India’s ‘blockbuster’ drugs to combat antibiotic-resistant superbugs

Antibiotics are hailed as skilled saints.

But they are extremely confronted by a careless adversary: bacteria that develop, adapt, and outperform the very medications used to stop them and treat the infections they cause.

These antibiotic-resistant “superbugs” directly caused 1.14 million deaths worldwide in 2021, according to The Lancet, a medical journal. Antibiotics – which are considered to be the first line of defence against severe infections – did not work on most of these cases.

India is among the countries hardest hit by “antimicrobial resistance”. In 2019 alone, antibiotic-resistant infections caused around 300,000 deaths. They alone are responsible for the deaths of nearly 60,000 newborns each year.

But some promise is on the ocean. A number of appealing locally-developed innovative drugs show ability to combat antibiotic-resistant pathogens. They also offer a game-changing solution to keep last-resort solutions.

Enmetazobactam, developed by Chennai-based Orchid Pharma, is the first antimicrobial invented in India to be approved by the US Food and Drug Administration ( FDA ). This injectable drug targets bacteria’s defense mechanisms rather than the bacteria itself, treating severe conditions like urinary tract infections ( UTIs ), pneumonia, and bloodstream infections.

Bacteria often produce proteins, like beta-lactamase, to kill medications. Enmetazobactam essentially kills the bacteria by resolving its kinase with those enzymes, which the antibiotic then neutralizes.

To put it simply, the medicine immobilises the virus’s “weapon” without triggering weight quickly. This also preserves the effectiveness of various antibiotics, including cephalosporins, which are the reliable “last series of military” drugs.

Testing across 19 nations- the drug has been approved by international regulators- with more than 1, 000 patients have shown its success. The medicine has demonstrated extraordinary potency in treating these bacterial strains that have evolved over time. It is administered via intravenous]IV] injection in institutions, exclusively for critically ill patients, and is not available over the counter”, Dr Maneesh Paul, the prospect co-inventor of the medicine, told the BBC.

Mumbai-based Wockhardt is testing a fresh antibacterial, called Zaynich, for serious drug-resistant diseases. Developed over 25 years, the drug is now in Phase-3 testing and expected to launch next month.

Dr Habib Khorakiwala, founder chairman of Wockhardt, has described Zaynich as a “ground-breaking, one-of-its-kind new antibiotic designed to combat all major superbugs”. It was administered on compassionate grounds to 30 critically ill patients in India who were unresponsive to any other antibiotics. Remarkably, all survived. “This would make India proud,” Dr Khorakiwala said.

Also in Phase-3 testing is Wockhardt’s Nafithromycin, trademarked as MIQNAF, a three-day oral treatment for community-acquired bacterial pneumonia with a 97 % success rate. Existing solutions for the illness have tolerance levels of up to 60 %. The company claims that it could be competitively launched by the late end of the year when its studies are completed.

A 30-member Bengaluru-based biotech firm Bugworks Research has partnered with Geneva-based non-profit Global Antibiotic Research and Development Partnership, or GARDP, to create a new category of medicines for treating severe drug-resistant diseases. Now in early Phase-1 tests, the medicine is five-to-eight years from marketplace readiness.

“Antibiotics are becoming less effective, but big money is in drugs for cancer, diabetes and other conditions, not antibiotics,” Anand Anandkumar, CEO of Bugworks, told the BBC. “There’s little innovation because antibiotics are kept as a last-resort option. Big pharma isn’t focusing on antibiotic resistance. We’ve been funded by different organisations, but less than 10% of our funding comes from India.”

But that needs to alter. Concerning trends in antibiotic resistance were highlighted in a 2023 drug resistance surveillance report from the Indian Council of Medical Research ( ICMR), which looked at nearly 100 000 bacterial cultures from 21 specialized care hospitals throughout India.

The most frequently identified pathogen was E. coli ( Escherichia coli), which is found frequently in people’s and animals ‘ intestines after consuming contaminated food.

Klebsiella pneumoniae, which can cause asthma and even infects the heart, cuts in the epidermis and the brain’s lining, which can cause meningitis, followed by this. The multidrug-resistant disease Acinetobacter baumannii, which attacks patients on life aid in critical care units, was on the rise as well.

The survey revealed that Klebsiella pneumoniae showed an alarming increase in drug resistance while antibiotic usefulness against E. coli had constantly strongly decreased. Doctors discovered that some of the major medicines had less than 15 % success in preventing attacks brought on by these diseases. Most worrying was the rising resistance to carbapenems, a crucial last-resort antibiotic.

” It’s like playing whack-a-mole with bacteria. They evolve at an incredibly fast pace, and we’re constantly playing catch-up. You get rid of one, another pops up. We need more technology and to learn from history errors”, Dr Manica Balasegaram, senior director of GARDP, told the BBC.

No surprisingly, GARDP is focussing on India. It’s collaborating with Hyderabad-based Aurigene Pharmaceutical Services to create zoliflodacin, a book oral antibiotic for chlamydia, a sexually transmitted disease which is showing increasing resistance to antibiotics. In 135 countries, GARDP has established a partnership with Japan’s Shionogi to disperse cefiderocol, a revolutionary FDA-approved antibacterial for strong infections like hospital-acquired pneumonia, along with plans to make it available in India.

This is only the beginning of the narrative, though. Doctors claim that Indian drug prescribing practices desperately need to be changed. The widespread usage of broad-spectrum medicines, which target a wide range of bacteria but can eliminate fine bacteria, have negative effects, and increase antimicrobial resistance, fuels drug resistance by encouraging the development of drug resistant mutants.

Instead, say physicians, narrow-spectrum medications may become prioritised. But hospitals usually lack antibiograms- microbiology-based antimicrobial guidelines- forcing doctors to recommend “broadly and indiscriminately”.

” These novel medicines will certainly make me excited,” he said. However, it’s also crucial that we develop mechanisms to prevent them from being used in the same way as they have recently been with [what was again also] hit drugs. The durability of these new drugs may be hampered by poor and careless use, warns Dr. Kamini Walia, a scholar at ICMR.

The quick mutation of germs, which can develop in a matter of hours, underscores the necessity of a systematic approach. This includes reducing infection through better water, sanitation and hygiene, improving immunization adoption, strengthening hospital infection control laws, educating doctors and deterring self-medication by people. ” Combating antibiotic resistance is a complicated, multi-faceted problem tied to care equity and structural accountability”, says Dr Walia.

The message is clear: without immediate action, we risk a potential where yet relatively small infection had become intractable.