Ceftazidime-Avibactam Versus Colistin-Based Regimens for Carbapenem-Resistant Enterobacterales Bloodstream Infections: A Six-Year Retrospective Cohort and 30-Day Mortality Analysis.

Abstract

Bloodstream infections (BSIs) caused by carbapenemase-producing Enterobacterales (CPE) carry a high mortality, and comparative real-world data remain limited, particularly for metallo-β-lactamase (MBL) and dual-carbapenemase producers. We conducted a single-centre, six-year (2020-2025) retrospective study of 308 adults with CPE BSIs at a Romanian tertiary hospital, applying multivariable logistic regression, Cox proportional-hazards models with a 72 h landmark analysis, and inverse-probability-of-treatment-weighted (IPTW) regression to examine 30-day mortality and microbiological recurrence. Pre-specified sensitivity analyses addressed calendar period, carbapenemase class and incomplete outcome ascertainment. Klebsiella pneumoniae accounted for 92.5% of isolates, MBL determinants for 44.1% and dual carbapenemases for 31.8%. Thirty-day mortality was 72% among 275 patients with documented day-30 status. Vasopressor requirement, viral pneumonia and bacterial respiratory infection were independently associated with death, whereas definitive ceftazidime/avibactam with or without aztreonam (C/AVI ± AZT) was associated with lower mortality (adjusted OR 0.38; 95% CI 0.17-0.83). Mortality was 66.3% with C/AVI ± AZT, 79.3% with colistin and 67.1% with other regimens. After IPTW, C/AVI ± AZT was associated with lower 30-day mortality than colistin (OR 0.48; 95% CI 0.26-0.93); in the OXA-48/KPC subgroup, the estimate was unchanged but less precise (OR 0.49; 95% CI 0.20-1.19). The association was attenuated and no longer significant after adjustment for calendar period (OR 0.72; 95% CI 0.37-1.42), with epoch-stratified estimates of 1.14, 0.75 and 0.44 for 2020-2021, 2022-2023 and 2024-2025, respectively; crude mortality under colistin was stable across epochs (81.1%, 76.6%, and 81.2%, respectively), whereas mortality under C/AVI ± AZT fell (83.3%, 72.2%, and 60.7%, respectively). Weighted estimates were near-identical in isolates with and without an MBL determinant (0.46 and 0.48, respectively). Recurrence (10.1%) was more frequent with single OXA-48 or MBL producers. C/AVI ± AZT was associated with lower 30-day mortality than colistin, but the association was concentrated in the period when the agent was routinely available and did not survive adjustment for calendar time. These findings describe an association, not a causal survival advantage.