Mortality and cost of therapy of carbapenem susceptible vs resistant Gram-negative infections among hospitalised patients in India: a multicentric surveillance (2022-2025).

BACKGROUND

India bears one of the highest burdens of Gram-negative bacterial infections, yet their burden and associated mortality remain poorly characterised. We aimed to determine and compare the mortality and cost of therapy for susceptible and resistant Gram-negative bacterial infections from a multicentric hospital-based surveillance in India.

METHODS

This multicentre observational study analysed ICMR antimicrobial resistance surveillance network data from April 2022 to April 2025 across 20 tertiary care hospitals in India. We enrolled hospitalised patients with microbiologically confirmed gram negative infections caused by Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Mortality among patients with carbapenem resistant infections was compared with phenotypically susceptible infections of the same species. Secondary outcomes included length of stay, cost of therapy and treatment patterns with ceftazidime-avibactam or polymyxin based therapy.

FINDINGS: Among 159,336 hospitalised patients (1,759,597 patient-days), 27,283 (17.1%) were microbiologically confirmed and 26,213 (16.4%) patients had Gram-negative bacterial infections. The mean age of the study population was 51.2 years (SD 18.3), and 67.8% of them were males and 32.2% were females. Patients with carbapenem-resistant (CR) infections were associated with a higher risk of mortality than susceptible infections across all major pathogens studied: E. coli [relative risk (RR) 1.41, 95% CI 1.13-1.70; population attributable fraction (PAF) for mortality 15.8%], K. pneumoniae [RR 1.33, 95% CI 1.18-1.51; PAF 17.5%], A. baumannii [RR 1.16, 95% CI 1.02-1.34; PAF 11.1%], and P. aeruginosa [RR 1.43, 95% CI 1.15-1.92; PAF 18.7%]. Bloodstream infections due to carbapenem resistant non-fermenters had the highest mortality (46.4-50.8%). CR E. coli and K. pneumoniae were predominantly treated with ceftazidime-avibactam over polymyxin B. Antibiotic treatment costs were 1.1-2 folds higher for resistant infections.

INTERPRETATION: Out findings suggest that CR Gram-negative infections are associated with high mortality and cost of therapy in tertiary care hospitals in India. These findings underscore the urgent need to strengthen surveillance, infection prevention and control and to improve access to effective therapies through strong antimicrobial stewardship initiatives.

FUNDING: Task force project of the Indian Council of Medical Research.