AMU's Asadullah Khan checked water samples in the drains of the medical college and ended up discovering a new variant of New Delhi Metallo-betalactamse, called NDM-4
New Delhi: In January, a farmer living close to Aligarh Muslim University (AMU) was admitted at the university’s medical college with a seemingly simple kidney infection. Doctors at the J.N. Medical College, a tertiary care facility, were certain he would recover.
A week later, the patient’s infection had not responded to even the most powerful antibiotics. He died, leaving the doctors wondering about the extent of antibiotic resistance prevalent in the community.
The farmer’s death prompted Asadullah Khan, a scientist at AMU’s biotechnology department, to check the water samples in the drains of the medical college. He ended up discovering a new variant of New Delhi Metallo-betalactamse, called NDM-4—a superbug.
This was the first recorded presence of the deadly, drug-resistant strain in India that has so far been detected only in Cameroon, Denmark, France and the Czech Republic. NDM-4 is a more virulent form of the NDM-1 bacteria that was isolated in 2009 from a Swedish patient who contracted a bacterial infection in Delhi.
The identification and nomenclature became controversial, with India not taking kindly to a superbug being named after its capital city.
In fact New Delhi Metallo is simply an enzyme, and bacteria that carry it become resistant to most antibiotics. Worse, they can pass on this resilience to other bugs they come in touch with.
Antibiotic resistance is developed when microorganisms evolve and adapt to new drugs. When this happens, drugs that normally kill these organisms cannot treat the infection. A superbug is a bacteria that develops resistance to multiple antibiotics. The discovery of NDM-4 is ominous; the superbug is resistant to almost all known antibiotics, even the most powerful, last-resort antibiotics called carbapenems.
When it comes to antibiotic resistance, the scientific community has only two types of information—bad and worse.
First the bad news: as of now, carbapenems are the only treatment option for bacterial infections caused by bugs such as Escherichia coli (E. coli), responsible for such things as urinary tract infections, peritonitis, septicemia, and pulmonary complications. There are currently no new antibiotics in development to combat bacteria resistant to carbapenems, which makes discovery of these superbugs a potential nightmare scenario.
And it gets worse.
The Aligarh discovery cannot be dismissed as an isolated incident of a superbug discovered in a tier-II city of India. If superbugs can be found in sewage in smaller cities such as Aligarh, say scientists, it is almost certain that the problem is widespread across India.
“I can say with a fair degree of certainty that NDM-4 has spread in India," said Khan, whose study appeared in the September issue of the Journal of Medical Microbiology. The scientist is now trying to get funding for an India-wide study to assess the extent of the superbug’s presence.
India and a post-antibiotic era
Discovery of these superbugs in India is a cause for global concern. India has the largest number of patients treated for infectious diseases (including tuberculosis, malaria, filariasis, visceral leishmaniasis, leprosy, HIV and childhood cluster of vaccine-preventable diseases) which also means it has the most number of antibiotic users.
Then there is the sanitation angle—one reason why the importance of Prime Minister Narendra Modi’s ‘Clean India’ mission can’t be overemphasized.
Superbugs can be prevented from entering the human system through good hygiene. The bigger concern for India is the growing resistance of even bacteria that cause diseases such as tuberculosis to antibiotics. The World Health Organization (WHO) expects this resistant form of tuberculosis to affect 2 million people annually worldwide by 2015.
In India, particularly, where self-medication is common and drugs can be purchased over the counter without proper prescriptions, patients are more at risk to antibiotic resistance. Every time a patient pops an antibiotic for viral fever and does not finish the entire dosage, he/she allows the weaker virus/bacteria to survive the current line of treatment, thereby making it stronger.
“Easily treatable, mild illnesses are going to be the mass killers of the 21st century," said Narendra Saini, secretary general, Indian Medical Association (IMA).
In April, WHO released the first ever global report on antimicrobial resistance. Keiji Fukuda, assistant director-general for health security at WHO, said at the time: “Without urgent, coordinated action by many stakeholders, the world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill."
Since national data is not available, researchers conducted small surveys and found a staggering resistance in India for different classes of antibiotics. According to WHO, 61% Indians are resistant to third-generation cephalosporins; samples from the community and hospitals were 80% resistant to meticillin; and resistance to fluoroquinolones ranged between 82% to 11% in nearly six surveys conducted between 2003 and 2012.
The data in India is sketchy but the problem extends to the entire South Asia region, adds the report. “The report’s results show high levels of E. coli resistance to third generation cephalosporins and fluoroquinolones—two important and commonly used types of antibacterial medicine–in the region. Resistance to third generation cephalosporins in K. pneumoniae is also high and widespread. In some parts of the Region, more than one quarter of Staphylococcus aureus infections are reported to be methicillin-resistant, meaning that treatment with standard antibiotics does not work," the WHO report added.
The big challenge in India is poor regulation of prescription of medicines. “There is also a lack of knowledge among medical practitioners as well as the public on rational use of antibiotics. The health sector in India needs improved management of the health care delivery systems, both public and private, which will minimize conditions favourable for the development of drug resistance," the WHO report said. The emergence of resistance to artemisinin, used to treat malaria and multi-drug resistance in tuberculosis, is an especially “daunting" public health challenge not only for India but for South Asia, adds the report.
India’s health ministry has been particularly slow in its response to the growing threat of antibiotic resistance. While Khan is still struggling to get a multi-centered trial to investigate the penetration of NDM-4, the health ministry is mulling the need for a comprehensive study mapping the extent of the crisis.
“Antibiotic resistance is a growing concern," said V.M. Katoch, director general of the Indian Council of Medical Research. “We have created a task force to analyse the situation," he added.
The other steps the health ministry is considering include placing restrictions on the prescription of newer drugs as they become available in the markets. Regulating the older drugs will be a challenge, Katoch admitted.
“We cannot do this overnight. We are aware of the concerns in the public health community and this is a priority issue for the ministry as well. We are looking at ways to address the situation. We have started work on this front and are funding some studies to get original data at first," he added.
The Aligarh ailment
Meanwhile, Aligarh’s biggest hospital continues to receive patients who suffer from increasingly stubborn infections.
“There is just too much drug resistance in the community and obviously the cases in our hospital are becoming more and more challenging to treat," said Syed Hasan Harris, dean, faculty of medicine. “Since we are a tertiary care hospital, most of our patients have already been treated at some other facility before being referred to us. Neither do doctors know how to correctly prescribe antibiotics nor do patients know how to comply with the prescriptions. I can only say that our patients are antibiotic-resistant but exactly which microorganism they are resistant to will require further investigations," he added.
Harris says he doesn’t know how many patients have been affected by NDM-4 but adds that he has seen many patients with extended-spectrum beta-lactamases, enzymes that confer resistance to most antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam, adversely affecting treatment outcomes at the hospital.
IMA is holding Antibiotic Awareness week from 28 September to 4 October.
In 1945, Alexander Fleming, the man who discovered penicillin, stated in his Nobel Prize acceptance speech that “there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant".
The post-antibiotic era is not just an apocalyptic fantasy. No new classes of antibiotics have been discovered since 1987.
This is the first in a series on antibiotic resistance.
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