As we continue to tackle the challenges of antimicrobial resistance, time to factor in newer, emergent issues

The World Health Organization (WHO) has declared AMR as one of the top 10 global health threats.

A new antibiotic after 30 years

In its effort to tackle AMR, Mumbai-based pharmaceutical company Wockhardt, with support from the Biotechnology Industry Research Assistance Council (BIRAC) has launched Nafithromycin marketed as ‘Miqnaf’ to treat Community-Acquired Bacterial Pneumonia (CABP). It is a once-a-day, three-day treatment for CABP with a 97% success rate. It is India’s first indigenously-developed antibiotic in its class. It was also the first antibiotic to be developed in the last 30 years, globally.

“Nafithromycin is a part of our overall drug discovery programme which we started about 25 years ago,” said Habil Khorakiwala, founder-chairman, Wockhardt. “[While] Azithromycin and other drugs were there, there was no new drug coming [up] and resistance was developing on [the other] end”, he added. The drug was developed over a span of 15 years. 

With slow progress in research in the field of antibiotics, no new drugs have been developed in the past three decades globally. “After the initial boom and the “golden age” of antibiotics (from 1940 to 1960), the field was marked by a sharp decline in new antibiotic approvals for decades,” said Tomislav Mestrovic, affiliate associate professor of Health Metrics Sciences, at IHME, responding to questions via mail. 

It is no wonder then that with the development of Nafithromycin, India has reached a milestone given it has the highest burden of bacterial infections.

Gaps in healthcare system

While scientific advancements like Nafithromycin are promising, it is also important for us to recognize the gaps within India’s healthcare system that prevent effective treatment against AMR. 

Vysakh, Mr. Viswanathan’s son, a PhD scholar in Poland, said a communication gap exists between medical professionals and the patient’s family members. A lapse he believes the medical community also needs to address is the quality of equipment being used. “Another pitfall that happens is diagnostic issues,” he pointed out. “It took at least one week to get a proper antibiogram delivered and to figure out [which] bacteria is causing infection and to [administer] the specific antibiotic. So this was a big problem”. He also added that there was an issue of accountability within the system. 

Vysakh’s family’s plight is unfortunately a common scenario across the healthcare system. “Understaffing of healthcare professionals combined with high patient loads makes it difficult to ensure adherence to best stewardship practices,” said Dr. Mestrovic while speaking about the key challenges India faces in implementing effective antimicrobial stewardship across its healthcare network. 

Apart from these issues, India also faces the added challenge of self-medication by people, selling of antibiotics without prescriptions and lack of a proper regulatory framework. “[In] a lot of low-to-middle income countries you can go to a pharmacy and they will give you an antibiotic without any prescription,” said François Franceschi, head of asset evaluation and development and serious bacterial infections project leader, Global Antibiotic Research & Development Partnership (GARDP), as he recalled his experience at a pharmacy in Mumbai. 

Despite antibiotics being prescription drugs in India they are sold over-the-counter, contributing significantly to the resistance problem. “Part of the action plans that [are] trying to be implemented in many countries is [to] stop letting people buy antibiotics without prescription. That’s a big step and that should happen because otherwise, you know, you are fighting a battle that you’re going to lose”, said Dr. Franceschi. 

What the government is doing

The Indian government is working on multiple fronts to combat AMR including establishing AMR surveillance networks, developing a National Action Plan and promoting public awareness. “The implementation of the National Action Plan on AMR in 2017 marked a key milestone in aligning the country’s efforts with the global strategy, and this is the right path forward,” said Dr. Mestrovic. 

Promoting public awareness is a key aspect that needs to be addressed from the very beginning. It is not uncommon to see people take antibiotics for a viral fever which is not only ineffective but adds to resistance. “Public awareness about AMR remains low, leading to patient demand for antibiotics even when not needed which is not characteristic only for India, but much wider,” said Dr. Mestrovic. 

The pressing need to educate people about the dangers of inappropriately using antibiotics resonates with all the experts in the field.

Resistance is a natural phenomenon in microorganisms. But it happens over time, through genetic changes and adaptations. However, the widespread and excessive use of antibiotics across sectors has accelerated the process. It is quite natural to wonder then what the future of the new antibiotics that are being developed looks like. “Long-term effectiveness of new antibiotics depends not only on scientific advancement, but also on responsible global stewardship from day one,” said Dr. Mestrovic. “Patient education and public awareness are indispensable in the fight against AMR, especially when we are talking about the misuse and overuse of antibiotics.”

Education, innovation and regulation need to progress parallelly to curb AMR. “I think it’s very important that governments recognise that we need to do something now or we are going to be facing a problem that is much bigger in the future,” said Dr. Franceschi. “We need to be multiple steps ahead of [pathogens]”.

The long path ahead

Nafithromycin is a start and will be launched in the market for a month in the coming few months. The development of antibiotics is a long and resource-intensive process. With a lack of fundamental research in the field, the development of antibiotics also takes a backseat. “Many large pharmaceutical companies exited the antibiotic space because the return on investment was too low compared to chronic disease drugs leading to what many called the “antibiotic innovation gap”, said Dr. Mestrovic. 

Institutions like Bangalore Bioinnovation Centre (BBC) and the Centre for Cellular and Molecular Platforms (C-CAMP) and companies like Wockhardt, Orchid Pharma and Bugworks in India are among the few companies that focus on antibiotic development. 

Given the low return on investment, it is mostly small pharma companies taking on the challenge of developing new antibiotics during this crisis. And the path is not easy, especially when it comes to clinical trial approval by the Central Drugs Standard Control Organization (CDSCO). “We expect the regulators and the government as a whole to have a much better appreciation of fundamental drug research and make more enabling policies for us,” said Dr. Khorakiwala. 

Accessibility and affordability are other important factors in the development of new antibiotics. Wockhardt’s strategy is to price its drugs based on the purchasing power of different countries. For example, the price of a drug in India could be up to 80% less than the price in the United States. “Accessibility is as important as finding a new drug”, added Dr. Khorakiwala. 

For Vysakh, the issue is deeply personal. His story is a reminder of the harsh reality of AMR – a silent threat unnoticed by many.  And his experience sheds light on the challenges families face in healthcare facilities in India. “I would really love to see two major changes – diagnostics and proper quality control for the equipment used,” he said. He also believes education has to be the first step in this fight against AMR along with stringent regulations around the distribution of antibiotics. 

Emerging resistance to newer formulations

Infectious diseases experts have also flagged emerging resistance to newer drug formulations too, more recently. Abdul Ghafur, founder, AMR Declaration Trust, in a letter to the Drugs Controller General of India cautioned that misuse of newer molecules is leading to initial signs of resistance as reported by The Hindu. Ceftazidime-avibactam. a new and potent antibiotic, he claimed, is losing efficacy due to extensive, irrational, and uncontrolled use. The drug, which was initially registered with the U.S. FDA in 2015 and approved in India three years later, is a last-line antibiotic. It is to be used as targeted therapy for certain carbapenem-resistant gram-negative infections and not prescribed as a broad spectrum antibiotic. Experts say that it is more than ever before, important for the government to lead antibiotic stewardship, at this stage, as newer molecules are finally enter the market.

Addressing AMR is no longer optional and tackling it requires a multifaceted approach with a shared sense of responsibility to make a difference. “Combating AMR is not just a scientific or medical challenge, it is a collective responsibility that requires coordinated action across sectors, as well as sustained investment and empowered communities,” said Dr. Mestrovic. “We have the right tools, knowledge and innovation to make a difference, but success depends on translating awareness into action at every level – from policymakers and researchers to the medical community and the public.”

(Soujanya Padikkal is a freelance content provider based in Hyderabad. Email: [email protected])