Linking access to stewardship: a pathway for introducing reserve antibiotics in India

Abstract

India faces a dual challenge of poor access and inappropriate use of antibiotics, fuelling antimicrobial resistance. In this context, the appropriate use of novel antibiotics demands innovation in their introduction into clinical practice in Indian healthcare settings. Novel stewardship-linked differential access pathways for health care facilities based on good antibiotic stewardship practice could offer a feasible solution. Early planning, targeted stewardship strategies and real-time monitoring are critical to developing scalable models for introduction and usage of reserve class of antibiotics in India. Such models may provide lessons learned that could be adapted and adopted by settings or countries beyond India.

Antimicrobial resistance (AMR) is a pressing global health threat. Known as a ‘silent pandemic’, it undermines the efficacy of antibiotics and complicates the treatment of infections. In 2021, AMR directly caused 1.14 million deaths and about 4.7 million associated deaths. Without intervention, by 2050 AMR is expected to affect nearly 8.2 million people, disproportionately affecting low- and middle-income countries (LMICs) due to their weak healthcare infrastructure, environmental contamination and unregulated antibiotic sales and usage.^1,2 Interestingly, between 1999 and 2014, only 12 out of 25 new antibiotics were registered in >10 LMIC countries.³ Studies have indicated several factors for this, including, limited pharma companies undertaking research and development, poor regulatory frameworks, small market size and low revenue of antibiotic sales among others.⁴

In this context, India presents a particularly complex case that highlights the paradoxical problem of antimicrobial use. Here, the issue of lack of access and excess use co-exists. On one hand, patients, particularly from rural or underserved areas, lack timely access to antibiotics, which results in morbidity and at times avoidable mortality.⁵ On the other hand, the high antibiotic use, particularly of a certain formulation of antibiotics e.g. injectables especially in private settings.⁶

Reserve antibiotics, classified by WHO as drugs to be used only for confirmed or suspected infections caused by multi-drug-resistant organisms (WHO AWaRE Classification), pose a unique challenge. They must be used carefully to preserve both immediate and long-term effectiveness.⁷ However, strict stewardship restrictions may discourage the few pharmaceutical companies still investing in antibiotic R&D and could delay their introduction in LMICs such as India.⁸

Against this backdrop, we propose a new differential stewardship-linked access pathway as a promising, actionable model that has the potential to ensure accessibility as well as appropriate use.

As part of a study titled ‘Towards an Antibiotic Roadmap for the Sustainable Entry and Management of Antibiotic X’ (TANDEM-ABX), we undertook background research that was followed by consultations with key AMR stakeholders in India to conceptualize and design a stewardship-led approach for introducing reserve antibiotics.⁹ Given India’s diverse health systems, conditional access to newly launched antibiotics, especially the reserve class, based on demonstrated good stewardship practices, could help accelerate stewardship efforts in the country. Stewardship, in this framing, becomes a strategic gateway to access these newly launched reserve category antibiotics for the seriously ill after definitive microbiological diagnosis to prevent their loss due to AMR as a result of indiscriminate use.

New reserve antibiotics are usually used in restricted settings such as intensive care units or high-dependency units of tertiary care hospitals. We therefore propose the reserve class of antibiotics as an entry point for pilot testing this stewardship-linked access pathway, which we believe will ultimately influence the use of all WHO AWaRE Classification categories of antibiotics.

Operationalizing a differential stewardship-linked access pathway in India requires careful consideration of the country’s federal health governance structure. While the central government provides overall guidance and policy direction, health service delivery is largely the responsibility of individual states. This diversity means that each state may require a tailored model depending on its governance capacity, infrastructure and level of antimicrobial stewardship (AMS) maturity. Articles have underscored need for a national-level regulatory and access framework to ensure responsible introduction and use of antimicrobials in India. A recent article¹⁰ proposed such a framework and recommended restricting the use of new ‘Watch’ and ‘Reserve’ antibiotics to hospitals certified for AMS and infection prevention and control. Building on this and taking into account India’s diverse health systems, our proposed pathway translates the framework into a locally adaptable stewardship-linked access mechanism especially for the reserve class of antibiotics. This approach can help augment the national strategy with the ground-level implementation across diverse states.

The following three steps will be critical in operationalizing such a pathway. First, specific stewardship-linked procurement policies that take into consideration respective state’s infection prevention and control capacity must be developed to ensure uninterrupted availability of the antibiotic and related diagnostics to those who truly need it, while also minimizing the risk of inappropriate prescriptions. Second, AMS interventions should be embedded in broader health-system-strengthening initiatives by developing contextualized standard operating procedures, clear incentives and accountability structures in healthcare facilities. Digital tools such as web-based training modules and self-paced certification, hosted on state-run or certified platforms, can be leveraged to build AMS capacity and knowledge. Third, routine quality processes such as real-time monitoring of prescription patterns, resistance trends and clinical audits that triangulate clinical-pharmacy-laboratory data, must become regular practice. This can be done by integrating antibiotic prescription data within health system monitoring dashboards, allowing AMS committees to track usage patterns, flag inappropriate prescriptions and intervene when necessary.

For the pilot phase, states with higher-performing health systems can be prioritized. Hospitals and facilities that demonstrate good performance on core stewardship capabilities such as monitoring antibiotic use, accurate diagnostic capabilities, organizational leadership and clinician education prioritizing AMS, combined with robust infection control practices, could be identified for the introduction of newly launched reserve-class antibiotics. Importantly, such a differential access pathway for reserve antibiotics also has the potential to reduce out-of-pocket expenditure through shorter hospital stays, lower drug expenditure, preservation of drug efficacy for more patients and fewer treatment failures among patients with multi-drug-resistant infections. Furthermore, implementing such a pathway can generate real-world evidence on what works in resource-constrained settings, identify systems-level enablers and bottlenecks, and refine interventions. It will also build the evidence base necessary for scale-up across public and private sectors in other LMICs. An added advantage of tying stewardship to the introduction of reserve-class antibiotics is the positive spill-over effect. These systems, once in place, are likely to improve practices around existing Access and Watch antibiotics as well.

Our proposal (Figure 1) rests on pillars such as early planning, before the antibiotic enters the market and implementation research pilot projects to inform sustainable scale-up. The pilot will provide evidence on the feasibility of this pathway, particularly the tools for digital tracking that keep policymakers, hospital teams and AMS experts informed, support the design of training materials and enable procurement policies linked to stewardship, all crucial steps to combat antimicrobial resistance while ensuring access to life-saving antibiotics. In addition, sustained engagement with state and central policymakers will be essential to facilitate state-level adaptations and eventual national-level integration of such a pathway.

Figure 1.

TANDEM-ABX framework.

In conclusion, we strongly believe that an implementation research pilot that embeds stewardship as an integral component of the antibiotic pathway, from procurement to monitoring, can provide India with a robust local evidence base. It can also inform a sustainable access and use model for reserve antibiotics that aligns with global best practices while being tailored to the country’s diverse health system needs. As a next step, such an implementation pilot is critical as it will generate richer evidence by including more than one state in the implementation pilot, as states differ in governance (management capacity, laboratory diagnostic capabilities, infrastructure and resource capacity, as well as expenditure on health).

Funding

This study was supported by International Centre for Antimicrobial Resistance Solutions, Denmark (Project ID 100039) with a planning grant from the Novo Nordisk Foundation.

Transparency declaration

Dr Sarang Deo reports grant from International Centre for Antimicrobial Resistance Solutions for the conduct of the study. Dr Jyoti Joshi and Dr Fabian Maza-Arnedo report personal fees from International Centre for Antimicrobial Resistance Solutions during the conduct of the study. Ms. Samriddhi S. Gupte and Dr Prasannakumar Palanikumar have nothing to declare.