India’s ‘blockbuster’ drug to fight antibiotic-resistant superbugs

Antibiotics are recommended as medical saviors.

But they are increasingly facing an insidious enemy: viruses that change and adapt and defeat the very drugs designed to defeat them and treat the diseases they cause.

These antibiotic-resistant “superbugs” are directly responsible for 1.14 million deaths worldwide by 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 most affected by “antimicrobial resistance”. In 2019 alone, antibiotic-resistant infections caused nearly 300,000 deaths. They alone are responsible for almost all of these people’s deaths 60,000 newborns each year.

But other hopes are yet to come. A number of promising new drugs developed in the area are showing potential against antibiotic-resistant bacteria. They also offer a game-changing solution to save storage space treatment.

Enmetazobactam, developed by Chennai-based Orchid Pharma, is the first antibiotic developed 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 blood infections by targeting the immune system of bacteria instead of the bacteria themselves.

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

To put it simply, the drug inhibits the “weapon” of the bacteria without causing easy resistance. This also applies to other antibiotics, including carbapenems, which are reliable “last line of defense” drugs.

Tests in 19 countries – the medicine has been approved by world regulators – as there are more than 1,000 patients who have shown its effectiveness. “The drug has shown incredible strength against these bacteria that have evolved over the years. It is administered intravenously [IV] to be transferred to hospitals, especially for critically ill patients, and it is not available over the counter,” Dr Maneesh Paul, the drug’s lead 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 be launched next year.

Dr Habib Khorakiwala, the founding chairman of Wockhardt, has explained Zaynich as “a new, unique disinfectant designed to fight all major bugs”. It was given on compassionate grounds to 30 critically ill patients in India who had not responded to any other antibiotics. Remarkably, they all survived. This will make India proud,” said Dr Khorakiwala.

Also in Phase 3 testing is Wockhardt’s Nafithromycin, called MIQNAF, a three-day oral treatment for community-acquired bacterial pneumonia with a 97% success rate. The current treatment for this disease has a resistance of up to 60%. Its tests will be completed next year and once approved, the company says it could be commercially launched late next year.

Bengaluru-based biopharma company Bugworks Research has partnered with the Geneva-based Global Antibiotic Research and Development Partnership, or GARDP, to develop a new class of antibiotics to treat severe drug-resistant infections. Currently in early Phase 1 trials, the drug is five to eight years from market readiness.

“Antibiotics are no longer effective, but the big money is in drugs for cancer, diabetes and other conditions, not antibiotics,” Anand Anandkumar, CEO of Bugworks, told the BBC. “There is little innovation because antibiotics are kept as a last resort. Big pharma doesn’t focus on antibiotic resistance. We are funded by various organizations, but less than 10% of the money comes from India.”

But that needs to change. The 2023 report on drug resistance surveillance by the Indian Council of Medical Research (ICMR), which analyzed nearly 100,000 bacterial cultures from 21 specialist care hospitals in India, highlighted worrying trends in antibiotic resistance.

IE.coli (Escherichia coli), commonly found in the intestines of humans and animals after consumption of contaminated food, was the most common bacterium.

This was followed by Klebsiella pneumoniae, which can cause pneumonia and also infect blood, cuts in the skin and the lining of the brain causing meningitis. Closer was the rise of a multidrug-resistant bacterium called Acinetobacter baumannii, which attacks the lungs of patients receiving medical care in critical care settings.

The survey found the effectiveness of antibiotics against E.coli has been declining significantly while Klebsiella pneumoniae has shown an alarming increase in drug resistance. Doctors have found that less than 15% of the main antibiotics are effective in treating infections caused by these bacteria. Of particular concern was the rise of resistance to carbapenems, an important last resort antibiotic.

“It’s like playing whack-a-mole with viruses. They evolve at an incredible speed, and we’re always playing catch-up. You remove one, another emerges. We need to innovate and learn from past mistakes,” Dr Manica Balasegaram, executive director of GARDP, told the BBC. .

It is not surprising that GARDP is focused on India. It is partnering with Hyderabad-based Aurigene Pharmaceutical Services to produce zoliflodacin, an oral antibiotic for gonorrhea, a sexually transmitted disease that is showing increasing resistance to antibiotics. GARDP has also partnered with Japanese company Shionogi to distribute cefiderocol – an FDA-approved development for the treatment of severe infections such as UTIs and hospital-acquired pneumonia – in 135 countries, with manufacturing facilities in India.

But this is only one part of the story. Doctors say that drug dispensing practices in India need to be changed urgently. The widespread use of broad-spectrum antibiotics – which target many types of bacteria but can kill good bacteria, cause side effects and increase bacterial resistance – promotes drug resistance by encouraging the emergence of drug-resistant strains of bacteria.

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

“I am very happy that we will have these new drugs. But what is also important is that we do methods that should not be used carelessly in the past. [what were once also] blockbuster drugs. Improper use and carelessness will jeopardize the longevity of these new drugs,” warns Dr Kamini Walia, a scientist at ICMR.

The rapid evolution of bacteria, which can evolve within an hour, emphasizes the urgency of a holistic approach. These include reducing disease through better water, sanitation and hygiene, improving access to vaccines, strengthening infection control policies in hospitals, educating doctors and preventing self-medication. “Combating antimicrobial resistance is a complex, multifaceted challenge tied to health measurement and system accountability,” said Dr. Walia.

The message is clear: without urgent action, we risk a future where even minor diseases may become incurable.