India Advances Drug Development to Combat Deadly Superbugs

While antibiotics have been celebrated as medical saviors, they are increasingly confronted by a formidable challenge: bacteria that evolve, adapt, and overcome the medications intended to eliminate them and treat the resulting infections. These “superbugs,” resistant to antibiotics, were directly responsible for 1.14 million fatalities globally in 2021, as reported by the medical journal The Lancet. In the majority of these instances, antibiotics—regarded as the primary defense against severe infections—proved ineffective. India is counted among the nations most significantly impacted by “antimicrobial resistance.” In 2019 alone, infections resistant to antibiotics led to approximately 300,000 deaths within the country. Furthermore, these infections are solely accountable for the deaths of nearly 60,000 newborns annually. Nevertheless, a glimmer of hope is emerging. Several promising new drugs, developed domestically, demonstrate the capacity to combat antibiotic-resistant pathogens. These innovations also present a crucial opportunity to safeguard the efficacy of last-resort treatments. Enmetazobactam, a product of Chennai-based Orchid Pharma, marks the first antimicrobial developed in India to receive approval from the US Food and Drug Administration (FDA). This injectable medication addresses serious ailments such as urinary tract infections (UTIs), pneumonia, and bloodstream infections by focusing on the defense mechanisms of bacteria, rather than the bacteria directly. Bacteria frequently generate enzymes, such as beta-lactamase, which are designed to dismantle antibiotics. Enmetazobactam forms a strong bond with these enzymes, thereby neutralizing them and enabling the antibiotic to effectively eliminate the bacteria. Essentially, the drug disarms the bacteria’s “weapon” without readily inducing resistance. This action also helps maintain the efficacy of other antibiotics, including carbapenems, which are considered dependable “last line of defence” medications. Its efficacy has been demonstrated in trials conducted across 19 countries, involving over 1,000 patients, and the drug has received approval from global regulatory bodies. Dr. Maneesh Paul, the lead co-inventor of the drug, informed the BBC that “The drug has shown remarkable potency against these bacteria that have evolved over the years. It is administered via intravenous [IV] infusion in hospitals, specifically for critically ill patients, and is not available over the counter.” Wockhardt, a company based in Mumbai, is currently evaluating a novel antibiotic named Zaynich, intended for severe drug-resistant infections. This medication, which took over 25 years to develop, is presently undergoing Phase-3 trials and is anticipated to be introduced to the market next year. Dr. Habib Khorakiwala, the founder chairman of Wockhardt, characterized Zaynich as a “ground-breaking, one-of-its-kind new antibiotic designed to combat all major superbugs.” It was given to 30 critically ill patients in India, who had not responded to any other antibiotics, under compassionate use provisions. Notably, every patient survived. Dr. Khorakiwala stated, “This would make India proud.” Additionally, Wockhardt’s Nafithromycin, marketed under the trademark MIQNAF, is undergoing Phase-3 testing. This is a three-day oral treatment for community-acquired bacterial pneumonia, demonstrating a 97% success rate. Current treatments for this condition face resistance levels as high as 60%. The trials for MIQNAF are scheduled to conclude next year, and if approved, the company indicates it could be commercially launched by late next year. Bugworks Research, a biopharma company based in Bengaluru with 30 employees, has formed a collaboration with the Geneva-based non-profit Global Antibiotic Research and Development Partnership (GARDP). Their objective is to develop a novel class of antibiotics for addressing severe drug-resistant infections. This drug is presently in early Phase-1 trials and is estimated to be five to eight years away from being ready for market. Anand Anandkumar, CEO of Bugworks, conveyed to the BBC that “Antibiotics are becoming less effective, but big money is in drugs for cancer, diabetes and other conditions, not antibiotics.” He added, “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.” However, this situation requires alteration. A 2023 drug resistance surveillance report from the Indian Council of Medical Research (ICMR), which examined nearly 100,000 bacterial cultures sourced from 21 specialized care hospitals across India, underscored concerning patterns in antibiotic resistance. E.coli (Escherichia coli), typically present in the intestines of humans and animals following the ingestion of contaminated food, emerged as the pathogen most frequently identified. Next in prevalence was Klebsiella pneumoniae, capable of causing pneumonia and infecting the blood, skin incisions, and the brain’s lining, leading to meningitis. Closely following was the emergence of the multidrug-resistant pathogen Acinetobacter baumannii, which targets the lungs of patients receiving life support in critical care settings. The survey revealed a consistent sharp decrease in antibiotic effectiveness against E.coli, while Klebsiella pneumoniae exhibited an alarming increase in drug resistance. Physicians observed that some primary antibiotics were less than 15% effective in treating infections caused by these pathogens. The most significant concern was the growing resistance to carbapenems, an essential last-resort antibiotic. Dr. Manica Balasegaram, executive director of GARDP, conveyed to the BBC, “It’s like playing whack-a-mole with bacteria. They evolve at an incredibly fast pace, and we’re always playing catch-up. You get rid of one, another pops up. We need more innovation and to learn from past mistakes.” Unsurprisingly, GARDP is directing its attention towards India. The organization is collaborating with Hyderabad-based Aurigene Pharmaceutical Services to manufacture zoliflodacin, a new oral antibiotic designed for gonorrhea, a sexually transmitted disease that is exhibiting growing resistance to existing antibiotics. Furthermore, GARDP has partnered with the Japanese pharmaceutical company Shionogi to facilitate the distribution of cefiderocol—a groundbreaking, FDA-approved antibiotic for challenging infections such as UTIs and hospital-acquired pneumonia—across 135 countries, with intentions for its production in India. However, this represents only one facet of the issue. Medical professionals assert that drug prescription practices in India are in urgent need of reform. The extensive use of broad-spectrum antibiotics—which target numerous types of bacteria but can also eliminate beneficial bacteria, lead to side-effects, and escalate antibiotic resistance—contributes to drug resistance by fostering the development of drug-resistant bacterial mutants. Instead, doctors recommend prioritizing narrow-spectrum antibiotics. Yet, hospitals frequently lack antibiograms—microbiology-based guidelines for antibiotic use—which compels physicians to prescribe “broadly and blindly.” Dr. Kamini Walia, a scientist at ICMR, cautioned, “I am definitely excited that we will have these new drugs. But what is also important is that we should create mechanisms that they should not be misused the way we have previously done with [what were once also] blockbuster drugs. Improper and irresponsible use will compromise the longevity of these new drugs.” The swift mutation of bacteria, capable of evolving within hours, emphasizes the critical need for a comprehensive strategy. This encompasses measures such as reducing infections through enhanced water, sanitation, and hygiene practices, increasing vaccine adoption, reinforcing hospital infection control protocols, educating medical practitioners, and discouraging self-medication among patients. Dr. Walia stated, “Combating antimicrobial resistance is a complex, multi-faceted challenge tied to healthcare equity and systemic accountability.” The implication is unambiguous: without prompt intervention, there is a risk of a future where even comparatively minor infections could become impossible to treat.