The crisis of antimicrobial resistance in India

Most antibiotics are half a century old and the overuse of these drugs has created an acute antimicrobial resistance (AMR) crisis worldwide which is claiming a large number of lives, including in India.

A recently published study in The Lancet, examined 471 million individual patient records, reviewing medical literature, hospital and surveillance systems and used predictive statistical modelling to produce estimates of the AMR burden for all locations, even places with little data. Researchers found that there were an estimated 4.95 million deaths associated with bacterial AMR in 2019 alone, including 1.27 million deaths attributable to bacterial AMR.

The researchers wrote, “Our estimates indicate that bacterial AMR is a health problem whose magnitude is at least as large as major diseases such as HIV and malaria, and even potentially much larger. Bacterial AMR is a problem in all regions. We estimated that in 2019, the highest rates of AMR burden were in sub-Saharan Africa.”

However, India does not fare much better. The paper detailed five pathogens that were defeating some of the most effective antibiotics in the country. This includes Staphylococcus aureus which is defeating Methicillin, Mycobacterium tuberculosis which is thwarting Isoniazid and Rifampicin, Escherichia coli which is not only beating a third-generation drug Cephalosporins but also Flouriquine, Acinetobacter baumannii which is resistant to Carbapenem and Klebsiella pneumoniae which is resistant to both Carbapenem and third-generation Cephalosporin.

Worldwide, one pathogen-drug combination, methicillin-resistant S aureus caused more than one lakh deaths and drug-resistant tuberculosis, E coli, A baumannii, K pneumoniae caused between 50,000 to one lakh deaths annually.

For Dr Neha Mishra, an infectious diseases expert, this comes as little surprise as she has regularly catalogued AMR cases, which she says have increased dramatically in the last decade. “Some 70% of the cases that we get have a degree of AMR. One pathogen, the Klebsiella pneumoniae bacteria, is completely resistant to one of the best antibiotics we have: Carbapenem,” she said.

But as comprehensive as the Lancet paper is, it covers data only until 2019. The onset of the Covid-19 pandemic and widespread use of antibiotics especially in the first and second waves, has dramatically worsened the situation, experts believe.

AMR accelerated

“The pandemic has accelerated AMR because of the widespread consumption of antibiotics during the various waves,” said Dr Santanu Datta, Chief Science Officer of Bugworks, an Indian startup that has achieved the remarkable — germination of new dual-targeting broad spectrum antibacterial agents that is currently under Phase 1 clinical trials in Australia.

However, just how big the AMR problem is not yet known although studies are underway in various parts of the world to readjust AMR incidence rates due to the pandemic. “Whatever AMR cases are reported as a result of the pandemic are just the tip of the iceberg,” Dr Mishra said.

Although the Indian Council for Medical Research removed antibiotics from the recommended treatment list, many fear-struck people continue to ingest antibiotics when they are diagnosed with Covid-19.

“In my prescriptions for Covid-19 patients, there is only Dolo, vitamins and Zinc. But patients sometimes go on to purchase antibiotics anyway because of fear of the disease. Even for the smallest of complaints, the antibiotic, azithromycin, was used,” Dr Mishra said.

The effect of the pandemic is a particularly thorny addition to India’s AMR problem which is already beyond the point of no return. “We are at a point where AMR can only be treated by a new generation of antibiotics,” Dr Datta said.

The matter is serious enough for scientists across India to work together on solutions. At the Centre for Cellular and Molecular Platforms (C-Camp) which is part of Bangalore Life Sciences Cluster (along with the National Centre for Biological Sciences), a raft of startups have been hard at work, trying to develop diagnostic and therapeutic solutions to tackle AMR. Among them is Dr Datta’s Bugworks.

Dr Taslimarif Saiyed, CEO and Director of C-Camp, said that the centre has been actively seeking to address AMR for the last five to six years.

Unregulated use

“Susceptibility to AMR is driven by the widespread use of broad-spectrum antibiotics among the general public in India. Illnesses in India are addressed by a person going to a doctor or to a pharmacy to obtain broad-spectrum antibiotics without there having been an attempt to find what infection is causing the fever,” he explained.

“Ideally, blood tests or urine tests are needed to determine the cause of the infection which normally takes two days to return a result. Not all antibiotics are useful against a particular infection— so these tests are necessary to determine which particular antibiotic needs to be used. Instead, there is a widespread use of broad-spectrum drugs which causes an extreme reaction in a person,” he added.

As per publicly available data, India is the highest user of antibiotics in Southeast Asia and is among the top users worldwide — a standing driven by rampant over-the-counter sales, plus extensive use of antibiotics in the animal meat market.

Experts said that antibiotics are widely injected into animals reared for human consumption such as chicken, pig, lamb and cows. “Antibiotics cause the development of more fat and causes the meat to become tastier and also induces lethargy in the animals,” Dr Datta said.

“While EU is cutting down the antibiotics in their meat industry, antibiotics overuse is prevalent in poultry farms in India. A person in India ingests as much antibiotics from animal meat as they would from sustained ingestion of tablets,” he added.

The result is that the scale of AMR is higher in India than in other countries — 60 to 80% of medical cases have a degree of AMR. This results in a range of serious medical complications.

Dr Datta explained, “If the bacteria gets into the blood there are severe implications. Blood happens to be a fantastic medium for bacterial growth. In the case of most elderly deaths, the last stage is septicemia for which there is little hope of treating because of AMR. If AMR was not so prevalent in India, nearly 30-40% of the people who died of Covid-19 could have been saved,” he added.