In April 2011, the World Health Organization (WHO) warned that indiscriminate use of antibiotics was giving rise to resistant ‘superbugs’ which could render the drugs useless. Three years later, it warned about the arrival of a ‘post-antibiotic era.’ In autumn 2014, US officials termed antibiotic resistance a threat to national security.
However, awareness of this challenge has been present for decades. In the early 1990s, ‘Newsweek’ dramatically highlighted the threat in a cover story titled ‘End of the Miracle Drugs.’ A few months later, ‘Time’ magazine followed up with a feature on the ‘Revenge of the Killer Microbes.’
Bug resistance too knows no frontiers
The Centers for Disease Control and Prevention (CDC) has estimated that resistant bacteria lead to 23,000 deaths in the US every year. In Europe, the ‘British Medical Journal’ has urged authorities to harmonize antibiotic prescribing practices in order to tackle resistance. In spite of little effect on patients’ recovery times, an EU-funded study called GRACE identified wide variations in antibiotic use. For coughs, for example, antibiotic prescribing by physicians ranged from 20% in some countries to 90% in others.
Nevertheless, according to a report in the ‘The New York Times’ at the end of 2014, efforts to crack down on “inappropriate antibiotic use in the United States and much of Europe have been successful,” with prescriptions dropping from 2000 to 2010. Such a drop has, however, been “more than offset” by growing use in the developing world, according to ‘The Times’.
Indeed, like bugs themselves, drug-resistant bugs seem to know no frontiers.
Large emerging markets drive global drug sales
The ‘Times’ reports that sales of antibiotics for human consumption worldwide rose by 36% in the 2000-2010 period, with more than three-fourths of this increase accounted by the BRICS group of major emerging markets (Brazil, Russia, India, China and South Africa).
Such findings have been endorsed by an authoritative study, published in September 2015 by the Center for Disease Dynamics, Economics and Policy (CDDEP). The CDDEP report, which has drawn up a global Resistance Map for antibiotics, found sharp growth in resistant bacteria in developing countries, notwithstanding much lower per capita use of antibiotics.
India: highest risk case
The respected journal ‘New Scientist’ has recently also covered the CDDEP report, singling out culprits as countries with growing wealth – “especially India,”… “where more people are demanding antibiotics for minor infections.”
Indeed, the CDDEP highlights the case of E. coli in contaminated water or food, where India shows the world’s highest rates of resistance to nearly every available drug. Other problems in India include MRSA, where isolates have shown prevalence rising sharply, from 29% in 2009 to 47% in 2014 and Klebsiella pneumoniae, which can cause fatal lung infections. In 2014, 57 per cent of Klebsiella pneumoniae samples tested in India were resistant to carbapenems, an antibiotic used as a last resort. By comparison, the figure six years ago was virtually zero.
Resistant bacteria and infants
Antibiotic resistance has an especially dramatic impact on Indian infants. According to the ‘New York Times’ article in December 2014, bacterial infections resistant to most known antibiotics led to the death of more than 58,000 newborns in India compared to the previous year. The head of Sir Ganga Ram Hospital, one of India’s top medical facilities, stated that such infections were unheard of just five years previously. “Now, close to 100 percent of the babies referred to us have multi-drug resistant infections,” he lamented.
Ironically, due to high rates of infant mortality, the Indian government has been encouraging women, sometimes with financial incentives, to deliver babies in hospitals. The programme seems to have worked. Within a decade, the share of babies born in hospitals has more than doubled to over 80%.
However, the government has spent little to increase hospital capacity. As a result, maternity wards are overcrowded, sometimes with two or three women per bed. Apart from overcrowding, many hospitals are unhygienic. A UNICEF survey of 94 district hospitals and health centres in the Indian state of Rajasthan found 78% lacked soap at hand-washing sinks, while 67% of toilets were unsanitary.
The impact of bacterial resistance is, however, not just confined to newborns. Resistant bacteria cost the life of Uppalapu Shrinivas, one of India’s most famous musicians, at the age of 45.
Indeed, according to Dr. Timothy R. Walsh, a professor of microbiology at Cardiff University, India is creating a “tsunami of antibiotic resistance that is reaching just about every country in the world.”
NDM1: New Delhi’s global export
Researchers have already tracked superbugs with the so-called NDM1 (New Delhi metallo-beta lactamase 1) genetic code, first identified in India. NDM1 makes bacteria resistant to almost all antibiotics, including carbapenems – the drug of last resort.
The first report about NDM1 was published in ‘Lancet Infectious Diseases’ in April 2011, and made headlines due to the fact that this was the same time when the World Health Organization warned about superbugs.
The ‘Lancet’ study was sponsored by the EU and reported that NDM1 was found in about one fourth of water samples in New Delhi, the Indian capital. The authors speculated that, since many Americans and Europeans travelled to India and Pakistan for elective medical procedures, it was likely the superbug gene could eventually spread worldwide.
Since then, NDM1 has been found in Europe, the Middle East, Japan and the United States.
Meanwhile, back in India, what worries public health experts is “that the NDM 1 gene appears to have spread to germs that cause cholera and dysentery, two common and dangerous ailments in India.” In other words, it may be no exaggeration to say that the drug resistance problem is about to explode.
From toilet deficits to untreated sewage
The roots of the problem are complex. Bacteria spread relatively easily in India, since an estimated half of Indians defecate outdoors. Meanwhile, much of the sewage generated by the other half, who use toilets, is also left untreated. The result is expected: Indians have some of the world’s highest rates of bacterial infections – and resistance.
Cardiff University microbiologist Dr. Walsh says up to “95% of adults in India and Pakistan” carry bacteria that are resistant to ‘last-resort’ antibiotics such as carbapenems. By comparison, only 10% of adults in the Queens area of New York carry such bacteria.
The answer to no sanitation: use antibiotics, preventively
Ironically again, rather than building better infrastructure for sanitation, the response in India to growing bacterial infections has been to resort indiscriminately to antibiotics, which are often sold without a prescription. According to the December 2014 report in ‘The New York Times’, Indians collectively take more antibiotics than any other group of people.
Together, the lack of sanitation and overcrowding in hospitals may well have catalysed the superbugs. Doctors across India too have lent the crucial helping hand by responding to the hospital sanitation crisis through doling out antibiotics. In the Indian State of Haryana, for example, almost every baby born in hospitals in recent years has been injected with antibiotics – “whether they showed signs of illness or not,” Dr. Suresh Dalpat, deputy director of child health told ‘The New York Times’.
Completing the circle is the fact that the resistant bacteria, created by indiscriminate use of antibiotics, find their way into hospital sewage. As mentioned, much of this is untreated and dumped into canals and pits in nearby communities, leading to the infection of pregnant women, the delivery of ill infants – and more antibiotics.
A perfect storm
Though some Indian health experts believe drug-resistant bacteria to be largely confined to hospitals, some of India’s top neonatologists suspect the bacteria have begun “thriving in communities and even pregnant women’s bodies.”
“India has a perfect storm,” says Dr. Ramanan Laxminarayan, author of the CDDEP report. “You put all the things together and it’s this gigantic petri dish of experimentation that is resulting in highly pathogenic strains.”
Nevertheless, rushing to blame India alone (or India and other developing nations) for the growing drug resistance may not be helpful, or entirely accurate. Carbapenemases like NDM-1 have also been discovered elsewhere. For example, Klebsiella pneumoniae carbapenemase (KPC), currently the most common carbapenemase, was detected in the US in 1996 and has since spread worldwide. In addition, enterobacteriaceae which produce KPC have recently been reported as becoming common in the US.
Drug industry in India adds to the problem
In India, nevertheless, yet another growing area of concern seems to be loose compliance with regulations by Indian manufacturers of antibiotics. In early 2011, ‘Scientific American’ reported high levels of antibiotic resistance in bacteria downstream from a waste-water treatment plant in the southern Indian State of Andhra Pradesh.
Citing findings by a Swedish-led research team, the article noted that drugs in the effluent water from the plant were “sometimes equivalent to the high doses that are given therapeutically.” The antibiotic-rich water originated from the plants of 90 bulk drug manufacturers in the region.
The next wave: animal antibiotics in India
The other area for attention does not concern human use of antibiotics. Their overuse in chicken, pig and cattle farms in the US has also provoked the growth of resistant strains. Research has not only shown that “as much as half of antibiotic prescriptions in the United States are unnecessary,” but also that an estimated 80 percent of antibiotic sales remain directed at animals.
In Europe, unlike the US, antibiotics for animal growth have been banned since 2006. However, their use in medicated feeds continues. This, in turn, fuels resistance to antibiotics, and not just through animals. One study in Poland discovered high levels of resistant bacteria in gardens, orchards and forest soils, largely due to manure from antibiotic-fed animals.
Unfortunately, India does not seem to be heeding such lessons. Its booming economy has led to rapid growth of industrialized animal husbandry, where antibiotic use is widespread. A science group in New Delhi found antibiotic residues in 40 percent of chicken samples.