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The Antibiotic Crisis: Time to Wake Up!

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The Antibiotic Crisis: Time to Wake Up! THE ANTIBIOTIC CRISIS: TIME TO WAKE UP! The extent of the problem is enormous and alarming: In the European Union alone, 30,000 people die every year due to antibiotic resistance. In the United States, this figure is at least 23,000. Many more spend their lives suffering from significant physical disabilities. The still widespread idea that antibiotic resistance is some vague negative scenario of the future is clearly no longer true. The threat is real, it‘s here to stay and the time to act is now. Get an overview of the extent of the antibiotic crisis: how resistance develops, how it spreads and what role we all play - and what it specifically means today and in the future. Listen and watch what leading experts have to say and the alternatives and smart solutions on which researchers are currently working to outwit highly adaptable pathogens. Scientists, governments and global organizations are collecting data, attempting to formulate rules and action plans and implement programs to curb antibiotic resistance and its consequen- ces. The fight has already begun, its outcome has yet to be determined. To prevent falling back to the medical Middle Ages where every infection would potentially be a death sentence, every one of us needs to be aware of our responsibility - and face up to it. ANTIBIOTIC RESISTANCE What does “antibiotic resistance” mean to you? A severely ill patient in hospital, suffering from a germ that cannot be killed by any antibiotic known to man? This image is of course true, but it is only part of the picture. In reality, antibiotic resistance – or antimicrobial resistance, which as a broader term encompasses resistance caused by other microbes such as parasites, viruses and fungi – does damage that goes far beyond the confines of the hospital. It is a truly global social problem that will affect us all sooner or later if we don’t act together to stop it. So let’s talk about it. “This is a serious issue that is with us now, causing deaths. If it was anything else, people would be up in arms about it. […] We really are facing – if we don’t take action now – a dreadful post-anti- biotic apocalypse.” Professor Dame Sally Davies, Chief Medical Advisor to the UK government WHAT IS IT? Antibiotics are medicines used to prevent and treat bacterial infections. (They do NOT target viruses and are there- fore utterly useless for viral infections such as the common cold.) Antibiotics target, attack and kill most of the bac- teria involved. However, some bacteria mutate and become resistant to those antibiotics. Consequently, they survive the antibiotic onslaught and spread the very mutation that makes them immune. And when these resistant bacteria infect humans and animals, they are much harder to treat than those caused by non-resistant bacteria. In a lot of cases, doctors have run out of options altogether: In the European Union for instance, experts estimated that approximately 33,000 people die each year as a direct consequence of a bacterial infection resistant to anti- biotics (https://ecdc.europa.eu/en/news-events/33000-people-die-every-year-due-infections-antibiotic-resistant- bacteria). “Simply put, if we don’t address this problem now, we will no longer be able to treat common infections in the future. […] Some types of bacteria that cause serious infections in humans have already developed resistance to most or all of the available treatments.” Dr Marc Sprenger, Director WHO Antimicrobial Resistance Secretariat In a hospital environment, pathogens that develop antibiotic resistance are sometimes referred to as “superbugs”. (Probably because it takes the doctors’ superhuman effort to get rid of them.) Two main causes for antibiotic resist- ance have been identified: misuse (for instance against viral infections in humans) and overuse (for instance in agri- culture). HOW DOES IT HAPPEN? Bacteria can become resistant to antibiotics in several ways. Some bacteria can “neutralize” an antibiotic by changing it in a way that makes it harmless, and some have learned how to pump an antibiotic back outside of the pathogen before it can do any harm. Others can change their outer structure so the antibiotic has no way to even attach to the bacteria, let alone kill it. If even one bacterium becomes resistant to antibiotics, it can then multiply and replace all the bacteria that were pre- viously killed off. Exposure to antibiotics thus provides the so-called “selective pressure”, which makes the surviving bacteria more likely to be resistant. And the misuse and overuse of antibiotics – for instance when prescribed for a viral common cold – accelerates this process. HOW DOES IT SPREAD? The spreading of antibiotic resistance is an vicious cycle involving humans and animals. Poor hygiene, overuse and misuse of antibiotics all play a part. WHAT ARE THE CONSEQUENCES? The issue of antibiotic resistance has been troubling experts more or less since they were first discovered. But in recent years, the numbers that researchers from all over the globe have compiled make for grim reading, and should provide the impetus needed to instigate meaningful changes worldwide. These are the data of today. In addition, researchers have estimated how antibiotic resistance and its consequen- ces of disease and deaths would influence the world’s working population. They found that, compared to a world without antibiotic resistance, the world’s working age population would decrease drastically and the loss of gross domestic product would be significant. “The scale and nature of this economic threat could wipe out hard-fought development gains and take us away from our goals of ending extreme poverty and boosting shared prosperity.” Jim Yong Kim, President of the World Bank Group So is it all doom and gloom? No, not least because there are measures that every person can take to help the situation. WHY IS IT SO HARD TO DEVELOP NEW DRUGS? From the 1960s to the 1980s, pharmaceutical companies tried to counteract the issue by developing many new antibiotics. However, in the last few years, fewer and fewer antibiotics have been developed, steadily reducing the number of alternatives that can be used to treat germs that continuously develop new resistances. The pharmaceutical industry – both companies as well as institutes – are therefore called upon to renew their efforts to develop new antibiotics. The good news is that some pharmaceutical companies have done just that. Also, researchers are more than ever exploring alternatives to antibiotics as well as boosters to increase the antibiotics’ efficacy, and governments worldwide have joined in the battle against the global antibiotic resistance. The next chapter will tell you more. MEDICAL SOLUTIONS TO ANTIBIOTIC RESISTANCE The issue should be simple. Surely, if one antibiotic no longer works, it should be easy enough to develop a new one? Unfor- tunately, the situation regarding antibiotics is a bit more complicated. A quick dip into history will show why, and a slightly longer dip into the future will show how scientists are dealing with the issue. “We are already seeing infections that are resistant to all antibiotics – this is well known. Therefore, we must work extremely hard to safeguard the medications that are critical to human health, and facilitate research and development of new drugs.” Dr. Marc Sprenger, Director WHO Antimicrobial Resistance Secretariat A brief history of antibiotic resistance And ever since then, bacteria have developed resistances against nearly all antibiotics, simply because these drugs remove bacteria that are sensitive to them, leaving resistant bacteria behind to reproduce. The over-prescription of these drugs worldwide compounds the problem. 1943 1950 1953 1960 1967 1972 1985 1996 2000 2003 2010 erythromycin levooxacin tetracycline meth icillin gentamicin ceftazidime and imipenem linezolid ceftaroline penicillin vancomycin daptomycin 1950 1960 1970 1980 1990 2000 2010 1962 1968 1979 1996 methicillin-R erythromycin-R gentamicin-R levooxacin-R Staphylococcus Streptococcus Enterococcus Pneumococcus 1988 2001 2011 vancomycin-R linezolid-R ceftaroline-R Enterococcus Staphylococcus Staphylococcus 1959 1965 1987 1998 tetracycline-R penicillin-R ceftazidime-R imipenem-R Shigella pneumococcus Enterobacteriaceae Enterobacteriaceae You could call it an ancient ping-pong match between bacteria and science: Whenever scientists have developed or invented a new drug, bacteria have responded with adaptions that allow them to become resistant – until the next compound comes along. These adaptions can take a variety of forms. NEW ANTIBIOTICS: SETBACKS AND SUCCESSES In recent years, scientists have increased their focus on trying to develop new antibiotics; some of which have had more suc- cess than others. For example, in 2015 researchers hailed the discovery of two new antibiotics: Gulmirecin and disciformycin A and B were thought to be very effective against some bacteria already resistant against certain antibiotics. Unfortunately, the enthusiasm seems to have been unfounded, as no new studies have since been published on this subject. However, another antibiotic, also discovered in 2015 and called teixobactin, has just been used successfully to treat infec- tions in mice (animal studies are always the first step before testing drugs in humans). The researchers hope that teixobac- tin will be available as a drug in six to ten years’ time (https://newatlas.com/new-novel-antibiotic-success-animal-test- ing/53943/). And yet another antibiotic drug, the aptly named malacidin (“mal” = bad, “cide” = to kill), was recently observed to break down the cell walls of the still-dreaded MRSA pathogen mentioned above (Hover BM et al, Nature Microbiol 2018;3:415- 422). The team behind this discovery is now working to make malacidin available for mass production – which could take a while. BREAKING THE RESISTANCE In addition to new antibiotics, scientists have also looked at other options. For instance, non-antibiotic ‘adjuvant’ compounds, also known as ‘resistance breakers’ or ‘antibiotic potentiators’, can be administered together with the antibiotic.
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