Contemporary management of carbapenem-resistant Acinetobacter baumannii: resistance mechanisms, therapeutic advances, rapid diagnostics, and PK/PD-guided dosing

Carbapenem-resistant Acinetobacter baumannii (CRAB) remains a global health threat because of its environmental persistence, resistance mechanisms, and limited treatment options. Contemporary management requires integration of resistance biology, rapid diagnostics, susceptibility testing, and pharmacokinetic/pharmacodynamic (PK/PD) optimization. This narrative review synthesizes evidence on OXA-type carbapenemases, NDM, reduced membrane permeability, efflux-pump overexpression, heteroresistance, and antibiotic tolerance. In India and Southeast Asia, OXA-23-like enzymes remain predominant, whereas NDM occurs in subsets and may compromise durlobactam-containing regimens. Sulbactam-durlobactam combined with imipenem-cilastatin or meropenem is the preferred regimen for invasive CRAB when active and available. When unavailable, high-dose ampicillin-sulbactam with another active agent may be used as temporary bridging therapy. Cefiderocol, minocycline, tigecycline, and polymyxins have context-dependent roles guided by susceptibility, infection site, toxicity, and access. Evidence varies across agents, from randomized trials to observational, PK/PD, in vitro, and animal data. Because this narrative review used purposive rather than systematic study selection, without formal risk-of-bias or certainty assessment, the treatment hierarchy should be interpreted as a clinically oriented synthesis rather than a systematically derived ranking. Rapid diagnostics can shorten time to organism- and mechanism-informed treatment, but molecular findings require phenotypic confirmation. PK/PD-guided dosing and therapeutic drug monitoring may be useful in critically ill patients. By integrating rapidly evolving therapeutic evidence with resistance mechanisms, diagnostic limitations, PK/PD principles, and resource-dependent feasibility, this review provides a timely clinical framework that distinguishes established practice from emerging evidence and identifies uncertainties shaping contemporary CRAB management. Improved outcomes will also depend on stewardship, infection prevention, surveillance, and strategies for resource-limited settings.