Drug-resistant infections: How we got here and what the future holds Published: 5 February 2020 By Kish Adoni, Research and Membership Intern, AMRC “We really are facing, if we don’t take action now, a dreadful post-antibiotic apocalypse”. You could be forgiven for thinking that this formed the narrative arc of a cheap disaster film but these are, in fact, the words of Dame Sally Davies in 2011, when she was Britain’s Chief Medical Officer. By 2050, drug-resistant infections are expected to claim 10 million lives each year, crippling the economy to the depths of the 2008 financial crisis. Why are drug-resistant infections such a threat? The impact of antibiotics on society cannot be overstated. I’d like to take you back to the world pre-antibiotics, to the 13th century when the bubonic plague killed one third of Europe’s population (over 300 million people) in just three years! Skip ahead to that fateful morning in 1928 when Alexander Fleming returned from his two-week vacation to discover mold on a Staphylococcus culture plate; its implications were as impactful as just about any discovery by humanity before or since. The chemical secreted by his bacteria was penicillin, and in 1942 it was administered as an antibiotic medication for the first time. Penicillin alone went on to save roughly 200 million lives. If you need any more persuasion over the influence of antibiotics, you are hard to impress, but I can keep going! This medical marvel has underpinned multiple life-changing procedures including chemotherapy, organ transplants, joint replacements and cardiac surgery as well as treatments for chronic diseases such as diabetes, renal disease and arthritis. But what if these advances were to be banished from the fabric of medicine? It would be like pulling a rug from under the foundations of the healthcare industry! Returning to Davies’ warning, a post-antibiotic apocalypse is no longer as absurd as one would initially think. How did we get here? Early cautions of drug-resistant infections from the likes of Fleming fell on deaf ears, as penicillin and streptomycin of the 40’s were supplemented by broad spectrum tetracycline and chloramphenicol in the 50’s. The pharmaceutical industry believed that they could stay ahead in the microbial arms race, facilitating over-prescription of antibiotics by clinicians around the world. By the 60’s evidence of the transfer of resistance genes across bacterial strains and species had come to light. Reports started to emerge on the spread of drug-resistant diseases from animals to humans, aided by the widespread use of antibiotics in livestock. News of these ‘superbugs’ hit the mainstream media in 1966 but little was done to combat drug-resistant infections. The continued over-use of antibiotics has cultivated a society where infectious diseases are no longer as responsive to antibiotics as they once were. The number of common Staphylococcus aureus infections resistant to penicillin has dramatically increased from 13% to 91%. Soon many of our antibiotics will become ineffective. Each year we see drug-resistant infections claim 700,000 lives and yet, rather alarmingly, since the 80’s, no new classes of antibiotics have been introduced to market. Why are there no new classes of antibiotics? In short, it’s not economically viable. Antibiotics are curative, with short periods over which a course is completed. This doesn’t lend well to profits. A cost-benefit analysis by the London Office of Health Economics calculated that a novel antibiotic is worth roughly $50 million, compared to $1 billion for a new drug that treats a chronic disease. To add to this, due to campaigning against the over-prescription of antibiotics, clinicians tend to hold new drugs as a last line of defense, instead preferring older antibiotics that have a comparable efficacy. Resistance has eventually been documented in nearly every antibiotic on the market. Consequently, by 2013, 15 of the 18 largest pharmaceutical companies had abandoned the antibiotic field. Is it all bad news, or is there some hope for the future? So far, it all looks pretty bleak, but a combination of recent campaigning and research breakthrough’s give cause for optimism. Today, the World Health Organisation calls for “a coordinated, multisectoral ‘One Health’ approach”, recognising that human, animal, food and environmental health are closely interconnected across the globe. To complement this, microbial labs are now armed with the whole genome of over 30,000 microbial strains, transcriptomics, proteomics and plenty of other novel technologies. This has revealed a myriad of biochemical information which can be used to combat drug-resistant infections. Medical research charities are also a source of hop. 15 of our members provide vital funding for drug-resistant infection research in the UK and overseas including drug repurposing, developing new antibiotics and designing biofilm blockers. This isn't the only way they're making a difference. They play a vital role in influencing global policies and practice: building governance frameworks, creating a portfolio of open research and data to guide strategies, and facilitating faster clinical trials through global clinical trial networks. We will continue to do our part to support the sector in stemming the rise and spread of drug-resistant infections. We must all work together if we are to save the lives of millions and safeguard the medical progress of the past hundred years for future generations.