Dr Alexander Fleming, the bacteriologist who won the Nobel Prize for discovering penicillin, warned in his prize lecture that the misuse of antimicrobials may someday lead to microbes being ‘educated to resist’ antibiotics such as penicillin.Fast forward roughly a century and India is at the epicentre of a pandemic of drug-resistant infections. Decades of easy availability and misuse of antimicrobials has led to the emergence of drug-resistant strains of common pathogens like diarrhoea-causing E coli.
India reported the world’s highest burden of extensively drug-resistant tuberculosis (XDR-TB) in 2017. Not only are strains of XDR-TB resistant to the primary treatments for tuberculosis, they are also resistant to several of the fallback treatments. This means they are more expensive to treat, the side-effects of treatment are typically more severe and mortality rates are significantly higher.
Patients develop drug-resistant infections either through misuse of drugs or by catching the infection from someone who is infected with such a strain. Misuse can be a function of both underuse and overuse. Exposing pathogens to insufficient doses of antimicrobials encourages resistance development, so doctors and patients who are not careful about dosage or completing their courses may inadvertently incubate superbugs.
To put it crudely, what doesn’t kill the bugs often makes them stronger. Overuse is due to the combined problems of easy access and over-prescription, the latter often occurring when irresponsible or unaware doctors and pharmacists write unnecessary prescriptions. For instance, patients are routinely prescribed antibiotics (effective only against bacterial infections) for viral infections such as colds and flus.
Once superbugs are created, the challenge becomes containing them. Densely populated areas with poor sanitation and inadequate healthcare infrastructure are therefore especially vulnerable to vicious circles of delayed diagnosis, spread of infections, inappropriate treatment leading to high levels of resistance in local microbe populations and so on. It’s perhaps no surprise that a disproportionate number of XDR-TB cases are reported from cities like Mumbai, where more than 40% of the population lives in slums.
India’s contribution to this crisis has recently been documented in the naming of the gene NDLM-1 or New Delhi metallo-beta-lactamase 1. This gene was first noticed in patients from India. It renders bacteria resistant to carbapenems, a category of strong antibiotics that are commonly referred to as drugs of last resort. In theory, such drugs should be reserved for situations in which other treatments have failed. In practice, poor awareness and control means that these drugs are often used in the first instance. Failure to ‘conserve’ these drugs of last resort means that we may have no way of treating infections caused by bacteria which manage to develop a resistance to them.
It also doesn’t help that new antibiotics are difficult to develop—only two new classes have been developed in the past 50 years. The pharmaceutical industry is reluctant to invest in drugs like antibiotics due to the low prices of generics, the potentially short shelf-life before microbes develop a resistance and the fact that such drugs are taken for short periods (as opposed to medication for chronic conditions such as diabetes).
The Indian government released a comprehensive National Action Plan on Antimicrobial Resistance (NAP-AMR) in 2017, but commitment has been patchy. The 2017-2018 Budget allocated only `1.16 crore to countering AMR while the 2018 Budget didn’t allocate any dedicated funds at all. Instead, funds for AMR were part of a common pool alongside a range of other public health programs. As of September 2019, Kerala and Madhya Pradesh were the only states that had developed and notified action plans.
Although the NAP is comprehensive, it will have to be implemented through sustained efforts across multiple fronts. For starters, prescription and dispensation need to be controlled more effectively across hospitals, nursing homes, clinics and pharmacies. Awareness among the medical community must be strengthened, right from emphasising responsible prescription in medical school syllabi to investing in continuing medical education for practising clinicians.
Rampant overuse in agriculture must be addressed on priority as India is the world’s fourth-largest consumer of veterinary antibiotics. Drug-resistant bacteria have been known to infect humans through contact with live animals or through consumption of animal products such as meat and eggs. Focusing on sanitation and hygiene in high-density zones like slums is also crucial to limiting the spread of resistant bugs. Lastly, the government must encourage investment into R&D for new antimicrobials.
Fleming noted in the 1920s that it was ‘not difficult’ to make microbes resistant to antibiotics. The first 100 years of the antibiotic era have confirmed this. What remains to be seen is whether this trend can be reversed so that we’re not facing the prospect of a post-antibiotic era where routine infections are once again lethal.