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Introduction: International guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter(CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach. Methods: Patients with CRAB bacteraemia, ventilator-associated pneumonia (VAP), or both were categorized based on whether they received combination therapy or monotherapy. The 30-day mortality was compared between the two groups. Inverse probability treatment weighting (IPTW) was done using propensity score (PS) for a balanced comparison between groups. Results: Between January 2021 and May 2023, of the 161 patients with CRAB bacteraemia (n= 55, 34.2%), VAP (n= 46, 28.6%), or both (n= 60, 37.3%) who received appropriate intravenous antibiotic therapy, 70% (112/161) received monotherapy, and the rest received combination therapy. The overall 30-day mortality was 62% (99/161) and not different (p= 0.76) between the combination therapy (31/49, 63.3%) and monotherapy (68/112, 60.7%) groups. The propensity score matching using IPTW did not show a statistical difference (p= 0.47) in 30-day mortality for receiving combination therapy with an adjusted odds ratio (OR) Pof 1.29 (0.64, 2.58). Conclusion: Combination therapy for CRAB infections needs further study in a randomised controlled trial, as this observational study showed no difference in 30-day mortality between monotherapy and combination therapy.

Introduction: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae(CRKp) infections and their impact at a tertiary care hospital in South India. Methods: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014–2015; C2, 2021–2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. Results: A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p= 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p= 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-β-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. Conclusions: CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.