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The landscape of antibacterial therapies in India is evolving to address the antimicrobial resistance (AMR). Many research centres are exploring alternative antibacterial therapies. By adopting innovative approaches, India can make significant strides in addressing AMR and improving patient outcomes in the face of serious bacterial diseases, opine experts
Development of new antibacterial drugs is crucial to combat multi-drug-resistant bacterial infections. Streamlined development programs and clinical trial designs can facilitate the approval of novel antibacterial therapies, providing patients with unmet medical needs access to effective treatments. Effective treatments are essential to reduce morbidity and mortality, said Dr Nasiruddin G, consultant, internal medicine, Fortis Hospital.
According to Dr Sathvik Jain, physician, SDM Multispeciality Hospital, Ujire, “Various unmet medical needs like XDR-TB, neonatal sepsis and postoperative hospital acquired infections are serious public health concerns. Lack of novel antibacterial therapies, constant overuse of antibiotics has led to AMR”.
India faces critical gaps in antibacterial therapies. Inclusion of a more targeted approach is required. High risk patients under ICU observation, immune compromised cases etc requires integration of various therapies like monoclonal antibodies, Phage therapy etc. Also in India, proper use of better diagnostic methods, conducting research and development is required to overcome the issue, Dr Jain added.
Dr Harish Mallapura Maheshwarappa, director, Institute of Critical Care Medicine, Kauvery Hospitals, noted, that in India rising multidrug-resistant organisms, especially carbapenem-resistant Enterobacteriaceae, has created a critical unmet need for novel antibacterial therapies. Existing antibiotics are increasingly ineffective. Access to newer agents like cefiderocol or cefepime-zidebactam remains limited due to cost and regulatory hurdles. There is need for rapid diagnostics, antimicrobial stewardship, and incentivized R&D to address this crisis. Public-private collaborations and fast-track approvals could accelerate availability. Without immediate action, we risk entering a post-antibiotic era where even minor infections become life-threatening.
Dr. Sunil S Bohra, senior consultant, internal medicine, Apollo Hospital, said, “India is labelled as the ‘AMR capital’ due to surging antimicrobial resistance and limited effective treatments. In 2019, only 7.8 per cent of Indian patients with life-threatening carbapenem-resistant infections were appropriately treated, with nearly one million people succumbing annually from drug-resistant infections. New drugs and novel compounds, are under development.
Dr Swati Rajagopal, consultant, infectious disease & travel medicine, Aster CMI Hospital, stated “Many patients, especially in rural and under-resourced areas, struggle to access effective treatments for drug-resistant tuberculosis, hospital-acquired infections, and sepsis. While some progress has been made through national programmes and public-private collaborations, the pace of innovation in antibacterial drug development remains slow. Indian pharma is showing interest in developing novel antibiotics, but affordability and regulatory hurdles remain key challenges.
Improving AMS crucial for combating AMR
AMR poses a significant threat to global health, jeopardizing the effectiveness of antibiotics and other life-saving medications. Infections that were once easily treatable are becoming increasingly difficult to manage, leading to prolonged illness, disability, and even death informed Dr. Surendran R, consultant – infectious disease and hospital infection control, The SRM Institutes of Medical Science (SIMS), Chennai.
According to Dr. Surendran improving antimicrobial stewardship (AMS) is crucial in combating AMR, and the development of novel anti-infectives plays a vital role in this effort. In India, surveillance reports indicate a steady rise in resistance to both first-line and second-line antibiotics over the past six years, a dangerous trend that threatens to overwhelm our healthcare system.
AMS programmes aim to optimize antibiotic use to improve patient outcomes, minimize the emergence of resistance, and reduce healthcare costs. These programs involve a multidisciplinary approach, encompassing infection prevention, diagnostic testing, appropriate antibiotic selection and dosage, and duration of therapy. While these strategies are essential, the continuous development of novel anti-infectives remains a cornerstone in the fight against AMR.
The pipeline for new antibiotics has historically been limited, with many pharmaceutical companies shifting their focus away from anti-infective research due to economic challenges and regulatory hurdles. However, the growing recognition of the AMR crisis has spurred renewed interest and investment in this critical area.
Dr. Surendran informed that initiatives like the Indian Priority Pathogen List (IPPL), developed by the Department of Biotechnology in collaboration with the WHO Country Office for India, are helping with prioritization of research and development of new and effective antibiotics from an Indian perspective. Several promising novel anti-infectives are currently under development, offering hope in the battle against resistant pathogens.
These novel agents employ various mechanisms of action, targeting bacterial pathways that are distinct from existing antibiotics. This allows them to overcome resistance mechanisms that have rendered many current therapies ineffective.
Dr. Surendran further explained that some of these innovative approaches include targeting novel bacterial enzymes. Researchers are exploring new enzymes essential for bacterial survival, offering potential targets for drug development. Inhibiting these enzymes can disrupt critical bacterial processes, leading to bacterial death. Scientists are actively working on entirely new classes of antibiotics with unique mechanisms of action. These novel classes offer the potential to combat multi-drug-resistant organisms that are unresponsive to current therapies.
Other important area is exploring combination therapies. Combining existing antibiotics with novel agents can enhance efficacy and potentially overcome resistance mechanisms. This approach can also broaden the spectrum of activity, allowing for the treatment of a wider range of infections.
Dr. Surendran also highlighted the role of monoclonal antibodies and bacteriophage therapy. Monoclonal antibodies can be designed to target specific bacterial antigens, offering a highly targeted approach to treating infections. This approach can minimize off-target effects and reduce the risk of developing resistance.
Bacteriophages are viruses that infect and kill bacteria. This approach, while not strictly a “novel antibiotic,” offers a promising alternative to traditional antibiotics, particularly for treating multi-drug-resistant infections.
“The development and implementation of novel anti-infectives are not without challenges. Rigorous clinical trials are essential to ensure both efficacy and safety. Furthermore, strategies to prevent the emergence of resistance to these new agents must be implemented from the outset. This includes responsible antibiotic prescribing practices, robust infection control measures, and ongoing surveillance for resistance development. Beyond the development of new drugs, innovative diagnostic tools are also crucial for improving AMS. Rapid diagnostic tests can quickly identify the causative pathogen and its susceptibility profile, allowing for more targeted and effective antibiotic therapy. This reduces the unnecessary use of broad-spectrum antibiotics, minimizing the selective pressure for resistance development,” Dr. Surendran concludes.
DCC for changes in rules for regulatory oversight
Earlier the Drugs Consultative Committee (DCC), the advisory committee that advises the Central and state governments on matters that require uniform implementation of laws across the country, has recommended amendment of the rules so that the Central Drugs Standard Control Organisation (CDSCO) can have a regulatory oversight on approval of antimicrobials across the country.
The Committee, in its meeting, was considering a proposal regarding inclusion of all antimicrobials in the definition of New Drug under the New Drugs and Clinical Trial Rules (NDCTR), 2019.
After detailed deliberation, the DCC recommended that, “suitable provisions may be made in the rules for regulatory oversight by CDSCO for approving antimicrobials in the country to ensure uniformity of implementation and compliance with the rules.”
The decision follows a recommendation from the Drugs Technical Advisory Board (DTAB) in its meeting in August, 2024, where it has recommended the DCC to consider the proposal for inclusion of all antibiotics in the definition of new drugs in the NDCTR, 2019, to address the issue of AMR.
The National Programme on AMR Containment, under the National Centre for Disease Control, in a report in July, 2023, said that in 2019, 4.95 million deaths were estimated to be associated with bacterial AMR of which 1.27 million deaths were directly attributable to bacterial AMR.
“It is estimated that AMR will cause 10 million every year by 2050, becoming the number one cause of deaths globally. A major contributing factor to antibiotic resistance is overuse of antibiotics by humans, with approximately half or more of hospitals using antibiotics inappropriately,” it added. Amoxicillin and clavulanic acid 625 mg, azithromycin 500 mg, cefixime 200 mg and ceftriaxone 1g, all in the watch group, were the most commonly used antibiotics over the years.
The meeting observed that the AMR has been recognised as a serious and growing threat to public health globally. It has also been highlighted as a global health priority in multiple high-level florae ranging from the UNGA, G7 to G20. In this context, it was proposed to include all antibiotics in the definition of new drug in the NDCG Rules, 2019.
The Board deliberated the matter and observed that the G20 declaration stated for tackling the issue of antimicrobial resistance.
“Antimicrobial resistance can be caused by due to misuse of antibiotic, antiviral, antifungal, etc. and accordingly recommended that the matter may be deliberated in the DCC initially,” according to the minutes of the meeting.
AMR emerges as major global health crisis
According to an earlier study, AMR is emerging as one of the major health crises being faced by the entire world. And this is not the health crisis of the present generation alone, as it is going to be the biggest health crisis of the next generation too, if not tackled in time.
The global community has declared AMR as a public health crisis and the regulators world over, including the Indian regulators, have already initiated measures to tackle the issue on war footing as they are seized of the grim scenario.
AMR is a gathering storm that threatens a century of progress in medicine. Each year, drug-resistant bacteria claim more than a million lives globally, especially in low- and middle-income countries. Yet this crisis is still a silent one. It is often observed that the availability of life-saving medicines over-the-counter makes matters worse as people tend to purchase antibiotic drugs even for illnesses which are due to a virus rather than a bacterium.
Experts have already red flagged over the looming grim situation, if necessary, steps are not taken immediately. Even though AMR also occurs naturally over time, indiscriminate use of antibiotics is one of the major reasons for the emergence of AMR. The hard fact is, misuse and overuse of antibiotics are threatening to undo decades of medical progress.
The gravity of the situation can be gauged from the words of none other than the WHO Director General Dr Tedros Adhanom Ghebreyesus who stated that AMR threatens to unwind centuries of progress in human health, animal health, and other sectors and it is a growing and urgent crisis which is already a leading cause of untimely deaths globally. More than two people die of AMR every single minute in the world.
A strategic roundtable on ‘Charting a new path forward for global action against AMR’, organised at the 77th World Health Assembly, the apex decision-making body of the World Health Organization (WHO) had stressed on the need to accelerate action against AMR.
When antibiotics are so readily available, there is no imperative for them to be treated with the care they needed. Yet another fact is that the burden of AMR falls disproportionately on low- and middle-income countries, where healthcare systems are overburdened, and resources are stretched.
It is true that AMR has been hitting the headlines for the last some years as it has become a serious and growing public health issue that threatens the effective prevention and treatment of an increasing range of bacterial infections.
Interestingly, the emergence of resistance is not only limited to the older and more frequently used classes of drugs but there has also been a rapid increase in resistance to the newer and more expensive drugs.
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