Irresponsible use of antimicrobials, including antibiotics, is accelerating the rise of ‘superbugs’. These superbugs are causing infections that were once easily treatable by antimicrobials but are now becoming increasingly difficult to treat and, in some cases, turning life-threatening. Unnecessary use of antimicrobials coupled with poor infection prevention measures and lack of new antimicrobials has resulted in a full-blown global health crisis of Antimicrobial Resistance (AMR). The Climate Crisis is also affecting patterns of infectious disease which may lead to an increase in the use of antimicrobial drugs and rise in AMR. While the problem of AMR has reached a tipping point in India, there are countless and yet, often unheard-of superheroes – in research labs, hospitals, and on the ground, among communities – working day and night to stop the rise of these deadly superbugs. In our SaS AMR Champions Series commemorating the World Antimicrobial Awareness Week (WAAW2021), we bring to you conversations with some of these ‘Superheroes Against Superbugs’ that we hope would inform, inspire, and encourage us all to act against AMR to ensure a healthy future for all.

Infection Disease (ID) specialists play a critical role in tackling global health problems such as tuberculosis and HIV, emerging infections such as Zika virus, COVID or Ebola and the growing threat posed by antibiotic resistance . Vijay Yeldandi is one such ID specialist with more than 25 years of experience in India and USA, specializing in handling infections in people with impaired immunity such as transplant recipients or patients of HIV. He is the Head of Infectious Diseases and Public Health at the non-profit organisation SHARE INDIA and a Clinical Professor of Medicine and Surgery at University of Illinois. He serves as a Faculty at the Center for Global Health, University of Illinois and the Public Health Foundation of India. Having won many awards both for his leadership and for his work in public health, Vijay provides technical help to many hospitals in India on Infection control and patient safety and serves as a technical advisor to NACO, Government of India on HIV Programs. Here, Vijay shares with us his thoughts on strategies to deal with AMR in India.

What, in your opinion, is a major driver of AMR in the context of human health?

The ability of pathogens to evade elimination of their population is dependent on a subpopulation. This subpopulation possesses genetic or epigenetic determinants of resistance that confer Antimicrobial Resistance (AMR). They replace the prevalent susceptible population with a resistant subpopulation after exposure to antimicrobials. They contain genes that carry resistance to antibiotics, called as resistomes. A key concept to understand is that AMR in human health occurs because of selective pressure due to direct human antimicrobial usage or as a by-product of other activities such as the use of pesticides/fertilizers/growth promoting antimicrobials in the agricultural/food production industry. Interestingly, resistomes spread can also occur because of consumption of “non-antimicrobial” medication. A good example is the use of antacids particularly the use of proton pump inhibitors. Inadequate disposal of healthcare associated waste including pharmaceutical manufacturing waste contributes to increasing prevalence of resistomes in the environment that eventually find their way into the food chain of humans. All these factors have been demonstrated to be the key drivers of AMR in India.

Hospital-acquired infections are also discussed as one of the major sources of AMR. In low-resource settings like India with high infectious disease burden and very high patient load, what kinds of strategies and policies do Indian hospitals need to combat AMR?

Healthcare-associated infections with multi-drug resistant pathogens is clearly a major problem particularly in India. The best way to reduce these infections is to adopt meticulous infection prevention practices as well as a robust surveillance system linked to national and global reporting systems. Currently, most Indian healthcare facilities require significant augmentation of resources in laboratory support for infectious diseases diagnosis as well as training and capacity building of health professionals in infection prevention activities. A proper foundation of capability in infectious disease diagnostics and infection prevention programs is a prerequisite to surveillance guided antimicrobial stewardship.

It is often said that the medical professionals are under pressure to over-prescribe antibiotics? What is your take on this? 

We cannot blame health professionals in India for their prescribing habits.

It is imperative to understand that antimicrobials used in time save lives!

A strategy to simply restrict the ability to prescribe/use antimicrobials needs to be balanced against the realities of access to health services in India particularly in rural areas. In public health, we need to remember that any coercive strategy for implementation of public policy is prone to systemic distortion as well as pervasive evasion.

  1. Systemic Distortion: The implementers of policies prescribed by the state have shown a predilection towards a blunt sledgehammer approach rather than an appreciative and sensitive minimalist but precise intervention approach accounting for human behavioral factors. This has resulted in complaints of “excesses” as well as allegations of corruption in allowing exemptions. This kind of approach usually leads to coercive methods and selective persecution of the weak while the rich and the powerful are allowed to evade the policy without consequences. To add to all of these is the inherent inadequacy of an overburdened and chronically under-resourced public health infrastructure trying to cope with an unprecedented challenge. 
  2. Evasion: Humans resent control. When policies are forcefully implemented,  people find a way to evade them. People have incentives to escape adverse impacts of policy. This leads to the normalisation of deviant behaviour and failure of policy. The cost of enforcement is not worthwhile under such circumstances. On the other hand, this will add to the very real risk of suboptimal healthcare under the present circumstances.

In summary, if human factors are neglected, it would be setting up policy for unintentional consequences.

A good policy therefore would require policymakers to place equal importance on the underlying human behaviour.

What did COVID-19 tell us about the healthcare system in India? How do these learning stay pertinent even for fighting AMR? 

The ideal approach to AMR, in the context of the COVID-19 pandemic, is integrating a foundation of high-quality clinical care with appropriate testing and epidemic control measures including voluntary, non-pharmacologic interventions. 

In India, the COVID-19 epidemic response has been characterized largely by state-imposed coercive non-pharmacologic interventions such as masking and distancing. These have now entered a state of diminishing returns. Because 80% of all infected persons are asymptomatic and of those testing positive, less than 4% have a fatal outcome, a more nuanced approach to address the epidemic is desirable. There is an almost unreal and naïve expectation that the lockdown extended for a long enough period of time will provide the principal solution. There is insufficient acknowledgement that the lockdown can at best flatten the epidemic curve, buying necessary time for building crucial credible health care systems by augmenting infrastructure and human resources. The scientific and technical response (largely non-state entities) to the epidemic in areas of diagnostic technology, vaccine and therapeutic options have far outpaced the cumbersome state regulatory apparatus in place. 

The pandemic has exposed the stark and tragic inadequacy of the health care infrastructure and human resource capacity to respond to this unprecedented public health emergency.

The chronic systemic neglect of public health, environmental degradation, and complete disregard for the role of animals in human health needs a transformational paradigm shift towards the goal of “One Health”. COVID-19 is a warning wakeup call from nature, we ignore it at our own peril.

Also, there has been a dramatic increase in antibiotic usage during the pandemic almost completely undermining the efforts towards rational usage of antibiotics. How do we now switch gears in addressing this issue with these lessons in mind?

Misuse and overuse of antimicrobials during the pandemic and otherwise has two sides. On one hand, the patient has been persuaded that they will not get better without antimicrobials. On the other hand the clinician is convinced that they are doing patient good by giving them antimicrobials rather than risk their health deteriorating. An ideal strategy to tackle this issue should look at the problem from both ends: the supply side and the demand side. 

On the supply side, my strategy recently has been to allow the clinician to go ahead with the prescription if he believes it will help the patient. But if they need help in rationalising the usage or if they are insecure about withdrawing antibiotics/decreasing the dosage, then to offer guidance in helping them to decide. On the demand side, it is very important to build a relationship of trust before preaching patients about usage of antimicrobials. There needs to be an investment in participatory approach and shared vision for there to be any returns in terms of behavioral change. These days, I find myself stressing on how critical the microbiome is for our good health and the importance of not injuring the microbiome by unnecessary usage of antimicrobials. I refer to the well known association of antibiotic usage in children and the issue of obesity in humans in adult life. This is such a well known phenomenon in animals and easy for people to see the association. Referring to the side effects of antibiotics like upset stomach more easy for patients to relate to than the obscure concept of resistance.

As a physician, what is your message to people on antibiotic usage? 

  • Infectious diseases have impacted human development and history.
  • Anti-infectives save lives!
  • Timing of antimicrobials is important.
  • Picking the right drug; dose and delivery affect outcomes.
  • Antimicrobial resistance threatens to negate the benefits of antimicrobials.
  • Understanding the importance of the microbiome in human health is critical.
  • Many drugs have antimicrobial activity and adversely affect the microbiome.
  • Antimicrobials can have serious detrimental effects on health because they damage the microbiome.
  • The best way to reduce AMR and morbidity of antimicrobial use is to reduce the use of antimicrobials.
  • The best way to reduce antimicrobial use is to reduce infections by measures such as vaccines, personal and social hygiene.

The YELDANDI Prescription:

Interview by Team SaS and G Bhargavi Krishna Sree; Bhargavi is a research scholar, with an inclination to study and understand the coordination between the synthesis of various cell wall components in bacteria. She uses E. coli, an established model organism to study these natural processes.

Cover Art by Mahek Kothari