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

Antibiotics are hailed as medical saviors.

But they are increasingly facing a cunning adversary: ​​bacteria that mutate and adapt the very drugs designed to defeat them and treat the infections they cause.

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

India is among the countries most affected by “antimicrobial resistance”. In 2019 alone, antibiotic-resistant infections caused nearly 300,000 deaths. They alone account for almost all deaths. 60,000 newborns every year.

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

Enmetazobactam, developed by Chennai-based Orchid Pharma, is the first antibiotic invented in India to be approved by the US Food and Drug Administration (FDA). This injectable drug treats serious conditions such as urinary tract infections (UTIs), pneumonia and bloodstream infections by targeting the bacteria’s defense mechanisms rather than the bacteria themselves.

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

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

Trials in 19 countries – the drug has been approved by global regulators – have shown its effectiveness in more than 1,000 patients. “The drug has shown remarkable potency against bacteria that have evolved over the years. It is administered intravenously. [IV] infusion in hospitals, especially for critically ill patients, and is not available over the counter,” Dr Manish Pal, the drug’s lead co-inventor, told the BBC.

Mumbai-based Wockhardt is testing a new antibiotic, called Zaynich, for severe drug-resistant infections. Developed over 25 years, the drug is currently in Phase 3 trials and is expected to launch next year.

Dr. Habib Khorakiwala, Founder Chairman of Wockard described Zaynich as a “groundbreaking, first-of-its-kind antibiotic designed to combat all major superbugs”. It was given on a compassionate basis to 30 critically ill patients in India who were unresponsive to any other antibiotics. Remarkably, all survived. Dr. Khorkivala said, “This will make India proud.

Also in Phase 3 testing is Wockhardt’s Nafithromycin, trademarked MIQNAF, a three-day oral treatment for community-acquired bacterial pneumonia with a 97% success rate. Up to 60% are resistant to current treatments for the disease. Its trials are due to end next year and once approved, the company says it could be commercially launched by the end of next year.

BigWorks Research, a 30-member Bangalore-based biopharma firm, has partnered with the Geneva-based nonprofit Global Antibiotic Research and Development Partnership, or GARDP, to develop a new class of antibiotics to treat serious drug-resistant infections. can be prepared. Currently in early phase-1 trials, the drug is 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,” BigWorks CEO Anand Anand Kumar told the BBC. “There is little innovation because antibiotics are reserved as a last resort. Big Pharma isn’t paying attention to antibiotic resistance. We are funded by various organizations, but less than 10 percent of our funding comes from India.

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

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

This was followed by Klebsiella pneumoniae, which can cause pneumonia and infect the blood, skin, and lining of the brain, which can cause meningitis. Closer was the rise of a multidrug-resistant pathogen called Acinetobacter baumannii, which attacks the lungs of patients on life support in intensive care units.

The survey found that the effectiveness of antibiotics against E. coli has continued to decline rapidly, while drug resistance in Klebsiella pneumoniae has increased alarmingly. Doctors found that some important antibiotics are less than 15 percent effective in treating infections caused by these pathogens. Of greatest concern was the growing resistance to carbapenems, an important last-resort antibiotic.

“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. There is a need to innovate and learn from past mistakes,” GARDP executive director Dr Manika Balasigaram told the BBC.

Not surprisingly, GARDP is focusing on India. It is collaborating with Hyderabad-based Origin Pharmaceutical Services to develop zolifludacin, a novel oral antibiotic for gonorrhea, a sexually transmitted disease showing increasing resistance to antibiotics. has been GARDP has also partnered with Japanese pharma company Shionogi to distribute cefiderocol – an FDA-approved antibiotic for severe infections such as UTIs and hospital-acquired pneumonia – in 135 countries, with manufacturing in India. There are plans.

But that’s only part of the story. Doctors say there is an urgent need for reform in India’s drug prescribing practices. Widespread use of broad-spectrum antibiotics – they target many types of bacteria but can kill good bacteria, cause side effects and increase antibiotic resistance – drug-resistant bacterial mutants promote the emergence of drug resistance.

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

“I’m certainly excited that we’re going to have these new drugs. But what’s also important is that we have to create mechanisms so that they don’t get abused like we’ve done before. [what were once also] Blockbuster drugs. Improper and irresponsible use will compromise the longevity of these new drugs,” warned Dr Kaminiwalia, a scientist at ICMR.

The rapid turnover of bacteria, which can evolve in a matter of hours, underscores the urgent need for a holistic approach. This includes reducing infections through better water, sanitation and hygiene, improving vaccine uptake, strengthening hospital infection control policies, educating doctors and preventing patients from self-medicating. “Combating antimicrobial resistance is a complex, multifaceted challenge that is tied 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 may become untreatable.