Carbapenem-Resistant Acinetobacter baumannii: Treatment, PK/PD Considerations, and Emerging Strategies

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical-priority pathogen associated with severe healthcare-associated infections, limited therapeutic options, and high mortality, particularly among critically ill patients. This narrative review summarises current and emerging therapeutic strategies for CRAB infections, with particular emphasis on pharmacokinetic/pharmacodynamic (PK/PD) considerations and antimicrobial exposure at different sites of infection. Sulbactam-containing regimens remain central to CRAB treatment, with sulbactam–durlobactam recommended by the 2026 Infectious Diseases Society of America (IDSA) guidance in combination with imipenem–cilastatin or meropenem for invasive CRAB infection, with definitive selection informed by susceptibility results and infection site. High-dose ampicillin–sulbactam, cefiderocol, polymyxins, and tetracycline derivatives retain important but context-dependent roles, while adequate source control remains essential. Importantly, antimicrobial susceptibility alone may not predict therapeutic success, particularly at sites where adequate drug exposure is difficult to achieve. Infection-site pharmacokinetics are therefore discussed to support rational treatment selection in pulmonary, bloodstream, urinary, central nervous system, and deep-seated infections. Emerging agents, including zosurabalpin, apramycin, zifanocycline, and next-generation polymyxins, may expand future treatment options. Nebulised antibiotics, bacteriophages, vaccines, and monoclonal antibodies represent additional evolving strategies, although robust evidence of clinical benefit remains limited. Optimizing CRAB therapy requires integration of susceptibility data, PK/PD principles, infection-site drug exposure, toxicity, and effective source control.