Antibiotic resistance, also known as antimicrobial resistance (AMR), is both a widely recognised threat and a frightening reality. Much like global warming, the evidence for AMR has been around for a long time – knowledge of AMR actually predates the clinical introduction of penicillin in 1943 – but has only recently entered the public consciousness as we stand at the precipice of a global crisis.
It is worth restating the transformative impact that antibiotics have had; the many millions of lives saved since the discovery of penicillin by Alexander Fleming in 1928. In countries where sanitation is poor, antibiotics play a crucial role in preventing infections from contaminated water and limited hygiene. In our healthcare system, being able to treat bacterial infections has made surgery incredibly more safe and managing chronic diseases incredibly more successful. Antibiotics are among the major factors in the extended lifespan we enjoy when compared to previous generations.
Bacteria develop resistance to antibiotics as a result of evolution. A random genetic mutation that confers resistance to antibiotics spreads rapidly through the population (those without this mutation are killed by the antibiotic, as intended) and eventually leads to an entirely resistant population. However, it’s not the whole story. Bacteria have mobile genetic elements – known as plasmids – that allow horizontal gene transfer. Genes are transferred not just to the bacterium’s progeny but also to their neighbours, even if those neighbours happen to be from different species. The video below shows how bacteria can acquire resistance to 1000x the starting lethal concentration of antibiotic in just 11 days. Darwin would marvel at such an effective example of evolution by natural selection.
No past or present antibiotic appears to be immune – hopes were high for vancomycin when it was introduced in 1972 to treat methicillin resistant Staphylococcus aureus (it had been extremely difficult to induce resistance in the lab). The first cases of vancomycin resistance were reported in 1979.
The pharmaceutical industry’s response to the menacing spectre of resistant bacteria was, admirably, to keep developing new antibiotics. The timeline below shows the battle between bacteria and science; science is losing. As the NHS’ Chief Medical Officer acknowledges here in a brilliant lecture, the last drug has fallen. Researchers identified a gene in 2016 – mcr1– that confers resistance to colistin which is only used when other antibiotics have proven ineffective, due to resistance.
Antibiotic resistant infections now claim around half a million lives a year worldwide, including 25,000 lives in Europe. Diseases previously thought to have been eradicated are making a comeback. For example, in 2014, there were 126 cases of tuberculosis in London that were resistant to at least one antibiotic.
AMR is frightening. Going back to medicine in the pre-antibiotic era would be catastrophic. This is why a paper published last week generated a huge deal of excitement. It described a new antibiotic derived from naturally occurring arylomycins that block a protein on the bacterial membrane which is essential for survival, known as SPase. The new compound has shown efficacy treating some of the most dangerous multidrug-resistant Gram-negative bacteria including Escherichia coli and K. pneumoniae. The complicated graph below shows the results of using this new antibiotic in mice infected with different pathogens – after treatment at certain dosages the bacterial burden (the number of bacteria present) has decreased significantly.
As exciting and encouraging as new antibiotics are, they form only a part of the answer. Overuse and misuse of antibiotics allow bacteria to develop resistance much more quickly. Consequently, as a government report recently highlighted, several drastic changes are required including a significant reduction in the use of antibiotics, in both medicine and agriculture, alongside huge investment in new diagnostic tools, vaccines (to prevent the need for antibiotics) and improving sanitation and hygiene. If not, scientists developing new drugs like the one above will be fighting a losing battle.