Published March 30, 2012
Some of modern medicine's most heralded interventions -- from routine surgeries to organ transplants and cancer treatments -- may soon be too dangerous. The viability of these procedures hinges on physicians' ability to use antibiotics to swiftly vanquish any bacterial infections that might arise in the course of treatment. For decades, physicians have been able to choose from hundreds of different kinds of antibiotics to do the job, including many powerful "broad spectrum" varieties that indiscriminately kill a wide range of bacteria. But over the past two decades, antibiotic drugs have started to fail one by one, as bacteria with resistance to them have emerged and spread. Taming the new drug-resistant pathogens requires ever more toxic, expensive, and time-consuming therapies, such as a class of last-resort antibiotics called carbapenems, which must be administered intravenously in hospitals. In the United States alone, fighting drug-resistant infections costs up to 8 million additional patient hospital days and up to $34 billion every year.
Now, the emergence in India of a particularly nasty form of antibiotic-resistant bacteria, which renders even the last-resort drugs obsolete, could bring about an era of unstoppable infections. To contain the bacteria, South Asian governments must quickly reform their public health practices and medical manufacturers must fast-track the development of new drugs. But with the Indian political establishment prioritizing building up its lucrative private health sector over making costly public health reforms, and policies aimed at recalibrating drug research and development in the West stymied, the political will to accomplish the job is scarce.
In India, antibiotic use is virtually unregulated. Antibiotics are widely available without a prescription and, as in the United States, affluent people tend to consume the drugs whether medically necessary or not -- for everything from colds to diarrhea. Meanwhile, when ill, India's poor tend to scrape together a few rupees to buy a couple doses of antibiotic at a time, enough to quell their symptoms but not enough to clear their infections. Both patterns of consumption contribute to the development of drug-resistant bacteria. So, it is no wonder that, even before the new super-resistant strain was first documented, over 50 percent of the bacterial infections that occurred in Indian hospitals were resistant to commonly used antibiotics.
Then, in 2010, a study of a New Delhi-area hospital found that 24 percent of bacterial infections there could resist the last-resort carbapenem antibiotics. Thirteen percent not only resisted carbapenem drugs, but overcame 14 other antibiotics, making treatment options exceedingly limited. The gene that conferred this extreme drug-resistance was dubbed "New Delhi metallo-beta-lactamase 1" or NDM-1. Scientists found that, unlike other drug-resistant bacteria, NDM-1 bacteria are able to quickly and prolifically spread their genes to other bacteria, easily jumping the barriers of species and genus. The pandemic potential of such a microbe is enormous. Indeed, according to Tim Walsh, a University of Cardiff medical microbiologist who has been chasing the dangerous gene, NDM-1 infections already turned up in more than 35 countries last year -- often in the bodies of medical tourists, who had traveled to India or Pakistan for cheap surgeries and other procedures. And NDM-1 bacteria have also been found in drinking water and in puddles around New Delhi.
Part of the problem in taming the bug is an ongoing failure to develop drugs to combat it. Despite growing global demand (and the World Health Organization's recognition that drug-resistant pathogens are one of the greatest threats to human health) the drug industry hasn't launched a new class of antibiotics to treat the class of bacteria susceptible to the NDM-1 gene in 45 years. As a result, there are only two imperfect drugs that can treat NDM-1 infections. The first, an antibiotic called colistin, was first sold over fifty years ago and fell into disuse in the 1980s, when less toxic drugs were developed using more modern methods. The second, tigecycline, is a pricey intravenous drug approved only for soft-tissue infections, not the urinary tract infections and pneumonias that comprise the majority of hospital-acquired infections. With more frequent use of these two limited drugs, it will be only a matter of time before NDM-1 bacteria can resist them as well.
According to the Infectious Diseases Society of America, the drug industry has actively avoided developing new antibiotics. This is a business decision: drugs that are prescribed for months and years, such as anti-arthritis or cholesterol-lowering drugs, and those for which patients and insurers will pay almost any sum, such as anti-cancer drugs, provide better return on investment. Antibiotics are costly to develop, only prescribed for a handful of days at a time, and, despite their curative powers, rarely fetch more than $100 per course. Further, all antibiotics eventually render themselves -- and the R&D investment behind them -- obsolete, since their use inevitably creates new drug-resistant pathogens. The United States and the EU have formed a task force on the issue, but as yet, no promising new drug is in the pipeline to treat NDM-1 bacteria. As a result, says Ramanan Laxminarayan, director of the Public Health Foundation of India, "places like India will just have to wait" as NDM-1 continues to evolve and spread.
Creating tomorrow's antibiotics is a huge challenge, but it is only half of the battle. Stanching the spread of NDM-1 and other drug-resistant bacteria will also require greatly improved stewardship of today's antibiotics: better surveillance of resistant strains, better control of infections in hospitals, and improved sanitation and hygiene. Here, Indian political priorities, and the country's haphazard sanitary infrastructure may prove disastrous.
In the wake of pro-market reforms in the early 1990s, India's economy has been expanding at a rate of 8 percent a year. But despite this growth, government spending on health hovers at around one percent of GDP a year, a proportion that critics condemn as far too low for a country with a prospering economy that is still heavily burdened by infectious disease. (Only Burundi, Cambodia, Myanmar, Pakistan, and Sudan spend proportionally less.) In India's finance-starved public hospitals, overcrowding is common and corruption rife. Nearly one-third of patients report having to resort to bribes just to get clean bed sheets. In most, says Laxminarayan, "you will find a person in the bed, another person under the bed, and one on the side of the bed." Patients' relatives, often the sole providers of nursing care, crouch on crumbling walkways outside hospital buildings under the blazing sun. The infamous open sewers of India's slums ooze nearby. These conditions are ripe for the rapid spread of pathogens, including NDM-1.
As the country's stunted public health infrastructure languishes, the private health sector has boomed. Encouraged by government tax exemptions, corporate hospital chains such as Apollo and Fortis, which are owned by large pharmaceutical and technology companies, dot the landscape, islands of apparent sterility amid the grime. Now, 80 percent of total Indian health expenditure goes to private clinics and hospitals. Besides caring for India's affluent, many of these hospitals market their upscale services to "medical tourists," patients from the UK, the United States, the Middle East, and elsewhere, who fly to India for procedures that are cheaper and quicker there than they would be home. It is a growth industry that brings in hundreds of thousands of foreign patients and over $300 million annually now, which is set to top $2 billion in coming years.
It was in the bodies of medical tourists who had traveled to India and Pakistan that the new super-resistant gene was first discovered by British scientists in 2009. But when those scientists named it "NDM-1," after the city from which it seemed to originate, and warned that other medical tourists might be at risk, Indian politicians, news media, and physicians cried foul, suggesting a conspiracy to undermine the medical tourism sector. India's National Centre for Disease Control spent days openly denying the public health relevance of NDM-1. Government authorities sent letters to Indian researchers who had collaborated with British scientists on the NDM-1 studies, demanding that they disavow their research. They also tried to prevent scientists from taking samples of NDM-1 out of India for research purposes.
Better nationwide surveillance of infectious pathogens could help target containment efforts, but here, too, capacity is limited. India's disease surveillance program collects information from only 2 of the country's 640 districts. Precious few hospitals have the well-equipped labs required to conduct microbiological sleuthing. Without convincing nationwide data, it's all too easy for politicians to dismiss reports about NDM-1 as the exaggerations of outsiders.
As the controversy over NDM-1 swirled, in 2011 New Delhi convened an advisory committee on the issue of antibiotic resistance which floated a proposal to ban the sale of antibiotics without a physician's prescription, and restrict the use of last-resort IV antibiotics to highly specialized hospitals. But after pharmacists went on strike in August 2011, the proposal was withdrawn. Experts say the move was nothing more than a gesture, in any case. The policy had little chance of being implemented and enforced: In India, health policy is implemented at the state level, not the federal level.
Nobody knows how many people may have already died from NDM-1 bacterial infections, nor how many more may sicken or die should the gene become more widespread. It may be that NDM-1 has to gain more notoriety and "get a lot more scary," as the Times of India put it last spring, before political will to do something about it coalesces. For now, experts such as Walsh estimate that NDM-1 bacteria silently lurk in the guts of up to 200 million people in India alone, evolving, exchanging genes with other bacteria, and being shed into the environment. In an interconnected world, they will not remain quarantined there for long.