org/NoDrugs">No Drugs Down the Drain</a>“ campaign.</p>
<p>The search for new antibiotics to beat superantibiotics goes on. The discovery of one of the very few new candidate antibiotics in the past 30 years, <a href="http://www.nature.com/nature/journal/v517/n7535/full/nature14098.html">teixobactin</a>, while encouraging, is no cause for complacency.</p>
<p><em>This article was co-authored by David Smith, water quality manager for South East Water, Melbourne.</em></p><img src="https://counter.theconversation.com/content/37233/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The fight against antibiotic-resistant bacteria – so-called “superbugs” – is a huge challenge, one that the World Health Organization has described as a grave global problem. When superbugs hit the headlines…Peter Fisher, Adjunct Professor, Global, Urban and Social Studies, RMIT UniversityPeter Collignon, Professor, infectious diseases and microbiology, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/181602013-09-12T12:14:14Z2013-09-12T12:14:14ZSuperbugs move faster than governments can act<figure><img src="https://images.theconversation.com/files/31238/original/khyk2pqy-1378980083.jpg?ixlib=rb-1.1.0&rect=0%2C9%2C2112%2C1587&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Time to shelve our overuse of antibiotics.</span> <span class="attribution"><span class="source">Elsamu</span></span></figcaption></figure><p>Infections and deaths caused by superbugs are increasing every year. So the government’s five-year strategy to tackle the problem, if a little tardy, is a welcome step. </p>
<p>In January, Chief Medical Officer Sally Davies said antimicrobial resistance posed <a href="http://www.theguardian.com/society/2013/jan/23/antibiotic-resistant-diseases-apocalyptic-threat">such a catastrophic threat</a> that within 20 years we could return to a pre-antibiotic era where people die from routine infections because we have nothing to treat them with.</p>
<h2>Production stalled</h2>
<p>Many existing antibiotics are no longer effective and their production has stopped. The number of antibiotics available for use by doctors has <a href="http://www.manchester.ac.uk/escholar/uk-ac-man-scw:78144">reduced by nearly 25%</a> and in life-threatening situations where MDR organisms cause infections in the critically ill, old antibiotics (which are often toxic) are used in an attempt to save their life.</p>
<p>The development of new antibiotics is at an all-time low and many pharmaceutical companies have changed the focus of their research and development programmes to meet the treatment needs for lifestyle illnesses such as diabetes and obesity. </p>
<p>The speed and cost of developing a single antibiotic, estimated at £300-£550m, can be prohibitive. The associated scientific and regulatory challenges make <a href="http://www.telegraph.co.uk/finance/newsbysector/pharmaceuticalsandchemicals/9010738/The-battle-to-discover-new-antibiotics.html">this type of project riskier</a> than other drug-related research. </p>
<p>Totally <a href="https://theconversation.com/marine-compound-first-new-natural-antibiotic-in-decades-16433">new discoveries are rare</a> but the <a href="http://www.who.int/bulletin/volumes/89/2/11-030211/en/">potential to find new bacteria</a> to culture is there.</p>
<h2>Better late than never</h2>
<p><a href="https://www.gov.uk/government/publications/uk-5-year-antimicrobial-resistance-strategy-2013-to-2018">The government’s strategy</a> has three major aims in slowing the development and spread of antimicrobial resistance: improve knowledge and understanding; conserve and steward the effectiveness of existing treatments; and stimulate the development of new antibiotics, diagnostics and novel therapies.</p>
<p>It has promised major investment in areas including improving infection control in people and animals through better hygiene, surveillance and monitoring; improving farming practises; education and training in health-care on appropriate use and also importantly, collecting better data on resistant bugs so we can track them more effectively, find the most resistant bacteria and step in earlier.</p>
<p>In addition the strategy sets out to encourage further development of new antibiotics, rapid diagnostic methods and alternative treatment strategies and provide £4m in funding to set up a new research unit to focus on antimicrobial resistance and health-care associated infections.</p>
<p>Demand on the National Health Service is probably greater than ever before. Medical advancements are exciting and we now expect to survive conditions we’d previously have died from. However, it is the introduction of some of these advancements and the lack of understanding of the interaction with the microbial community that has helped create the problems we are now facing. </p>
<h2>Adapting fast</h2>
<p>The threat posed to our health is palpable. Common organisms that are capable of causing disease, such as <em>Staphylococcus aureus</em>, have acquired pieces of DNA (genes) that have allowed them to survive in the presence of antibiotics. These organisms have continued to acquire more genes and are now resistant to the majority of antibiotics and are known as multiply drug resistant (MDR). </p>
<p>Multiple drug resistance is also found in organisms that cause tuberculosis, and infections in the skin, chest, blood stream and gastrointestinal system to name a few.</p>
<p>Bacteria, viruses and fungi are all adapting to their environment and in hospitals and other health-care facilities where antibiotics are frequently used (sometimes inappropriately), this has occurred with alarming speed. </p>
<p>The first case of methicillin-resistant Staphylococcus aureus (MRSA) occurred a few years after the introduction of the antibiotic in 1961, but it wasn’t until the late 1980s and early 1990s that the numbers of cases rapidly increased. It is now a global problem and frequently causes health-care associated infection. </p>
<p>Although major investment has been made to minimise the spread, for example through infection control, a “wash your hands” campaign and alcohol hand gels, it’s now unlikely to disappear from hospital altogether. </p>
<p>We are now seeing this organism in the community too. Worryingly, other common organisms found in hospital areas are also becoming multiply drug resistant and are found contaminating some of the medical equipment used in critical care.</p>
<p>We must conserve the antibiotics we have left by using them effectively. And the process of developing new antimicrobials and getting them to market safely must be accelerated. We also need to further develop a rapid diagnosis of MDR infections to allow more targeted treatment rather than using antibiotics with a shot gun approach.</p>
<p>We all - doctors, patients, the public and <a href="http://www.theecologist.org/News/news_analysis/897405/overuse_of_drugs_in_animal_farming_linked_to_growing_antibioticresistance_in_humans.html">farmers and animal keepers</a> who use antibiotics - need to understand the value and importance of antibiotics and the dangers of inappropriate use. I</p>
<p>The interaction between man, microbe, environment and the drugs that we develop needs to be fully understood. The new strategy is a great step, but as resistance grows we need to move much faster and keep up the momentum. Let’s hope it isn’t a little too late.</p><img src="https://counter.theconversation.com/content/18160/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Val Edwards-Jones is a Consultant Microbiologist for Embarrassing Bodies on Channel 4. She is also Professor of Microbial Proteomics at Northwick Park Institute of Medical Research and Managing Director of EssentialMicrobiology Ltd</span></em></p>Infections and deaths caused by superbugs are increasing every year. So the government’s five-year strategy to tackle the problem, if a little tardy, is a welcome step. In January, Chief Medical Officer…Val Edwards-Jones, Professor of Medical Microbiology, Manchester Metropolitan UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/153102013-06-19T18:14:06Z2013-06-19T18:14:06ZSilver bullets kill bacteria, not werewolves or witches<figure><img src="https://images.theconversation.com/files/25850/original/7rddp79j-1371636675.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A microscopic version of this kills bacteria.</span> <span class="attribution"><span class="source">Ed Schipul</span></span></figcaption></figure><p>The use of silver in medicine is <a href="http://tse.colloidalsilverkillsviruses.com/pdf/history.pdf">as old as</a> western medicine itself. Hippocrates is known to have used it to treat ulcers and wounds, the Romans almost certainly knew of its healing properties, its use continued through the middle ages and up to the present day. In the antibiotic age, interest in silver may have waned a little. But with urgent need to fight antibiotic-resistant bacteria, there is resurgence in its uses.</p>
<p>The reason is that silver can kill bacteria selectively and, more importantly, bacteria are unable to develop resistance against it. Despite silver’s long medical history, we do not know how it operates.</p>
<p>A paper published today in the journal <a href="http://dx.doi.org/10.1126/scitranslmed.3006276">Science Translational Medicine</a> sheds some light on silver’s success against bacteria. The most important find is that silver – unlike most antibiotics – works in more than one way. This is perhaps why bacteria are not able to build resistance to silver. </p>
<p>Here is silver’s multi-pronged approach: first, silver sticks very strongly to sulfur, found in parts of proteins. These sulfur groups normally bond to each other in proteins, holding them together and keeping the protein folded up in its correct shape. But if silver interacts with sulfur then the protein cannot fold correctly, and thus it cannot do its job. Next silver interferes with how bacteria use iron. Iron is often held in the places it is needed by binding to sulfur. And since silver also interacts with sulfur it stops the iron doing so. Finally, silver causes bacteria to produce extremely toxic substances called reactive oxygen species. These go on to cause damage inside the cell, harming the DNA, proteins and even the membranes that surround cells.</p>
<p>The net result of this silver onslaught is bacteria with severely damaged defences. Most importantly the membranes and walls that surround it are leakier after the silver treatment. Once weakened, they are much more susceptible to conventional antibiotics. </p>
<p>James Collins, at Boston University, who led the research showed that with added silver, less antibiotic drug is needed to kill the bugs. A great result in itself, but it gets better. Silver also reverses antibiotic resistance of <em>E. coli</em> bacteria making them, once more, susceptible to tetracycline.</p>
<p>These experiments not only worked in a Petri dish. When silver was added to standard antibiotics such as gentamicin and vancomycin, Collins could treat <em>E. coli</em> infections in the bladder and abdomens of mice. Normally these drugs have little effect on <em>E. coli</em> infections because they are designed to attack a completely separate class of bacteria. </p>
<p>Bacteria are broadly classified into two groups called Gram-negative or Gram-positive. Gram-negatives have an extra cell membrane that protects the bacteria, which means that it is much more difficult for some antibiotics, such as gentamicin and vancomycin, to penetrate the cell. It seems that silver negates this advantage and allows even weaker drugs to do their jobs.</p>
<p>Finally, Collins showed that the mice themselves remain unharmed by silver. If he is able to repeat this work in humans, then he may actually have a “silver bullet” for antibiotic resistance.</p><img src="https://counter.theconversation.com/content/15310/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Lorch 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>The use of silver in medicine is as old as western medicine itself. Hippocrates is known to have used it to treat ulcers and wounds, the Romans almost certainly knew of its healing properties, its use…Mark Lorch, Professor of Science Communication and Chemistry, University of HullLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/138852013-05-17T05:53:10Z2013-05-17T05:53:10ZTeasing out harmful bacterial genes to reduce resistance to antibiotics<figure><img src="https://images.theconversation.com/files/264/original/AAP_superbug.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The drugs don't work. But a swifter way of identifying bacteria could reduce the need for antibiotics.</span> <span class="attribution"><span class="source">AAP</span></span></figcaption></figure><p>Researchers have taken the first step towards designing a rapid way of identifying harmful bacteria in infections, demonstrating the potential for faster patient treatment and decreased reliance on antibiotics.</p>
<p>The collaborative effort, <a href="http://mbio.asm.org/content/4/2/e00064-13.long">reported by journal mBio</a>, involved scientists from many US universities and government research institutes. Led by Christopher Grim at the US Food and Drug Administration, the group aimed to identify the disease-causing genes of <em>Aeromonas hydrophila</em> bacteria and create a “checklist” of genes that doctors could use to spot harmful members of the species in patients.</p>
<p><em>A. hydrophila</em> is found in freshwater and estuaries worldwide, usually existing harmlessly in the environment. Occasionally, however, it can infect a human through an open wound exposed to water, or by being swallowed. Open wounds infected with <em>A. hydrophila</em> can result in a potentially fatal flesh-eating disease, called “necrotising fasciitis”.</p>
<p>The researchers investigated two strains of <em>A. hydrophila</em> taken from an inflamed wound. Both strains were resilient to initial antibiotic treatment, though one was more persistent and the major cause for inflammation. </p>
<p>They sequenced the entire genetic sequence (genome) of both types of <em>A. hydrophila</em>, as well as those of several close relatives. By comparing the genetic codes they identified the genes the harmful strain had that its relatives didn’t. </p>
<p>They then used common tests to show that a selection of the identified genes improved the bacteria’s ability to cause disease. One test investigated how effectively the bacteria destroy red blood cells, which causes inflammation. When broken up, these cells release haemoglobin - the compound that gives them their colour. The colour change this causes in a culture can then be measured.</p>
<h2>The cause of resistance</h2>
<p>Traditional ways of identifying bacteria of any species involve comparing bacterial growth under different conditions. This can take days, weeks or even months. During this time, patients are generally treated with broad-spectrum antibiotics that kill many bacterial species. However, as with the harmful <em>A. hydrophila</em>, more specific antibiotics are required to kill some pathogens. </p>
<p>This means that broad-spectrum antibiotics are being used unnecessarily in efforts to treat patients. Over time, this causes an increase in antibiotic resistance as <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">bacteria evolve to defend themselves</a>.</p>
<p>Joshua Shak of Emory University, a co-author of the study, believes that genetics-based diagnoses could slow the spread of antibiotic resistance. The technology’s use in identification of bacteria could allow faster turnaround on test results. This would, if selective medicines were developed, minimise reliance on broad-spectrum antibiotics, because doctors would know earlier whether specialist treatment was needed. If fewer bacteria are exposed to antibiotics then the chances of any evolving resistance are reduced.</p>
<h2>Towards a dream</h2>
<p>Shak acknowledges, however, that the use of genomics in diagnostics is still years from becoming commonplace. So is the development of tailored medicine. He says that, while the technology for rapid sequencing exists, analysis of the data is still a relatively slow process.</p>
<p>Gary Van Domselaar, a bioinformatician at the University of Manitoba, agrees with Shak. He says, “These new technologies have placed the ability to sequence biological organisms in the hands of nearly any research laboratory. The current major hurdle no longer lies in the generation of whole genome sequences, but in their analysis.”</p>
<p>The current limitations of data analysis are seen in this study. The <em>A. hydrophila</em> genome is roughly 4.7 million characters long and within it there are over 4,000 genes. The group sequenced the isolated strains’ genomes in a matter of days, yet it took years to confirm the genes involved in causing disease.</p>
<p>Despite this, Shak hopes that, as the genomes of more bacterial species are sequenced and analysed, further analyses will become easier and faster. This is the beginning of the dream where medicines are tailored to individual patients’ needs according to the genes of the bug causing trouble.</p><img src="https://counter.theconversation.com/content/13885/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Ian Wilson 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>Researchers have taken the first step towards designing a rapid way of identifying harmful bacteria in infections, demonstrating the potential for faster patient treatment and decreased reliance on antibiotics…Ian Wilson, PhD student, University of LiverpoolLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/107242012-12-06T19:49:22Z2012-12-06T19:49:22ZNew antibiotics: what’s in the pipeline?<figure><img src="https://images.theconversation.com/files/18378/original/jfn247g3-1354754944.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">There are no magic bullets in the antibiotic pipeline that will eradicate the superbugs.</span> <span class="attribution"><span class="source">Alessandro Pinna</span></span></figcaption></figure><p>Bacteria are one of the most successful colonisers of the planet. They can be found in almost all environments we know – from the deepest oceans to acid lakes, and inside and on our bodies. And the history of medicine is the struggle to defeat them.</p>
<p>One of the reasons for the success of bacteria is their rapid growth (some divide every 20 minutes) and ability to quickly mutate and exchange their genetic code (their DNA). These factors facilitate rapid evolution, which today has led to the emergence of drug resistance in bacteria. These bacteria eventually evolve into multi-drug resistant (MDR) bacteria, or “superbugs”, that are almost impossible to control. Some bacterial infections are so difficult to eradicate that amputation is the only option available to physicians.</p>
<p>But the bad news doesn’t end there. </p>
<p>There’s a subset of bacteria called the Gram-negative bacteria. These have an extra barrier around them (an additional membrane) that can block drug entry and that makes them ever harder to kill. Even if a drug can get in, these superbugs are often able to pump the antibiotic back out of the bacteria, or deactivate it with enzymes that render the drug useless.</p>
<p>Antibiotics need to be very safe to use and have minimal or no side effects. Traditionally, most antibiotics were derived from natural products isolated from different fungi and bacteria. There have been a smaller number of antibiotics that have been derived from compounds chemically synthesised in the laboratory. </p>
<p>But discovering non-toxic, novel antibiotics from bacteria and fungi has become increasingly difficult as exhaustive searches for new sources of natural products have been going on for more than 70 years. The alternative – chemically synthesised molecules – have their own problems, as many cannot reach their biological target inside the bacteria due to the barriers mentioned above.</p>
<p>One way to control superbugs is to develop new antibiotics that kill through a different mechanism to existing drugs. But there have been only five new chemical classes of antibiotics launched since 1970 – linezolid (2000) and daptomycin (2003) for systemic infections, mupirocin (1985) and retapamulin (2007) for topical infections, and the recent approval of fidaxomicin (2012) for the treatment of gut infections caused by Clostridium difficile.</p>
<p>Before a new drug is approved, it needs to go through laboratory (pre-clinical) testing and clinical development (testing in humans). Drugs still in testing at these stages, which are not yet approved for sale, form the “antibiotic pipeline”. </p>
<p>Two major organisations, the <a href="http://www.idsociety.org">Infectious Diseases Society of America</a> (IDSA) and <a href="http://www.ecdc.europa.eu/">European Centre for Disease Prevention and Control</a> have analysed the antibiotic pipeline and concluded there are only a few potential drugs offering significant benefits over existing drugs. More alarmingly, there are very few antibiotics that are able to treat Gram-negative infections, such as NDM-1 bacteria.</p>
<p>This <a href="http://www.nature.com/ja/journal/v64/n6/full/ja201144a.html">prompted us to analyse antibiotics</a> in clinical development and those launched into the market since 2000. We found that there were an equal number of natural product-derived and chemically synthesised compounds in early clinical development. But, with the exception of just one class of antibiotic called the fluoroquinolones, natural product-derived compounds predominate in late stage clinical development. </p>
<p>There are still only a few compounds in the pipeline able to treat fluoroquinolone-resistant Gram-negative superbugs – <a href="http://tphase.com">Tetraphase’s</a> tetracyclines TP-434 and TP-2758, <a href="http://www.basilea.com">Basilea’s</a> monobactam-siderophore hybrid BAL30072 and the <a href="http://www.achaogen.com">Achaogen’s</a> aminoglycoside ACHN-490. </p>
<p>The antibiotic pipeline for the treatment of Gram-positive infections is a little brighter, and many of these compounds look likely to be able to help treat today’s Gram-positive superbugs. But it should be noted that many patients infected with these superbugs, such as MRSA, still die in hospital, especially if the bacteria is circulating the blood (septicaemia).</p>
<p>So where does this leave us?</p>
<p>The introduction of antibiotics more than 70 years ago escalated the conflict between humans and pathogens to code red. Although we seemed to be winning the war for the first 40 years, the rear guard action of superbugs in the last 20 years has left us reeling and, in some cases, defenceless. </p>
<p>It’s hard to fathom why we have accelerated the rise of the superbugs through the indiscriminate use of antibiotics in medicine and agriculture. Unfortunately, this is not a normal war with an armistice or surrender, as these pathogens will be fighting us for eternity.</p>
<p>There are no magic bullets in the antibiotic pipeline that will eradicate all superbugs. Although the discovery of new antibiotics is not a trivial task, as a society we must rise to the challenge and take action to find new and improved antibiotics, in addition to innovative ways to control these bacteria today or risk a future returned to the pre-antibiotic age.</p>
<hr>
<p><strong>This is the final article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p><img src="https://counter.theconversation.com/content/10724/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Butler receives funding from NHMRC for antibiotic and antifungal research.</span></em></p><p class="fine-print"><em><span>Matthew Cooper receives funding from the NHMRC for antibiotic research.</span></em></p>Bacteria are one of the most successful colonisers of the planet. They can be found in almost all environments we know – from the deepest oceans to acid lakes, and inside and on our bodies. And the history…Mark Butler, Senior Research Fellow at the Institute for Molecular Bioscience, The University of QueenslandMatthew Cooper, Prof. Institute for Molecular Bioscience, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/109842012-12-05T19:40:11Z2012-12-05T19:40:11ZA peek at a world with useless antibiotics and superbugs<figure><img src="https://images.theconversation.com/files/18344/original/8dj7qkcd-1354668730.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">We already know what a world without effective antibiotics would look like - just recall the pre-antibiotic era.</span> <span class="attribution"><span class="source">Lynae Zebest</span></span></figcaption></figure><p>History not only shows us our errors but also predicts our future. So, we don’t need to speculate about what a world full of superbugs and useless antibiotics would look like, we just need to recall the pre-antibiotic era (before the 1930s). </p>
<p>Our trajectory into the past is compounded by an ageing population that’s more susceptible to infections, overcrowded hospitals where infected and uninfected patients share facilities, a complacency toward basic hygiene principles and globalisation and its attendant increase in medical tourism that provides a free flight for any superbug seeking a new home.</p>
<p>In the absence of effective antibiotics, management of infected patients will be reduced to cleaning wounds and applying topical antiseptics. And removing the focus of infection, which could be a whole limb. The problem is that many of the infections we see in hospitals are actually acquired in the hospital itself and affect patients who are at their most vulnerable, having had heart surgery or other urgent procedures. </p>
<p>Exacerbating this is our reliance on intravenous tubes and catheters that measure blood pressure or deliver drugs to patients, particularly in intensive care units. These provide a veritable freeway, allowing superbugs to gain direct entry into our bodies. </p>
<p>The rise of superbugs could herald an era of deferring all non-essential surgery and caring for the sick outside of hospitals or with minimal intervention wherever possible. Perhaps quarantine hospitals and sanatoriums will be needed to separately house infected patients in the hope that good nutrition and rest will enable their immune systems to tackle the infection.</p>
<p>Technical and medical advances may provide new hope but let’s not forget the lessons of the past, which clearly demonstrated that simple hygiene has a huge impact on controlling infections. All hospitals should be able to provide patients with individual bathrooms and place a greater emphasis on physically separating patients who have resistant infections from people who are uninfected but highly susceptible. </p>
<p>We will need to prioritise cleaning of hospital areas to ensure that superbugs don’t persist in the environment. And novel immune therapies may hold some promise for the infected patient in the era of failing antibiotics. </p>
<p>Immune therapies try to boost the body’s natural defences against microbes because our immune system has evolved to eradicate infecting microorganisms. Some immune cells are dedicated to engulfing and killing invading microbes while others find and kill any resident cells that are infected with microbes.</p>
<p>Each cell in our body is equipped with a suicide program that’s activated if the cell senses that it’s infected. Some microorganisms have developed mechanisms to counter immunological onslaughts, either by switching off the suicide program or by exhausting or paralysing immune cells. <a href="http://www.ncbi.nlm.nih.gov/pubmed/21295337?dopt=Abstract">Research into the immune system</a> has provided insights into how we can enhance immunity to eradicate infections, regardless of whether the infecting organism is resistant to antibiotics. </p>
<p>The advantage of boosting immunity is, of course, that it offers a common platform to tackle many bugs. Traditionally, antibiotics only kill one type of microorganism or group of microorganisms. The advantage of immune therapies is that they can be used against many – maybe all – infections. This would also make it very difficult for microorganisms to become resistant because that would take many years of evolution. </p>
<p>Immune therapies can take the form of <a href="http://www.ncbi.nlm.nih.gov/pubmed/19396174?dopt=Abstract">administering additional immune “hormones”</a>, which are natural proteins in our bodies that facilitate immunity. By giving additional quantities of these “hormones”, we can promote the function of immune cells. Animal studies have indicated that these types of therapies hold much promise and human studies are underway. Another type of immune therapy is administering drugs that switch on the suicide program in infected cells where the program has been disabled by the infecting microbe. </p>
<p>Most importantly, we mustn’t forget the great success of vaccines, which promote immunity to prevent infection. Basically, they arm the immune system by providing it with a clear picture of the enemy, so that immune cells are at the ready. Indeed, vaccination is the most successful medical intervention of all time because it has facilitated the eradication of several viruses. We must now try to <a href="http://www.ncbi.nlm.nih.gov/pubmed/22617834">apply this success to bacteria</a>. </p>
<p>At the height of the antibiotic era, we felt secure that the microbe was conquered. Our lack of insight and complacency has made us look foolish and arrogant as microbes are retaking their position as the major cause of human suffering and death. </p>
<p>The lessons we’ve already learnt, along with pioneering research, will hopefully provide us with an advantage in combating infections so that, in the future (tempered by greater wisdom), we can feel more secure that microbes and the diseases they cause can be conquered with novel therapies and good management.</p>
<hr>
<p><strong>This is the seventh article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10984/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marc Pellegrini receives funding from NHMRC and the CASS Foundation.</span></em></p>History not only shows us our errors but also predicts our future. So, we don’t need to speculate about what a world full of superbugs and useless antibiotics would look like, we just need to recall the…Marc Pellegrini, Researcher, Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/107552012-12-05T19:39:09Z2012-12-05T19:39:09ZTrading chemistry for ecology with poo transplants<figure><img src="https://images.theconversation.com/files/18206/original/kqx3h449-1354244920.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">As simple as the procedure sounds, we don’t yet fully understand how faecal transplants work.</span> <span class="attribution"><span class="source">Image from shutterstock.com</span></span></figcaption></figure><p>Antibiotics joined our growing arsenal of weapons in the fight against disease over seventy years ago. Their target – the bacterial infections that putrefied our wounds, filled our lungs with pneumonia, and made our genitals less than appealing to our lovers. Bacteria were worthy opponents, and with antibiotics, the war against infection seemed ours to win. </p>
<p>But gradually, two facts have become abundantly evident. The first is that not all bacteria are foe. There are billions of bacteria – many of them essential to our health – that call us home. We’re each colonised by trillions of microbes forming communities that occupy every imaginable niche in our body. </p>
<p>These microbial commensals – known collectively as our microbiome – have evolved with us over millennia, and a co-dependent relationship has resulted. </p>
<p>While we provide a cosy niche and abundant supply of food to the microbes living in our intestine or on our skin, they in turn help to release nutrients from otherwise indigestible dietary fibre, synthesise essential vitamins, or produce a moisturising film to keep our skin soft and supple. </p>
<p>The second fact is that antibiotics may be thwarting our best efforts to stave off infection by messing with the delicate ecosystems that our microbial companions form. By indiscriminately annihilating microbes with antibiotics, we are taking a carpet-bombing approach where an assassination is more what we’re after. Innocent bystanders, as well as some of our closest allies, inevitably end up as casualties. </p>
<p>Unsurprisingly, some wily species of bacteria have evolved to take advantage of an ecosystem that has been thrown out of balance. The diarrhoea-causing bacterium, <a href="http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cd33_cdiff_brochure.pdf">Clostridium difficile</a>, is one such organism that flourishes in the power vacuum that results after antibiotic treatment. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=493&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=493&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=493&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=620&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=620&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18208/original/rjg4q8hq-1354246754.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=620&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Clostridium difficile.</span>
<span class="attribution"><span class="source">AJC1</span></span>
</figcaption>
</figure>
<p>A small number of people naturally harbour C. difficile in their large intestine, but most become infected in hospitals or nursing homes, the typical breeding grounds for superbugs. </p>
<p>In recent years, a highly toxic strain of C. difficile has emerged in hospitals in North America. In 2010, <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935936/">it was estimated</a> that half a million people in the US were infected with C. difficile, and up to 20,000 of those died from the infection. The C. difficile superbug is also on the move, with cases in Europe and Australia rising. </p>
<p>For an increasing number of people, even the strongest antibiotics are powerless against C. difficile. In these cases, exasperation has turned to ingenuity, with an increasing number of doctors abandoning chemical warfare in favour of an ecological approach to fighting C. difficile infection.</p>
<h2>Introducing the poo transplant</h2>
<p>The unsavoury, yet highly effective treatment that has been adopted as an alternative to antibiotics is the faecal microbiota transplant, aka the poo transplant. A poo transplant is exactly as it sounds – taking faeces from a healthy donor, and transferring it, usually via enema, to a willing recipient.</p>
<p>It’s a simple idea, really. By replacing a depleted, out-of-balance gut ecosystem with a robust and healthy one, balance is restored. C. difficile becomes out-competed by friendly bacteria and the diarrhoea ceases. Unlike blood infusions and tissue transplants, faecal transplants require no immunological typing (tests to determine donor-recipient compatibility) to prevent rejection. </p>
<p>Poo transplants are the ultimate in probiotics. Although consuming a tub of <a href="http://www.wisegeek.com/what-is-lactobacillus.htm">lactobacillus</a>-laden yoghurt is easier to swallow than the idea of a faecal enema, the principals are essentially the same. </p>
<p>There has been a resurgence of the technique, faecal transplants are not new. A Denver surgeon, Dr Ben Eiseman, and his colleagues published the first report of the procedure in 1958. And once again, doctors are discovering what Eiseman did 50 years ago – that poo transplants work. </p>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/23152734">A recent review</a> of all reported studies of faecal transplants to treat C. difficile infection found poo transplants to be effective in over 90% of cases. Recurrence of infection is rare and there has not been a single report of adverse side effects. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=421&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=421&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=421&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=529&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=529&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18210/original/dp3qf2j8-1354246897.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=529&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Antibiotics may be thwarting our best efforts to stave off infection by messing with the delicate ecosystem of the gut.</span>
<span class="attribution"><span class="source">sparktography</span></span>
</figcaption>
</figure>
<p>As simple as the procedure sounds, we don’t yet fully understand how faecal transplants work. This may be set to change, however, as global efforts to make sense of the staggering complexity of our microbiome ramp up. <a href="http://commonfund.nih.gov/hmp/">The Human Microbiome Project</a> funded by the National Institutes of Health in the United States, and the European Commission-funded <a href="http://www.metahit.eu/">Metagenomics of the Human Intestinal Tract</a> project, are beginning to define our most intimate microbial co-habitants.</p>
<p>As we grapple with the complexity of our microbial ecology, perhaps we will discover which specific microbes are responsible for reigning in C. difficile during a faecal transplant. It might be a single species, or perhaps it’s a combination of several. </p>
<p>By identifying the microbes responsible, the poo transplant could eventually be replaced with a probiotic pill containing only the necessary species required to right the system. The “yuck” factor would be removed. </p>
<p>Or perhaps there are particular foods and supplements that we could consume as prebiotics to favour the growth of healthy bacteria when superbugs take hold.</p>
<p>In the meantime, the simplest, and perhaps most obvious way of modifying our gut ecology when superbugs take hold may well be to transfer an ecosystem en masse, through the under-appreciated technique of the poo transplant.</p>
<hr>
<p><strong>This is the eighth article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10755/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dyani Lewis receives funding from the Department of Health and Ageing.</span></em></p>Antibiotics joined our growing arsenal of weapons in the fight against disease over seventy years ago. Their target – the bacterial infections that putrefied our wounds, filled our lungs with pneumonia…Dyani Lewis, Sexual health researcher, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/109902012-12-05T01:18:28Z2012-12-05T01:18:28ZUnblocking the pipeline for new antibiotics against superbugs<figure><img src="https://images.theconversation.com/files/18295/original/4ycq4p57-1354580066.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The days when there was always a new antibiotic just around the corner to treat the latest superbug are long gone.</span> <span class="attribution"><span class="source">Ralph Keating</span></span></figcaption></figure><p>Most experts considering the subject agree that the antibiotic development pipeline is not sufficient by a long shot. The days when there was always a new antibiotic just around the corner to treat the latest superbug are long gone.</p>
<p>Still, fixing the antibiotic pipeline is not rocket science. The main difficulty lies in finding molecules that enter the bacterial cell, stay there and inhibit growth of the bug without being toxic to us. What prevents us from overcoming this difficulty is that the number of people working on the problem has shrunk to historically low levels.</p>
<p>Continuing consolidation (mergers and acquisitions) among large pharmaceutical companies, and the outright abandonment of antibiotic research by these companies has severely impacted our ability to come up with new ideas, new approaches and new molecules. And the lack of experience and training of academics in the science of drug discovery undermines current efforts in the public sector.</p>
<p>We can’t make scientific discovery any easier, but there are three areas over which we have some control.</p>
<h2>Regulatory reform</h2>
<p>First and foremost, we need regulatory reform. One of the reasons industry has abandoned the area is increasing regulatory stringency, which translates into larger clinical trials and greater development expense – and the accompanying regulatory uncertainty for antibiotics. This has mainly been a problem at the <a href="http://www.fda.gov/">US Food and Drug Administration</a> (FDA). While the FDA has recently started to undertake such reform, its precise requirements for antibiotic development are not yet known, making it harder for companies to commit to expensive trials.</p>
<p>One area where the United States has been leading is in the idea of using data in one indication (such as abdominal infection) to support data in another (such as urinary tract infection). In such cases, companies could run one trial in each indication and get approval for both. While this is helpful, the trial required for each indication still has to be feasible and affordable, which is currently not the case for many antibiotic trials.</p>
<p>Regulators are working on the use of small, streamlined trials to get antibiotics targeting specific resistant bacteria to the market quickly to help those patients in need of these life-saving drugs. Since this is a relatively small number of patients compared to the general population, and since the dossiers supporting these products will, in one way or another, have to show superiority over existing drugs (such as activity against superbugs), we can anticipate paying a high price for them.</p>
<h2>Economic factors</h2>
<p>Two approaches can address the economic factors that have led industry to leave antibiotic research and development. The kind of push incentive that has been provided by government agencies such as the <a href="http://www.phe.gov/about/barda/pages/default.aspx">Biomedical Advanced Research and Development Authority</a> (BARDA) in the United States has been enormously important for providing confidence that industry can develop antibiotics without sinking unrealistic amounts of money into late-stage trials. </p>
<p>Glaxo Smith-Kline, for instance, was awarded up to $97 million for the development of an exploratory new antibiotic. Such push incentives have a quick and positive impact on the net present value of products by reducing initial expense outlays.</p>
<p>The other economic factor we can control is drug pricing. This is a contentious issue that’s not often openly discussed in Australia. We’re happy to pay tens of thousands of dollars for cancer drugs but we expect to pay only a few dollars for antibiotics that can be incredibly effective in curing disease, but that are only taken for a few weeks.</p>
<p>Currently, Australia is not willing to pay for drugs that don’t show a “clear advantage” over older, cheaper drugs. But what does “clear advantage” mean? Sometimes it might be an expanded spectrum of activity; for example carbapenems are able to kill more types of bacteria than cephalosporins. Sometimes it might mean an oral form of a drug taken in pill form that might otherwise be lacking. But in Australia’s pricing system, the comparison is always to the price of the cheaper drug within the same class.</p>
<p>Australia is almost unique in the world in this regard, and doesn’t take into account the potential long-term health benefits of newer drugs compared to older ones. Such benefits include fewer side effects, faster cure times, better compliance with the dosing schedule or other improvements that might not be obvious in clinical trial data. Taking a pill once a day, for instance, is easier to remember than taking one three times a day.</p>
<p>One area we don’t need to fix is the market itself. There’s been discussion of pull incentives where governments provide a guaranteed market for antibiotics active against key drug-resistant superbugs. Given the evolving dominance of emerging economies in the global antibiotic market and the high incidence of superbugs in many of these countries, we think that the market will provide enough incentive itself.</p>
<h2>Better training</h2>
<p>Finally, we need to train our academic researchers in the science of drug discovery. We suggest using government funds to provide such training within industry in exchange programs. Academics should be allowed, even encouraged, to spend time with partner pharmaceutical companies and “learn by doing.”</p>
<p>So here’s our five-point plan for new antibiotics:</p>
<ul>
<li><p>regulatory reform;</p></li>
<li><p>streamlined clinical trials for antibiotics against resistant superbugs;</p></li>
<li><p>better antibiotic pricing policies;</p></li>
<li><p>marketing in emerging economies and;</p></li>
<li><p>training for academic researchers.</p></li>
</ul>
<p>This will all take political will and funding, but it will get us where we need to be – one step ahead of the superbugs.</p>
<hr>
<p><strong>This is the sixth article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10990/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Cooper receives funding from the NHMRC for antibiotic research.</span></em></p><p class="fine-print"><em><span>David Shlaes - Consults for - AZ Achillion x Abingworth U. Queensland
GSK x Actelion x Novo U. Waterloo
Sanofi-Aventis X Allecra x PhaseIV
Armethion x Ventech
AtoxBio x Longitude
Cempra x Edmond de Rothschild
Crestone x ZS Associates
Indel x
Nabriva x
Nosopharm x
Novobiotics x
Oculusis x
Polyphor x
Rempex x
Rib-X x
Tetraphase x </span></em></p>Most experts considering the subject agree that the antibiotic development pipeline is not sufficient by a long shot. The days when there was always a new antibiotic just around the corner to treat the…Matthew Cooper, Prof. Institute for Molecular Bioscience, The University of QueenslandDavid Shlaes, Anti-Infectives ConsultingLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/107272012-12-04T19:47:47Z2012-12-04T19:47:47ZThe last stand: the strongest of the superbugs and their antibiotic nemesis<figure><img src="https://images.theconversation.com/files/18300/original/tp55wtrs-1354581574.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria are like little towns surrounded by walls that have gates for letting supplies in and waste out.</span> <span class="attribution"><span class="source">Michael Douglas Bramwell</span></span></figcaption></figure><p>New Delhi metallo-beta-lactamase 1, or NDM-1 bacteria as they’re commonly known, are among the most dangerous superbugs to have emerged in recent years. They’re resistant to almost all the antibiotics we’ve discovered to date. </p>
<p>NDM-1 was first described in 2009 in a Swedish patient who’d been in New Delhi, India. It’s a gene that can be transferred between bacteria, which allows them to produce a very powerful enzyme that destroys what was previously our last line of defence – the <a href="http://www.bmj.com/content/344/bmj.e3236">carbapenem antibiotics</a> (distant cousins of penicillin that were the last standard antibiotics still able to kill some of the earlier superbugs).</p>
<p>Now there’s only one antibiotic left that really works against this new generation of superbugs – a forgotten antibiotic called <a href="http://www.uptodate.com/contents/colistin-an-overview">colistin</a>.</p>
<h2>Forgotten but not gone</h2>
<p>Colistin has been around for a long time. It was originally discovered in 1949 and was in clinical use until the 1970s, when it was replaced by newer antibiotics that were better against more types of bacteria, and that had fewer side effects.</p>
<p>So colistin vanished from use for a while – and this has been its saving grace. Because the antibiotic hasn’t been used for such a long time, bacteria didn’t have the chance to develop resistance against it and pass it around. Most superbugs emerging now haven’t seen colistin before and remain susceptible to the drug.</p>
<p>But there are three big drawbacks to using this antibiotic.</p>
<p>First, it can have severe side effects, including damage to the kidneys. Clinicians are getting on top of this with improved dosing schedules and a better understanding of how to handle other side effects. But patients on colistin can still suffer from kidney damage.</p>
<p>Colistin only works against certain types of bacteria – it’s not a “wonder drug” that kills all superbugs (for instance, it does not work against MRSA). And colistin-resistant bacteria are already appearing, so we can’t rely on this antibiotic to work forever.</p>
<h2>Why so strong?</h2>
<p>To understand what makes colistin different from other antibiotics and why it still works, we need to understand a little more about how bacteria are built and how they work.</p>
<p>Just imagine that a bacterium is like a little town: it has its own factories to produce things it needs, its own power plant, a central library with the master plans for all things produced in the factories, and a steady stream of raw materials coming in from the outside. For protection, the town is surrounded by a wall that has quite a few gates – some guarded, some unguarded – through which all the produce and raw materials come in and waste gets carried out.</p>
<p>All bacteria are much the same on the inside, even though they may produce slightly different things in their factories and use some different raw materials. But they have major differences in the barriers they make to protect themselves from attack. </p>
<p>Some bacteria build very strong walls on the outside (think thick medieval stone walls) to keep things out that they don’t want inside. Most antibiotics need to get to the inside of bacteria to destroy them. They do this by either sneaking in through the gates or by weakening and breaking down parts of the wall.</p>
<p>Other bacteria have only a somewhat flimsy wall that surrounds them but they have strong defences (think barbed wire) on the outside of the wall and their gates are better guarded. This makes it a lot harder for antibiotics to get inside and they can’t attack the town wall directly because the barbed wire is in the way.</p>
<p>This is where colistin comes in. It’s too big to get in through the gates and it can’t break through those strong town walls of the first type of bacteria, but it has the ability to cut through barbed wire fences. Once through, the flimsy wall behind is no real obstacle any more and colistin can go and wreak havoc inside the bacterium and kill it.</p>
<p>But if previous experience with antibiotics has taught us anything, it’s that the bacteria will find a way around this. There are already some bacteria that managed to strengthen that barbed wire fence and have become resistant to colistin.</p>
<p>Colistin originally comes from one particular species of bacteria (Paenibacillus polymyxa). As a mechanism to avoid being killed by the colistin they produce, these bacteria also make an enzyme that can destroy colistin. It doesn’t seem likely at the moment, but should the gene for this enzyme manage to get transferred to a superbug there will be truly nothing left to stop them. The only option left to save a patient’s life will be surgery, including amputation. </p>
<p>As in pre-antibiotic times getting an infection after something simple such as standard surgery on your knee may mean that you could lose the whole leg!</p>
<hr>
<p><strong>This is the fifth article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10727/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Matthew Cooper receives funding from the NHMRC for antibiotic research</span></em></p><p class="fine-print"><em><span>Bernd Becker 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 Delhi metallo-beta-lactamase 1, or NDM-1 bacteria as they’re commonly known, are among the most dangerous superbugs to have emerged in recent years. They’re resistant to almost all the antibiotics…Bernd Becker, Senior Research Officer, The University of QueenslandMatthew Cooper, Prof. Institute for Molecular Bioscience, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/106992012-12-04T00:03:20Z2012-12-04T00:03:20ZThe hunt is on for superbugs in Australian animals<figure><img src="https://images.theconversation.com/files/17807/original/3n4d3y9g-1353371548.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Australia's food chain has among the lowest rates of antibiotic resistance, but new threats call for stronger monitoring.</span> <span class="attribution"><span class="source">Eli Duke</span></span></figcaption></figure><p>Australia has some of the world’s most conservative restrictions on using antimicrobial drugs in livestock. Possibly as a consequence, we have some of the lowest rates in the world of antibiotic resistance in the bacteria (such as Salmonella and Campylobacter) that cause food poisoning. </p>
<p>Australian producers do not use broad-spectrum antibiotics such as <a href="http://en.wikipedia.org/wiki/Quinolone">fluoroquinolones</a> or <a href="http://en.wikipedia.org/wiki/Gentamicin">gentamicin</a> in livestock production. The antibiotic <a href="http://en.wikipedia.org/wiki/Ceftiofur">ceftiofur</a> is governed by strict label requirements. </p>
<p>However, Australia is increasingly importing fresh food, including vegetables, from countries where these antimicrobial drugs are used indiscriminately in both animals and humans. Australia’s primary producers are under great pressure. They have to compete with cheap imported products that are often of inferior quality and may come from countries where the use of antibiotics in livestock is not so tightly regulated.</p>
<p>Australia has no coordinated national program monitoring antibiotic resistance in livestock or companion animal pathogens. Resistance in these key pathogens is a major driver throughout the world of the use of antimicrobial drugs for animals as well as humans. </p>
<p>Just like doctors, when veterinarians encounter disease in animals they may often take samples, such as urine from a dog with suspected infection of the bladder, and submit the samples to a specialised veterinary microbiology laboratory. The laboratory will culture the urine, identify the bacteria and tell the veterinarian which antibiotics the organism is sensitive to. This helps them make the correct treatment choice.</p>
<p>Right now, most veterinary microbiology laboratories in Australia are only keeping the bacteria they isolate from animals for a short time. Saving the bacteria for longer means we can accurately measure rates of resistance to all classes of antibiotic across the nation. </p>
<p>In a new project, a network of over 20 university-based, private and government veterinary microbiology laboratories will submit all the isolates they obtain to The University of Adelaide. Such “routine surveillance” is already practiced in Australia for Escherichia coli (E. coli) and staphylococci obtained from cases of infection in humans. It is a major weapon in the fight against antibiotic resistance.</p>
<p>Previous small-scale studies have shown the risk of antimicrobial resistance organisms coming through the Australian food-chain is extremely small. However, a national surveillance programme is required to confirm this. It will also quickly identify any hot pockets of emerging resistance so they can be immediately dealt with. </p>
<p>The hunt for superbugs in Australian animals may confirm that we have low rates of resistance to important classes of drug relative to other countries. This will be good news for both our producers and consumers. But we should not be complacent. </p>
<p>Just like their medical counterparts, veterinarians are end users of antibiotics. They need to work in tandem with health-care professionals so that they don’t overprescribe antibiotics, practice good infection control such as regular hand disinfection and investigate viable alternatives to antibiotics for the treatment and control of bacterial diseases, particularly in livestock.</p>
<p>One overlooked but important area is whether resistance in E. coli and staphylococci is causing infections in companion animals. </p>
<p>Treatment for our loved pets when they succumb to illness closely mirrors how we treat people in hospitals. Recent research has shown that humans can readily transmit E. coli that cause urinary tract infections and staphylococci that cause skin and soft tissue infections to their pets. Pets can then transmit them back to humans. </p>
<p>The E. coli strains normally live in the intestine. There, they do no harm. But they cause infections when they gain entry to a normally sterile site, such as the bladder. Highly resistant strains have emerged and spread globally in humans and have recently been identified in dogs. The problem is currently small, but increased vigilance is required to keep it that way.</p>
<p>Over the next few years, we hope the animal surveillance data will positively influence the prescribing practices of veterinarians in the field, whether they work with livestock, companion animals, or both. It will also be used as an educational resource in veterinary schools to spread prudent use of antibiotics to the next generation of veterinarians. </p>
<hr>
<p><strong>This is the fourth article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10699/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr Darren Trott is a veterinarian who teaches microbiology at the School of Animal and Veterinary Sciences at The University of Adelaide. He has received funding from Pfizer and Bayer Animal Health to conduct resistance monitoring in animal pathogens in Australia as a requirement for the registration of new antibiotic products.</span></em></p>Australia has some of the world’s most conservative restrictions on using antimicrobial drugs in livestock. Possibly as a consequence, we have some of the lowest rates in the world of antibiotic resistance…Darren Trott, Senior Lecturer Veterinary Microbiology, University of AdelaideLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/94922012-12-03T19:42:53Z2012-12-03T19:42:53ZWe can beat superbugs with better stewardship of antibiotics<figure><img src="https://images.theconversation.com/files/18271/original/b7qq3gyk-1354506134.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Only by prescribing antibiotics smarter instead of broader will we keep superbugs at bay.</span> <span class="attribution"><span class="source">lamentables/Flickr</span></span></figcaption></figure><p>Antibiotic resistant bacteria are becoming a major problem. <a href="http://www.mja.com.au/journal/2011/194/6/antibiotic-resistance-emerging-threat-public-health-urgent-call-action">Calls to action</a> on increasing <a href="http://www.reactgroup.org">rates of resistance</a> have been made by the <a href="http://www.who.int/dg/speeches/2012/amr_20120314/en/index.html">World Health Organization</a>, the US Centers for Disease Control <a href="http://www.cdc.gov/drugresistance/index.html">(CDC)</a>, and by the Australian Societies for Infectious Diseases (<a href="http://www.asid.net.au">ASID</a>) and the Australian Society for Antimicrobials (<a href="http://www.asainc.net.au">ASA</a>). </p>
<p>And the media regularly features articles about <a href="http://www.google.com/search?hl=en&gl=au&tbm=nws&q=superbugs">superbugs</a> and <a href="http://www.couriermail.com.au/news/queensland/mega-superbug-research-gets-funding-boost/story-e6freoof-1225826412108">mega-superbugs</a>. So why, if everyone is aware of the problem, are we still not winning the fight?</p>
<h2>Drivers of resistance</h2>
<p>Antibiotic resistance is caused by excessive antibiotic use. If bacteria aren’t exposed to antibiotics, there’s no impetus for them to become resistant. But much modern medicine would be impossible without antibiotics (most surgery, for instance) so they are a necessary “evil”. </p>
<p><a href="http://jac.oxfordjournals.org/content/early/2012/09/06/jac.dks338">More than 80%</a> of antibiotics are prescribed in general practice, and much of this is for upper respiratory tract infections (such as colds). These are mostly caused by viruses and almost never need antibiotics. </p>
<p>Patients treated with antibiotics are almost <a href="http://www.ncbi.nlm.nih.gov/pubmed/18953388">three times more likely</a> to experience a side effect (mainly nausea), for no benefit because antibiotics won’t affect the duration of their illness. And <a href="http://www.bmj.com/content/340/bmj.c2096?ijkey=33d428d6b19da413b19cbb4cff68d8324155e02f&keytype2=tf_ipsecsha">resistance can develop</a> even after a short course of antibiotics.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18255/original/52cfbnkh-1354496047.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Colds are mostly caused by viruses and almost never need antibiotics.</span>
<span class="attribution"><span class="source">Image from shutterstock.com</span></span>
</figcaption>
</figure>
<p>Hospital patients are usually sicker than patients who visit a GP. Sometimes, they’re very sick and need urgent treatment. In severe infections, the time delay until antibiotics are given is a <a href="http://www.ncbi.nlm.nih.gov/pubmed/16625125">major risk for mortality</a>. </p>
<p>Since antibiotic resistance is now a fact of life in hospitals around the world, it’s understandable that doctors want to give their patients the best treatment available. This can lead to “antibiotic armageddon” where the biggest, most broad-spectrum antibiotic is felt to be the best way to proceed.</p>
<p>Australia has excellent <a href="http://www.tg.com.au">prescribing guidelines</a> that are easily available for doctors to refer to when prescribing antibiotics. In practice, though, studies in <a href="http://www.ncbi.nlm.nih.gov/pubmed/22697156">Australia</a> and <a href="http://www.ncbi.nlm.nih.gov/pubmed/16735152">elsewhere</a> show fairly consistently that only between half and three-quarters of antibiotic prescriptions are in keeping with such guidelines.</p>
<p>I performed an audit of antibiotics prescribed to in-patents of a hospital I worked at. It was based on a review of their medication charts and comparison with <a href="http://www.tg.com.au">Australian Therapeutic Guidelines</a>. This is what I found:</p>
<ul>
<li><p>dosing errors – 13%; </p></li>
<li><p>choice of drug different from guidelines – 11%; </p></li>
<li><p>unnecessarily prolonged treatment – 8% and;</p></li>
<li><p>antibiotics not required at all – 8%. </p></li>
</ul>
<h2>The three “Es”</h2>
<p>The solution can be simplified into three “Es” – education, expectations, and enforcement.</p>
<p>As medicine becomes more complex, it’s increasingly difficult to teach junior doctors everything they “must know” in order to practice. Education on good prescribing habits and the importance of rational antibiotic use are critical when doctors are in the formative stage of their careers. </p>
<p>Doctors’ expectations are also important. Not every fever requires antibiotics and broader-spectrum isn’t always better are the key messages to teach.</p>
<p>Although there are <a href="http://www.nps.org.au/medicines/antibiotics_for_respiratory_tract_infections/what_are_antibiotics_and_how_do_they_work/antibiotics_dont_kill_viruses">many</a> <a href="http://webarchive.nationalarchives.gov.uk/+/www.dh.gov.uk/en/Publichealth/Patientsafety/Antibioticresistance/FAQ/DH_082655">campaigns</a> <a href="http://www.cdc.gov/getsmart/antibiotic-use/know-and-do.html">aimed</a> at the public about <a href="http://www.dh.gov.uk/health/files/2012/09/Download-Poster-Antibiotics-will-not-get-rid-of-your-cold-ref.pdf">antibiotics for colds</a>, around half of patients seeing a GP still expect <a href="http://www.ncbi.nlm.nih.gov/pubmed/15128681">such a prescription</a>. And although only half expect it, 73% receive one. Those who don’t are <a href="http://www.ncbi.nlm.nih.gov/pubmed/9393228">twice as likely</a> to present for another consultation. </p>
<p>There are two factors at play here – patients’ expectation of a prescription and general practitioners’ understanding of what patients expect. More worrying still is that doctors think that <a href="http://jac.oxfordjournals.org/content/early/2012/09/04/jac.dks338">their prescribing</a> doesn’t impact resistance.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=628&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=628&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=628&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=790&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=790&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18256/original/dm85cy2c-1354496228.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.</span>
<span class="attribution"><span class="source">NIAID/NIH</span></span>
</figcaption>
</figure>
<p>The result is a <a href="http://en.wikipedia.org/wiki/Tragedy_of_the_commons">tragedy of the commons</a> – patients may be aware of the risks of antibiotics in general, but feel the benefit for them outweighs the risks to the community, as superbugs only happen to someone else. In fact, the opposite is true - for viral infections patients receive no benefit from antibiotics but all of the risk.</p>
<p>In addition to education, a well-designed antibiotic stewardship program can <a href="http://www.jstor.org/stable/10.1086/664909">significantly improve</a> antibiotic use in hospitals. As well as improving care quality, these programs can also reduce costs and decrease length of stay in hospital and the rates of hospital-acquired infection. </p>
<p>Although doctors often bristle at restrictions on their practice, acceptance of these programs is <a href="http://www.ncbi.nlm.nih.gov/pubmed/19383062">surprisingly high</a>.</p>
<p>Antibiotic resistance is currently seen as a clinical problem for doctors and hospitals, rather than a more general health issue. The key to overcoming it is reframing resistance as a problem of public health importance and getting the public more <a href="http://youtu.be/WNfFQI18ABI?hd=1">engaged</a>, as has been done with <a href="http://www.cdc.gov/handhygiene/PDF/CDC_HandHygienePoster.pdf">hand washing</a>. Rather than patients asking for a prescription, we need them to ask “do I really need antibiotics for this?”</p>
<p>Superbugs are complex and pose a serious health threat. Only by working together, and prescribing smarter instead of broader, will we keep them at bay.</p>
<hr>
<p><strong>This is the third article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/9492/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Trent Yarwood does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations. The opinions in the article are his own and do not necessarily reflect those of his employer.</span></em></p>Antibiotic resistant bacteria are becoming a major problem. Calls to action on increasing rates of resistance have been made by the World Health Organization, the US Centers for Disease Control (CDC…Trent Yarwood, Infectious Diseases Physician, Associate Lecturer, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/107652012-12-03T00:00:51Z2012-12-03T00:00:51ZSuperbugs, human ecology and the threat from within<figure><img src="https://images.theconversation.com/files/18114/original/j2tw45w3-1354080437.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria can quickly adapt and overcome the antibiotics that used to kill them.</span> <span class="attribution"><span class="source">Image from shutterstock.com</span></span></figcaption></figure><p>At the beginning of the 20th century, around <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4829a1.htm">one in three children</a> in countries such as Australia and the United States died of infection before the age of five. But since Howard Florey <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)41962-8/fulltext">first described the power of penicillin</a> in 1947 and antibiotics became widely available, we have come to expect that life-threatening bacterial infection can be easily managed. </p>
<p>Early antibiotic therapy still means the difference between life and death for a previously healthy young person with a severe blood infection. However, we have long known that bacteria can quickly adapt to overcome the antibiotics that used to kill them. These antibiotic-resistant bacteria are often referred to as “superbugs”. </p>
<h2>From common bacteria to superbug</h2>
<p>Many disease-causing bacteria are only occasional visitors to our body, quietly coming and going. These visitors sometimes cause severe infection: the classic example is the <a href="http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Staphylococcus_aureus_golden_staph">golden staph</a> (Staphylococcus aureus), which we seek to control with hygiene measures such as hand washing to prevent transmission, and antibiotics to treat infection. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=377&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=377&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=377&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=474&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=474&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18185/original/f4zdsphd-1354232983.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">MRSA bacteria.</span>
<span class="attribution"><span class="source">NIAID NIH</span></span>
</figcaption>
</figure>
<p>We know that major genetic mutations in bacterial populations are rare, as in most populations, but these bacterial communities are huge. Like <a href="http://www.princeton.edu/%7Ehau/ReprintLinks/Darwin_Finches.pdf">Darwin’s finches</a>, changes tend to take over a population if they enhance biological success. </p>
<p>Subtypes of golden staph developed the capacity to survive antibiotics soon after they met them. Antibiotic-resistant variants of golden staph such as <a href="http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cd33_mrsa_brochure.pdf">Methicillin Resistant Staphylococcus aureus</a> (or MRSA) cause skin, bone and joint, and soft tissue infections (abscesses) and occasionally lethal blood poisoning (septicaemia). These resistant golden staph are now very common, both in hospitals and in the community.</p>
<p>Other bacteria work differently. <a href="http://www.wisegeek.com/what-is-e-coli.htm">Escherichia coli</a> (E. coli), and bacteria like it, exist as permanent populations in our own gut ecosystem, where they are specifically adapted to live. Most strains of E. coli are harmless, but some can cause <a href="http://en.wikipedia.org/wiki/2011_Germany_E._coli_O104:H4_outbreak">food poisoning</a>, urinary tract infections (UTIs) and other serious infections. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=896&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=896&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=896&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1126&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1126&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18187/original/65rcrh5n-1354233554.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1126&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">E coli</span>
<span class="attribution"><span class="source">CDC Public Health Image Library</span></span>
</figcaption>
</figure>
<p>Bacteria like E. coli have always exchanged advantageous genes quickly and efficiently, sharing a big gene pool. The genes move around mostly in specialised packages called <a href="http://askabiologist.asu.edu/plasmids">plasmids</a>, which shuttle between bacteria. This system provides the bacteria with an enormous capacity to adapt to change. </p>
<p>It’s not surprising then, that this gene pool now includes many antibiotic-resistance genes on plasmids. This process of pick-up of a resistance plasmid from the gene pool takes only minutes and can even occur during treatment.</p>
<p>So, what does this mean for us? If an E. coli spills into the bloodstream from a simple urinary tract infection, the infection can usually be treated with modern antibiotics, even if the infection overwhelms the body, as in cases of <a href="http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001689/">septic shock</a>. However, if that E. coli can obtain a resistance plasmid and overcome the antibiotics, even the best intensive care treatment may not be able to save the patient’s life. </p>
<h2>The threat from within</h2>
<p>While MRSA was the superbug of the recent past, the biggest future threat may be from species that are part of our own normal ecology, such as E. coli. This gene pool story is the main reason. </p>
<p>To understand it, you might think of the gut as like a rainforest, home to a diverse range of flora (the bacterial “microflora”). But just as weed species can threaten a rainforest, plasmids carrying resistance genes can dominate the gut’s bacterial gene pool. </p>
<p>In this ecosystem, resistance plasmids and related (non-resistant) plasmids compete for ecological turf. These plasmids are designed to “stick” in bacteria and once in, tend to be permanent - staying long after the antibiotics are gone.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=904&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=904&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=904&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1136&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1136&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18227/original/fbp882c8-1354431022.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1136&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Just like weeds and native plants in a rainforest, resistance plasmids and non-resistant plasmids compete for ecological turf in the gut.</span>
<span class="attribution"><span class="source">igormazic</span></span>
</figcaption>
</figure>
<p>This is the nub of the problem. Because disease-causing strains are more likely than their harmless cousins to be treated with antibiotics, they are more likely to have resistance plasmids. </p>
<p>It’s therefore logical to expect antibiotics to help disease-causing sub-populations to flourish within each bacterial species. This should be true for E. coli and all bacteria like it (such as <a href="http://www.cdc.gov/HAI/organisms/klebsiella/klebsiella.html">Klebsiella</a>, <a href="http://www.cidmpublichealth.org/resources/pdf/bsp/bsp27-feb-12.pdf">Salmonella</a>).</p>
<p>So, if this is generally how things work, does this mean that we’ll all be at greater risk of untreatable food poisoning and UTIs in future? The short answer is yes. This is the natural response of an ecosystem (in this case, the bacteria of the human gut) to selection pressure (in this case, antibiotic exposure). </p>
<p>It’s important to note that the battle between resistant and naturally occurring bacteria isn’t just happening within our own guts – we share our gut bacteria with humans and animals all over the world. So antibiotic exposure in one place leads to antibiotic resistance in another. </p>
<p>Here in Australia, E. coli infection responds to standard hospital-type antibiotics more than 19 times out of 20, while in India this may be only one in three. These two figures may well come closer together over time.</p>
<h2>Looking ahead</h2>
<p>A healthy gut microflora is important for our well-being – disturbances from antibiotics can result in disease such as <a href="http://www.cidmpublichealth.org/resources/pdf/bsp/bsp18-june-10.pdf">Clostridium difficile</a> (which causes diarrhoea) and <a href="http://www0.health.nsw.gov.au/factsheets/sexualhealth/thrush.html">thrush</a>. </p>
<p>We need to think of the human (and animal) gut microflora as an inter-connected global ecosystem, and ask ourselves if we are managing it well. If we remain heedless of this risk, we may pass a tipping point beyond which this vital ecosystem, the gut microflora, cannot recover. </p>
<p>Thankfully, rapid advances in our understanding of microbial ecology and gene transmission should allow us to manage and possibly even restore this ecosystem. As long as we act in time.</p>
<hr>
<p><strong>This is the second article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part one:</strong> <a href="https://theconversation.com/washing-our-hands-of-responsibility-for-hospital-infections-10652">Washing our hands of responsibility for hospital infections</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10765/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jon Iredell receives funding from the National Health and Medical Research Council of Australia.</span></em></p>At the beginning of the 20th century, around one in three children in countries such as Australia and the United States died of infection before the age of five. But since Howard Florey first described…Jon Iredell, NHMRC Practitioner Fellow; head of the NHMRC Centre for Research Excellence in Critical Infection, University of SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/106522012-12-02T19:40:50Z2012-12-02T19:40:50ZWashing our hands of responsibility for hospital infections<figure><img src="https://images.theconversation.com/files/18111/original/dq9x6k7v-1354078805.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Around 180,000 hospital-acquired infections occur in Australia each year.</span> <span class="attribution"><span class="source">Hospital image from shutterstock.com</span></span></figcaption></figure><p>Infections, like taxes, are inevitable (to paraphrase Benjamin Franklin). Most are acquired in the community and the dangerous ones are, in the main, very difficult to prevent. But many infections are preventable and, regrettably, most of these occur as a consequence of hospitalisation. </p>
<p>It has been estimated that around <a href="http://www.pc.gov.au/__data/assets/pdf_file/0016/93040/09-chapter6.pdf">180,000 hospital-acquired infections</a> occur in Australia each year and these infections result in almost two million additional days in hospital. </p>
<p>About ten years ago, health systems <a href="http://apps.who.int/medicinedocs/documents/s16320e/s16320e.pdf">belatedly acknowledged</a> that the means of reducing the transmission of infection in hospitals was right before our eyes: on our hands, to be precise.</p>
<p>Even before bacteria had been identified as the cause of contagion, Dr Ignaz Semmelweis, a Hungarian-born physician working in the Vienna Hospital in the 1840s, <a href="http://qualitysafety.bmj.com/content/13/3/233.full">proved</a> that his dirty-handed medical staff were responsible for the high death rate of women after childbirth. </p>
<p>He observed that women who gave birth who were attended by medical staff had a 13% death rate from “puerperal sepsis” (now known to be caused by <a href="http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Streptococcal_disease">Group A Streptococcal infection</a>). The women who gave birth in the midwife-led ward had a sepsis rate of only 2%. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=805&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=805&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=805&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1011&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1011&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18110/original/xsjqvvf6-1354078448.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1011&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Ignaz Semmelweis, 1858</span></span>
</figcaption>
</figure>
<p>When Semmelweis made his doctors and medical students wash their hands in a chlorinated solution after they had performed a postmortem on a recently deceased mother – and before they went next door to the delivery ward to attend another birth – the death rate fell to 2% within a month. </p>
<p>Semmelweis’ findings were rejected by his peers who refused to believe that medical staff could be responsible for the transmission of disease. Nevertheless, within decades the germ theory of infectious diseases had been universally accepted. The ability of invisible micro-organisms to cause serious illness and death became a plank of Western medicine. </p>
<p>By the turn of the 20th century surgeons learnt how to minimise (but not eliminate) the risk of surgical infection through sterilisation of instruments, the creation of clean operating theatres and the wearing of sterile gowns and gloves. </p>
<p>The introduction of antibiotics in the mid 20th century further reduced the risk of post-operative infection and the wards that had been full of patients suffering from dreadful infections soon emptied out.</p>
<p>But over the next two generations the medical community lost much of its previous respect for germs. The increasing availability of antibiotics moved the emphasis of infection control from “prevention” to “cure” and it would not be until rates of antibiotic resistance were too high to be ignored that the medical profession started to re-learn the lessons of a previous century.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=347&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=347&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=347&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=436&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=436&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18109/original/5csxw9k7-1354078255.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=436&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Doctors with unwashed hands are like bees which move through the hospital, cross-infecting their patients.</span>
<span class="attribution"><span class="source">Image from shutterstock.com</span></span>
</figcaption>
</figure>
<p>In 2009 the World Health Organization released its <a href="http://apps.who.int/medicinedocs/documents/s16320e/s16320e.pdf">international guidelines on hand hygiene in health institutions</a>. They were inspired by the work of a modern-day Semmelweis, the Swiss-born <a href="http://www.who.int/gpsc/pittet_message/en/index.html">Didier Pittet</a>, who showed that increasing compliance with hand hygiene in his hospital from 48% to 66% reduced the rate of bacterial infection from 16.9% to 9.9% and more than halved the number of <a href="http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cd33_mrsa_brochure.pdf">antibiotic-resistant Staph aureus</a> (MRSA) infections.</p>
<p>Our antipodean Semmelweis, <a href="http://www.austinpathology.org.au/key-staff">Professor Lindsay Grayson</a>, leads the Commonwealth government-funded <a href="http://www.hha.org.au/">Hand Hygiene Australia</a>. As a result of this program, which promotes alcohol-based hand rub instead of soap and water, hand hygiene compliance in Australian hospitals has increased from less than 50% to <a href="http://www.hha.org.au/LatestNationalData.aspx">75.7%</a> in just three years. </p>
<p>Alcohol-based hand rub has been the “disruptive innovation” here. Washing hands with soap and water before and after every single patient contact takes too long. So staff apply hand rub and move between tasks while it is drying. Bottles of hand rub can be placed throughout the hospital, acting as constant reminders to perform hand hygiene.</p>
<p>But this remarkable achievement in hand hygiene was spoilt by one disturbing statistic – doctors only increased their compliance rate to <a href="http://www.hha.org.au/LatestNationalData.aspx">62.2% in 2012</a>, showing us to be the poorest performing of all the health professions.</p>
<p>It isn’t entirely clear why doctors take a more relaxed approach to infection control than our nursing and allied health colleagues. One reason may relate to modelling of behaviour – health professionals are tribal and follow the lead of their professional peers. At our medical school, we provide intensive education about hand hygiene for our medical students but when they enter the hospital they are influenced by the example of their often unwashed supervisors. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/18112/original/gqjst6b4-1354078935.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Alcohol-based hand rubs are more convenient than using soap and water.</span>
<span class="attribution"><span class="source">Image from shutterstock.com</span></span>
</figcaption>
</figure>
<p>One of my infectious diseases colleagues, <a href="http://www.austin.org.au/page/689">Paul Johnson</a>, says doctors with unwashed hands are like bees which move through the hospital, cross-infecting their patients with micro-organisms instead of pollen. Medical cultures, it would appear, are much harder to change than microbiological cultures.</p>
<p>We are now entering a time when the end of antibiotics may be in sight for many bacterial infections. This will have terrible implications for people who are at increased risk of infection, such as those with kidney, heart and bone marrow transplants. </p>
<p>It may become too risky to implant total hip and knee replacements and the risk of death from previously simple-to-treat infections such as pneumonia and urinary tract infections may return to that of the pre-antibiotic era.</p>
<p>So, part of the solution is, well, a solution: alcohol-based hand rubs that cost only a few cents per treatment and which dramatically reduce the chance of transmitting infections from patient to patient. Seems simple, really.</p>
<p><strong>This is the first article in Superbugs vs Antibiotics, a series examining the rise of antibiotic-resistant superbugs. Click on the links below to read the other instalments.</strong></p>
<p><strong>Part two:</strong> <a href="https://theconversation.com/superbugs-human-ecology-and-the-threat-from-within-10765">Superbugs, human ecology and the threat from within</a></p>
<p><strong>Part three:</strong> <a href="https://theconversation.com/we-can-beat-superbugs-with-better-stewardship-of-antibiotics-9492">We can beat superbugs with better stewardship of antibiotics</a></p>
<p><strong>Part four:</strong> <a href="https://theconversation.com/the-hunt-is-on-for-superbugs-in-australian-animals-10699">The hunt is on for superbugs in Australian animals</a></p>
<p><strong>Part five:</strong> <a href="https://theconversation.com/the-last-stand-the-strongest-of-the-superbugs-and-their-antibiotic-nemesis-10727">The last stand: the strongest of the superbugs and their antibiotic nemesis</a></p>
<p><strong>Part six:</strong> <a href="https://theconversation.com/unblocking-the-pipeline-for-new-antibiotics-against-superbugs-10990">Unblocking the pipeline for new antibiotics against superbugs</a></p>
<p><strong>Part seven:</strong> <a href="https://theconversation.com/a-peek-at-a-world-with-useless-antibiotics-and-superbugs-10984">A peek at a world with useless antibiotics and superbugs</a></p>
<p><strong>Part eight:</strong> <a href="https://theconversation.com/trading-chemistry-for-ecology-with-poo-transplants-10755">Trading chemistry for ecology with poo transplants</a></p>
<p><strong>Part nine:</strong> <a href="https://theconversation.com/new-antibiotics-whats-in-the-pipeline-10724">New antibiotics: what’s in the pipeline?</a></p><img src="https://counter.theconversation.com/content/10652/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>Infections, like taxes, are inevitable (to paraphrase Benjamin Franklin). Most are acquired in the community and the dangerous ones are, in the main, very difficult to prevent. But many infections are…Frank Bowden, Professor of Medicine at ANU; Senior Staff Specialist Infectious Diseases, ACT HealthLicensed as Creative Commons – attribution, no derivatives.