Stewardship as the way forward in fighting global antimicrobial resistance

With the World Health Organization's emphasis on stewardship and working together against antimicrobial resistance (AMR), the authors consider the importance of certain agents in preventing AMR. Looking at the 2010 superbug crisis in India, they find that the withdrawal of multinational firms from the carbapenem market caused Indian firms to fill the void and physicians to switch their product preferences. They highlight the importance of scientific publications in reporting and monitor outbreaks, and the need to incentivise antibiotic innovation.

This week, until 24 November, the World Health Organization (WHO) is organising World Antimicrobial Awareness Week (WAAW). It seems to be keeping the idea of stewardship at the forefront of its activities – appositely, the theme this year is ‘Preventing Antimicrobial Resistance Together’. One should laud WHO for this, given the critical nature of the grand global challenge of antimicrobial resistance (AMR). Some earlier estimates pointed out that AMR costs were as high as $1 trillion in 2019 (Dadgostar 2019), with deaths from AMR in 2019 estimated at around 1.27 million (Antimicrobial Resistance Collaborators 2022). One can safely expect this number to have gone up in 2022, especially with the Covid-19 pandemic still swirling around.

Agents critical to curbing AMR

In a recent study (Aggarwal et al. 2023), we found that some agents are more critical in preventing AMR than others. In our research, we exploit the 2010 Lancet coverage of the NDM-1¹ super bug crises in India (Kumarasamy et al. 2010), which reported the existence of a carbapenem resistant superbug discovered in Delhi which subsequently spread to over 70 countries around the world. As carbapenems are the most advanced form of antibiotics today, it would have been indeed worrying if a bug was found resistant to it. We show that this was indeed the case – in fact, there were additional reasons for concern.

The upstream research shock from the Lancet publication causally impacted unconnected downstream product markets in antibiotics in India. The discovery and reporting of the superbug caused multinational firms selling carbapenems in India to reduce their downstream market exposure, selling less, and withdrawing from the local Indian carbapenem market over time. Rational antibiotic stewardship would have implied that one should expect a similar response from domestic Indian firms, and indeed from local clinicians. Unfortunately, we observed the opposite in our data, with local clinicians and firms failing to perform their stewardship role. Domestic Indian firms filled the void in the market left by multinational firms: Indian physicians prescribed fewer multinational products and switched their preferences towards domestic firms’ products. Our results were robust to a variety of tests and other sensitivity analyses. Clearly, the findings have serious implications for not just AMR, but also for global health and innovation policy, especially given WHO’s focus on WAAW 2022.

First, our findings point to the criticality of robust science in reporting superbugs and pathogenic outbreaks, as we witnessed with the Lancet publication. The Berlin Outbreak database is one such global effort aimed at using peer-reviewed science to monitor infectious disease outbreaks worldwide. Although one cannot overstate the welfare effects of such science-based monitoring of pathogenic outbreaks, much more needs to happen by leveraging creative approaches like wastewater monitoring, and other techniques that the world has learnt from the Covid-19 crisis.

Second, the fact that domestic companies and local Indian physicians switched their preferences is also perturbing. We certainly must prevent AMR together, but some agents in the ecosystem play a more crucial role here than others.

Role of innovation

While subsequent regulations in India have made it more difficult for antibiotics to be available over the counter without prescriptions, but diagnosing microbial resistance through genomic testing in culture labs is still not affordable. Innovations like easy-to-use diagnostic tests will increasingly play an important role, specifically to cope with the empirical evidence we found on lack of stewardship in our data. This problem is not just seen in the India context, as the indiscriminate prescription of antibiotics is on the rise in other populous countries such as Brazil as well (Volpato et al. 2005).

Finally, what does this mean for the availability of new antibiotics? Unfortunately, the answer is not encouraging. The need of the hour is a mission mode response to the global harmonisation of efforts in restoring incentives for antibiotics innovation. The US Generating Antibiotic Incentives Now (GAIN) Act of 2012 was a start, but ever since the 2010 discovery of the NDM-1 superbug, many have bemoaned that much more is needed. An all-hands-on-deck approach, not just from global social planners but also from entrepreneurs, established firms, clinicians and healthcare providers, among others, as well as communicating with patients is necessary. If not, when the next zoonotic disease outbreaks occur – especially if they are bacterial ones – it may be too late, and the antibiotic panaceas available in humanity’s quiver will be slim.

Note:

NDM-1 stands for New Delhi metallo-beta-lactamase-1, which refers to a gene’s protein product that some bacteria produce. A bacterial strain that carries NDM-1 is resistant to antibiotics.