Strengthening hospital epidemiology & infection prevention research capacity in India to curb antimicrobial resistance

Antimicrobial resistance (AMR) burden in India is among the highest in the world1. One of the significant contributors of AMR burden in India is healthcare-acquired infections (HAIs). Healthcare facilities are often the starting point or multiplier for AMR infections, which can contribute to further transmission in the community locally and internationally2. HAIs are highly prevalent in Indian hospitals. Although country-wide HAI rates are not available, an earlier study3 in intensive care units (ICUs) in 40 Indian hospitals found pooled device-associated HAI rates to be substantially higher than the United States Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network median rates, despite Indian ICUs having lower device utilization ratios. Central line-associated bloodstream infection (CLABSI) rates in Indian ICUs were reportedly at least five times higher than rates in the United States ICUs3. More concerning is the high prevalence of AMR among organisms causing these infections. The Indian Council of Medical research (ICMR) HAI surveillance network, involving 26 tertiary care hospitals in India, reported that carbapenem resistance in Escherichia coli, Acinetobacter species, Klebsiella species and Pseudomonas species causing CLABSIs ranged from 53 per cent (Pseudomonas species) to 77 per cent (Acinetobacter species)4. Among catheter-associated urinary tract infections (CAUTIs), the carbapenem resistance was reportedly 62 per cent in E. coli and 76 per cent in Klebsiella species4. In contrast to India, in the United States, carbapenem resistance in the same pathogens among CLABSIs is substantially lower ranging from 1.2 per cent (E. coli) to 33.1 per cent (Acinetobacter species), while among CAUTI, carbapenem resistance was 0.6 per cent in E. coli and 7.2 per cent in Klebsiella species5.

The high prevalence of AMR in HAIs warrants the need to better understand the drivers of AMR in Indian hospitals. However, there is a paucity of knowledge on factors contributing to AMR in HAIs in Indian hospitals; as a result, the optimal prevention measures needed to inform interventions to counteract AMR are mostly unknown. Interventions proven to be successful in high-income countries may not be applicable to Indian hospitals, due to differences in the epidemiology of HAIs, hospital infrastructure and care delivery models, cultural practices, along with financial and skilled personnel resource limitations. One example of this is the microbiology of HAIs in India compared to high-income countries. Klebsiella species with high prevalence of carbapenem resistance are the primary cause of hospital-onset bloodstream infections in India, whereas in the United States, Gram-positive organisms (coagulase negative Staphylococcus) are primary causes of hospital-onset bloodstream infections4,6,7. A recently published study8 from a neonatal ICU in India in collaboration with Johns Hopkins University found that the highly-resistant, Gram-negative pathogens causing neonatal sepsis are acquired from the hospital environment, rather than from maternal vaginal or intestinal flora. Another recent study performed in two Indian hospitals in collaboration with Washington University in St. Louis reported that approximately half of the hospital-onset bloodstream infections were preventable when infection prevention measures are strictly followed, and central lines were the major source of hospital-onset bloodstream infections6. These two studies indicate the importance of understanding the factors contributing to antimicrobial resistant HAIs in the Indian context. Many such high-quality studies focusing on AMR epidemiology in Indian hospitals are necessary to design appropriate intervention measures.

Improving basic infection prevention and control (IPC) measures and HAI surveillance in hospitals is the primary step. Accordingly, the Indian government undertook several initiatives during the recent years. The Kayakalp programme was initiated in 2015 to improve cleanliness, hygiene and infection control practices in public healthcare facilities9. In collaboration with All India Institute of Medical Sciences, New Delhi, and National Centers for Disease Control, ICMR, established the HAI surveillance network in 2016, with support from the United States CDC4 and also published hospital infection prevention guidelines in 201710. With advancements in basic IPC measures and HAI surveillance capacity, it is the ideal time to increase hospital epidemiology research capacity to address the issue of antimicrobial resistant HAIs. This involves creating a pool of hospital epidemiology researchers in India by developing an interdisciplinary research programme that includes clinicians, epidemiologists, microbiologists, bioinformaticians, hospital engineers, healthcare economists and social scientists. This can be addressed by creating a long-term institutional programme that trains junior clinicians locally. There are currently no formal training programmes aimed at building capacity in hospital epidemiology and infection control research in India. The presence of ICMR HAI surveillance network is an ideal opportunity to initiate and implement such a training program. The training should focus on understanding HAI epidemiology, using advanced research tools such as whole genome sequencing, metagenomics and designing intervention studies applicable to an Indian healthcare setting. Like the two international collaborative studies mentioned above6,8, there are several studies that need to be undertaken, such as focusing on colonization burden and transmission dynamics of carbapenem resistant organisms (CROs) among hospitalized patients. Results from these studies will inform subsequent or simultaneous intervention studies designed to reduce the burden of CRO. Design of these intervention studies should consider the effectiveness, feasibility, cost-effectiveness and cultural acceptability in an Indian context. The target candidates for this training programme could be either clinical microbiologists or infectious diseases physicians selected from the HAI surveillance network hospitals. Dedicated time for didactic and research activities should be considered either during senior residency or during their tenure as Assistant Professors.

At present, effective and accessible antimicrobial agents active against New Delhi metallo beta-lactamase (NDM)-producing Gram-negative organisms are lacking. The high burden of HAIs involving carbapenem-resistant Gram-negative organisms that produce NDM in India is concerning. Even if new antibiotics become available for NDM-producing Gram-negative bacteria, these will not be readily accessible due to higher cost. Considering the lack of effective therapies and the potential for further transmission of antimicrobial resistant organisms that are acquired through HAIs in the community locally in India and internationally due to global travel, it is imperative to focus efforts on preventing highly antimicrobial resistant HAIs in low- and middle-income countries. The Indian government should consider investment into interdisciplinary hospital infection prevention research training programmes in partnership with funding agencies, such as the United States National Institute of Health, the Centers for Disease Prevention and Control, the Wellcome Trust and the Bill and Melinda Gates Foundation. Advancing knowledge on contextual infection prevention measures in healthcare facilities in AMR hot spot countries such as India is critical to address the AMR pandemic.

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