P40 Evaluation of sulbactam/durlobactam activity against carbapenem-resistant <i>Acinetobacter baumannii</i> in India: an institutional experience

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) is a WHO designated ‘critical priority’ pathogen because of its high capacity for multidrug resistance and association with mortality rates approaching 50% in severe hospital-acquired infections. CRAB is a major driver of ventilator-associated pneumonia (VAP), bloodstream infections and wound infections in critically ill patients, especially in intensive care units. Treatment options are severely limited, with colistin and minocycline often used as last-resort agents despite toxicity concerns. The recently concluded ATTACK trial demonstrated that sulbactam/durlobactam, a novel β-lactam/β-lactamase inhibitor combination, was superior to colistin in terms of efficacy and safety, establishing it as a preferred therapeutic option in global guidelines. Surveillance programmes have consistently reported very high activity, with more than 96% of CRAB isolates worldwide remaining susceptible. However, antimicrobial resistance (AMR) in India is distinct, with carbapenem resistance driven not only by OXA-type carbapenemases but also by endemic metallo-β-lactamases (MBLs) and frequent treatment exposures to broad-spectrum agents. Therefore, regional evaluation of sulbactam/durlobactam is crucial before incorporation into local treatment algorithms. Methods A prospective laboratory-based surveillance was conducted over four months at a tertiary-care teaching hospital. A total of 175 non-duplicate CRAB clinical isolates were collected. The majority originated from respiratory samples (n=140; 80%), reflecting the heavy burden of ventilator-associated and hospital-acquired pneumonia. Additional sources included blood (n=18; 10%), pus/wound swabs (n=7; 4%) and other sterile body fluids (n=10; 6%). All isolates were confirmed as A. baumannii by VITEK MS® (bioMérieux®, France). Antimicrobial susceptibility testing was performed by disc diffusion, and sulbactam/durlobactam activity was assessed using CLSI-M100 2024. A. baumannii SAMN04901667(AR Bank) was included as a quality control strain. Comparative susceptibility to colistin and minocycline was also assessed. Results Sulbactam/durlobactam exhibited susceptibility in 120 of 175 isolates (68.6%). Non-susceptibility was noted in 31.4% of isolates, substantially higher than resistance rates reported in global surveillance (&amp;lt;2%) or European studies (87.9–96% susceptibility). In contrast, minocycline and colistin demonstrated higher retention of activity, with susceptibility rates of 92.0% (161/175) and 94.0% (164/175), respectively. Respiratory isolates dominated the dataset, accounting for 80% of cases, consistent with India’s disproportionate burden of ventilator-associated pneumonia. No difference in sulbactam/durlobactam susceptibility was observed across specimen types. Conclusions This study provides the first institutional-level data from India on sulbactam/durlobactam activity against CRAB. Unlike international reports where the agent has emerged as a highly reliable option, our findings reveal considerably reduced susceptibility, with nearly one-third of isolates resistant. This discrepancy likely reflects region-specific resistance mechanisms, such as mutations in penicillin-binding protein 3 (PBP3), the target of sulbactam, or the presence of MBLs that confer cross-resistance. The high prevalence of combination resistance mechanisms in Indian CRAB strains may further compromise efficacy.