Earlier this week, the World Health Organization released a list of 12 antibiotic-resistant organisms, which they have determined to be the "greatest threat to human health." The list contains pathogens such as carbapenem-resistant Enterobacteriaceae (CRE), which invariably kills half the people who are unlucky enough to acquire it. CRE and other such ‘superbugs’ are one of the biggest problems facing the future of medicine. Rapid bacterial evolution results in the emergence of superbugs that carry genes which make them resistant to antibiotics and extremely difficult to treat. In response to the emergence of a number of resistant organisms, the WHO Director General, Margaret Chan, has warned of a “post-antibiotic era” where even common infections could be deadly.
Antibiotic resistance is commonly attributed to antibiotic misuse and overuse. Fingers get pointed at lazy doctors who prescribe antibiotics for common colds and patients who do not adhere to their antibacterial treatment regimens correctly, allowing drug-resistant bacteria to flourish. The intensive farming industry is also to blame for pumping livestock and poultry full of antibiotics to sustain the mass production of meat. The considerable quantities of antibiotics used in factory farming serve to inadvertently create resistance genes that can jump between bacteria-- resulting in the creation of drug-resistant strains that can infect humans.
Although antibiotic misuse is an important cause of antibiotic resistance, it is certainly not the only one. Superbugs are a significant threat not only due to bacteria evolving too quickly, but also because antibiotics are evolving too slowly. In the arms race between bacteria and antibacterial agents, the bacteria are winning. To say that the development of antibiotics is lagging would be an understatement-- the antibiotic pipeline is basically bone dry. Both the total number of antibiotics brought to market and the discovery of novel classes of antibiotics have declined precipitously in recent decades. The number of new antibiotics on the market has been declining since the 1980s and almost every currently available antibiotic is derived from a class discovered before the mid 1980s. When bacteria become resistant to antibacterial agents, they tend to be resistant to multiple agents in the same class. Without the development of new types of antibiotics with unique mechanisms of action, we don’t stand a fighting chance against drug-resistant organisms.
Antibiotic resistance is commonly attributed to antibiotic misuse and overuse. Fingers get pointed at lazy doctors who prescribe antibiotics for common colds and patients who do not adhere to their antibacterial treatment regimens correctly, allowing drug-resistant bacteria to flourish. The intensive farming industry is also to blame for pumping livestock and poultry full of antibiotics to sustain the mass production of meat. The considerable quantities of antibiotics used in factory farming serve to inadvertently create resistance genes that can jump between bacteria-- resulting in the creation of drug-resistant strains that can infect humans.
Although antibiotic misuse is an important cause of antibiotic resistance, it is certainly not the only one. Superbugs are a significant threat not only due to bacteria evolving too quickly, but also because antibiotics are evolving too slowly. In the arms race between bacteria and antibacterial agents, the bacteria are winning. To say that the development of antibiotics is lagging would be an understatement-- the antibiotic pipeline is basically bone dry. Both the total number of antibiotics brought to market and the discovery of novel classes of antibiotics have declined precipitously in recent decades. The number of new antibiotics on the market has been declining since the 1980s and almost every currently available antibiotic is derived from a class discovered before the mid 1980s. When bacteria become resistant to antibacterial agents, they tend to be resistant to multiple agents in the same class. Without the development of new types of antibiotics with unique mechanisms of action, we don’t stand a fighting chance against drug-resistant organisms.
The WHO’s list of 12 superbugs published earlier this week classifies drug-resistant bacteria based on the urgency of developing antibacterial agents. This list is part of a global action plan and a call to spur the pharmaceutical industry to focus their efforts on the development of new essential antibiotics. One of the key reasons for the lack of progress in antibiotic development, is the retreat of the pharmaceutical industry en masse from antibiotic development. Of the 18 largest pharmaceutical companies, 15 had cancelled their antibacterial research & development programmes by the early 2000s. There is simply not a sustainable return on investment for antimicrobial drugs, compared with drugs for chronic conditions and cancer which can be sold for higher prices, have a larger market and are prescribed for a longer course than antibiotics. The abandonment of the antibiotic market by the leading pharmaceutical companies left academic institutions and smaller pharmaceutical companies with limited financial backing to bear the brunt of antibiotic development-- unfortunately with little success.
That is not to say that there is no hope. Upon recognizing the potential catastrophic consequences of inaction, governments, industry and international bodies have made steps towards combatting superbugs. Last year at the World Economic Forum, 85 companies in the pharmaceutical and biotechnology industries, signed the “Declaration on Combating Antimicrobial Resistance”, among these signatories were pharmaceutical giants such as AstraZeneca, GlaxoSmithKline and Pfizer. The declaration calls on governments to support R&D of antibiotics through incentivizing drug discovery. This global commitment is promising, and marks a recommitment of many major pharmaceutical companies to antibiotic R&D.
A lack of effective antibiotics to treat increasingly common infections will change medicine as we know it. The emergence of new superbugs and the rapid progression of bacterial antibiotic resistance can certainly be slowed by proper antibiotic stewardship. But a sustainable solution to the problem of antibiotic resistance must include the development of new antibiotics, including those in different drug classes with novel mechanisms of action. The lack of antibiotic alternatives can be explained by the pharmaceutical industry’s reticence to fund the development of new antibiotics. There must be a massive push from government and industry to revolutionize the antibiotic market through implementing financial incentives and regulatory policies that support antibiotic development. Without major changes in the drug development pipeline we will be powerless in the fight against superbugs.
Further Reading
https://www.scientificamerican.com/article/who-releases-list-of-worlds-most-dangerous-superbugs
https://www.scientificamerican.com/article/how-drug-resistant-bacteria-travel-from-the-farm-to-your-table/
http://www.pewtrusts.org/en/research-and-analysis/reports/2016/05/a-scientific-roadmap-for-antibiotic-discovery
https://academic.oup.com/cid/article/50/8/1081/449089/The-10-20-Initiative-Pursuing-a-Global-Commitment
https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cit070
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378521/
http://www.ifpma.org/partners-2/declaration-by-the-pharmaceutical-biotechnology-and-diagnostics-industries-on-combating-antimicrobial-resistance-amr/
http://apps.who.int/iris/bitstream/10665/193736/1/9789241509763_eng.pdf?ua=1
Written by: Emily Stephenson
Emily is currently in her first year of medical school at the Schulich School of Medicine and Dentistry and serves as UAEM Western's medical school liaison.
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