Can antibiotic apocalypse be avoided?
Researchers from several Chinese, British and US universities announced that they have identified a new form of resistance, to colistin. They say they first perceived a colistin-resistant E. coli in 2013, in a pig from an intensive farm near Shanghai, and then noted increasing colistin resistance over several years.
Colistin is a last-resort antibiotic used when all others fail.
It has been introduced in 1959 but has not seen widespread use in humans because it causes kidney damage. And precisely because it has not been used much, bacteria have not developed resistance to it until now. On the other hand, colistin is cheap and is therefore an affordable addition to animal feed, to make animals put on muscle mass faster, and protect them from the conditions of intensive farming.
Europe has banned the use of antibiotics to boost the growth of livestock as it can contribute to resistance. China is one of the world’s highest users of colistin in agriculture. The global demand for that antibiotic in farming is expected to reach 11 942 tonnes a year by the end of 2015.
The resistance to colistin is due to the MCR-1 gene which is contained on a plasmid. This enables transfer of the resistance DNA between bacterial species, and its rapid movement around the globe. The rapid dissemination of previous resistance mechanisms (e. g., NDM-1) indicates that, with the advent of transmissible colistin resistance, progression of Enterobacteriaceae from extensive drug resistance to pan-drug resistance is inevitable and will ultimately become global. NDM-1 is thought to have emerged in India but due to international travel, cases have been detected around the world. Enterobacteriaceae are now the most common form of hospital acquired infection. Opportunistic infections – those that often hit the elderly when they are already ill and vulnerable in hospital – are one of the main concerns.
However, not every such prediction comes true. In the early 2000s, physicians were very alarmed when resistance to vancomycin— another last-resort antibiotic preserved from the 1950s—moved via a plasmid from Enterococcus into Staphylococcus aureus. At the time, people were already worried about the better-known form of drug-resistant Staphylococcus, MRSA; the emergence of VRSA, as it became known, raised even more concerns. In the end, though, there have been only 14 such infections in the United States over a period of 15 years.
But what makes the new colistin resistance different from VRSA is the role that agriculture seems to be playing in its evolution and dispersal: First, thousands to millions of animals are getting the drug, which exponentially expands the opportunities that favor resistance. And second, projects such as the Chinese one that allowed the new gene to be discovered are rare—so colistin resistance could begin moving, from animals and into people, without being noticed. In fact, while the authors were preparing their publication, the European Molecular Biology Laboratory received five submissions of bacterial data that appeared to contain the MCR gene—but from Malaysia, not China.
About 25,000 patients a year die in the European Union from an infection caused by a bacterium that is resistant to more than one antibiotic – and on current trends this is predicted to grow to 390,000 a year by 2050. “It’s a pretty grim future, I think a lot of major surgery would be seriously threatened,” said Prof. Richard James from the University of Nottingham. The rise in antibiotic resistance is being compared to the threat of global warming.
This picture shows the “treatment” of tuberculosis with fresh air in 1932. In the pre-antibiotic era, whether a patient would survive or not, has been a matter of luck.
According to Prof. Neil Woodford from UK’s Health Protection Agency, the worst case scenario would “be like the world in the 1920s and 30s – you could be gardening and prick your finger on a rose bush, get a bacterial infection and go into hospital and doctors can’t do anything to save your life. You live or die based on chance”.
The antibiotic discovery process is now in terminal decline. From the 1930s to 1970s, at least 11 new classes of antibiotics were discovered; since then there have been only two new classes.
Many antibiotics today are “broad spectrum” – they kill a broad range of bacterial species. The unfortunate side effect is that, along with the disease-causing bacteria, many other bacteria in the patient’s intestines are also killed. This puts the treated patient at risk of a more severe infection.
A significant ray of hope might come from bacteriocins – protein antibiotics produced by bacteria to kill closely related species, and therefore narrow-spectrum ones. Although injecting a “foreign” bacterial protein into a patient is likely to induce a severe immune response that would make the antibiotic inactive, data presented from animal studies show this was not the case. Several bacteriocin-derived antibiotics (BDAs) have already been designed to kill target bacteria, fungi and even tumor cells. By combining the targeting and killing domains of bacteriocins, hundreds of different hybrid proteins can be made.
There is a need to improve the economic incentives for the development of antibiotics. Some people have even suggested that antibiotics need to be far more expensive – something more like the price of new cancer drugs – in order for them to be used appropriately. The 2015 Review on Antimicrobial Resistance called for an innovation fund of $2bn over five years, funded by the pharmaceutical industry. The fund would guarantee a return on private companies’ investment if they produced an antibiotic that filled an unmet need. This proposal is aimed to achieve the development of 15 new antibiotics in a decade.
