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

Antibiotics are hailed as medical preservatives.

But they’re facing a more insidious adversary: ​​bacteria mutate and adapt and outsmart drugs designed to defeat them and cure the infections they cause.

These antibiotic-resistant “superbugs” were directly responsible for 1.14 million deaths worldwide in 2021, according to The Lancet, a medical journal. Antibiotics – considered the first line of defense against severe infections – did not work in most of these cases.

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

But some hope is on the horizon. A number of promising new indigenously-developed drugs show potential to combat antibiotic-resistant pathogens. They also offer a game-changing solution to preserving last-resort treatment.

Enmetazobactam, developed by Chennai-based Orchid Pharma, is the first antimicrobial developed in India to be approved by the US Food and Drug Administration (FDA). This injectable drug treats acute conditions such as urinary tract infections (UTIs), pneumonia and bloodstream infections and targets bacterial defense mechanisms.

Bacteria produce enzymes such as beta-lactamase to destroy antibiotics. Enmetazobactam binds tightly to those enzymes, neutralizing them and allowing the antibiotic to effectively kill the bacteria.

Simply put, the drug immobilizes the bacteria’s “weapon” without easily provoking resistance. It also preserves the effectiveness of other antibiotics, including carbapenems, which are reliable “last line of defense” drugs.

Trials across 19 countries – the drug has been approved by global regulators – have shown its effectiveness in more than 1,000 patients. “The drug, which has evolved over the years, has shown remarkable potential against these bacteria. It is given by intravenous (IV) infusion in hospitals, particularly to critically ill patients, and is not available over the counter,” Dr Manish Pal, the drug’s lead co-researcher, told the BBC.

Mumbai-based Wockhardt is testing a new antibiotic called Zaynich for severe drug-resistant infections. The drug, which has been in development for 25 years, is currently in phase-3 trials and is expected to be released next year.

Owned by Dr Habib Khorakiwala, Founder Chairman of Wockard explained “This is a ground-breaking, new antibiotic of its kind designed to combat all major superbugs,” Zainich said. It was administered on a compassionate basis to 30 critically ill patients in India who had not responded to any other antibiotics. Remarkably, all survived. “It will make India proud,” said Dr Khorakiwala.

In phase-3 testing, Wockard’s nafithromycin, trademarked as MIQNAF, was a three-day oral treatment for community-acquired bacterial pneumonia with a 97% success rate. Resistance to existing treatments for the disease is as high as 60%. Its trials are due to conclude next year and once approved, it could be commercially launched by the end of next year, the company said.

A 30-member Bengaluru-based biopharma firm BugWorks Research has partnered with the Geneva-based non-profit Global Antibiotic Research and Development Partnership or GARDP to develop a new class of antibiotics to treat serious drug-resistant infections. In current phase-1 trials, the drug takes five to eight years from market readiness.

“Antibiotics are becoming less effective, but the big money is in drugs for cancer, diabetes and other conditions, not antibiotics,” Anand Anandakumar, CEO of BugWorks, told the BBC. “There is little innovation because antibiotics are kept as a last resort. Big medicine does not focus on antibiotic resistance. We have received funding from various institutions, but less than 10% of our funding has come from India.

But that needs to change. The Drug Resistance Surveillance Report 2023 by the Indian Council of Medical Research (ICMR), which analyzed nearly 100,000 bacterial cultures from 21 specialized care hospitals across India, highlighted an alarming trend in antibiotic resistance.

E.coli (Escherichia coli), commonly found in the intestines of humans and animals after ingestion of contaminated food, is the most frequently isolated pathogen.

This is followed by Klebsiella pneumoniae, which causes pneumonia and infects the blood, cuts in the skin and the lining of the brain causing meningitis. Closer is the rise of Acinetobacter baumannii, a multidrug-resistant pathogen that attacks the lungs of patients on life support in critical care units.

The survey found that antibiotic effectiveness against E.coli has steadily declined sharply, while Klebsiella pneumoniae has shown an alarming rise in drug resistance. Doctors have found that some of the main antibiotics are less than 15% effective in treating infections caused by these pathogens. Most worrisome is the increasing resistance to carbapenems, which are critical last-resort antibiotics.

“It’s like playing whack-a-mole with bacteria. They evolve incredibly fast and we’re always playing catch-up. You get rid of one, another pops up. We need more innovation and learning from past mistakes,” Dr Manika Balasegaram, executive director of GARDP, told the BBC. .

Not surprisingly, GARDP is focusing on India. It collaborates with Hyderabad-based Origin Pharmaceutical Services to produce zoliflodazine, a novel oral antibiotic for gonorrhea, a sexually transmitted disease showing increasing resistance to antibiotics. GARDP has partnered with Japanese pharma company Shionogi to distribute cefiderocol — an FDA-approved antibiotic for tough infections like UTIs and hospital-acquired pneumonia — in 135 countries, with plans to manufacture in India.

But this is only part of the story. Medicine prescription practices in India urgently need reform, say doctors. Widespread use of broad-spectrum antibiotics — which target many types of bacteria but kill good bacteria, can cause side-effects and increase antibiotic resistance — promotes drug resistance by promoting the emergence of drug-resistant bacterial mutants.

Instead, doctors say, narrow-spectrum antibiotics should be preferred. But hospitals often lack antibiotics — microbiology-based antibiotic guidelines — forcing doctors to prescribe “broadly and blindly.”

“I’m certainly excited that we have these new drugs. But what’s important is that we have to create mechanisms where we don’t misuse the (once) blockbuster drugs. Improper and irresponsible use will compromise the longevity of these new drugs,” warned ICMR scientist Dr. Kamini Walia.

The rapid transformation of bacteria that evolves within hours underscores the urgency of a holistic approach. These include reducing infections through better water, sanitation and hygiene, improving vaccine uptake, strengthening hospital infection control policies, educating doctors and preventing patient self-medication. “Combating antimicrobial resistance is a complex, multi-faceted challenge that is linked to health care equity and systemic accountability,” says Dr Walia.

The message is clear: without urgent action, we risk a future where even relatively minor infections are untreatable.