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Background: Increasing incidence of carbapenem-resistant Gram-negative bacteraemia (CR-GNB) has triggered increased use of polymyxins, likely fuelling the emergence and spread of colistin resistance., Aim: To estimate the excess clinical burden of colistin resistance in intensive care patients with CR-GNB., Methods: A cohort of patients with CR-GNB during their stay in the intensive care unit (ICU) of a university hospital in Greece over a 4-year period (2020-2023) was constructed. Competing risks survival analysis was performed to estimate the burden associated with colistin resistance., Findings: Of the 177 ICU patients with CR-GNB, 134 (76%) had colistin-resistant isolates, predominantly Acinetobacter baumannii (79%), identified by broth microdilution. Patients with colistin-resistant infection were similar to those with colistin-susceptible infection with respect to age, sex, APACHE II score, Charlson comorbidity index score, Pitt bacteraemia score, prior surgery and the occurrence of polymicrobial cultures. However, patients in the colistin-resistant group had lower risk of mortality compared with those in the colistin-susceptible group (31% vs 44%, P = 0.004 at 14 days, respectively; 46% vs 56% at 28 days, respectively; P = 0.173). Multi-variable regression analysis confirmed that colistin-resistant CR-GNB was associated with significantly lower risk of inpatient death compared with colistin-susceptible CR-GNB within 14 days [cause-specific hazard ratio (csHR) 0.53, 95% CI 0.28-1.01) and 28 days (csHR 0.55, 95% CI 0.31-0.95) of infection onset., Conclusion: Limited impact of colistin resistance on mortality was demonstrated in a large contemporary cohort of ICU patients with CR-GNB, possibly reflecting the recent shift away from colistin-based treatment regimens., (Copyright © 2024 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Acinetobacter baumannii has emerged as a pressing challenge in clinical practice, mainly due to the development of resistance to multiple antibiotics, including colistin, one of the last-resort treatments. This review highlights all the possible mechanisms of colistin resistance and the genetic basis contributing to this resistance, such as modifications to lipopolysaccharide or lipid A structures, alterations in outer membrane permeability via porins and heteroresistance. In light of this escalating threat, the review also evaluates available treatment options. The development of new antibiotics (cefiderocol, sulbactam/durlobactam) although not available everywhere, and the use of various combinations and synergistic drug combinations (including two or more of the following: a polymyxin, ampicillin/sulbactam, carbapenems, fosfomycin, tigecycline/minocycline, a rifamycin, and aminoglycosides) are discussed in the context of overcoming colistin resistance of A. baumannii infections. Although most studied combinations are polymyxin-based combinations, non-polymyxin-based combinations have been emerging as promising options. However, clinical data remain limited and continued investigation is essential to determine optimal therapeutic strategies against colistin-resistant A. baumannii .