Therapeutic challenges and emerging strategies against carbapenem-resistant Acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CRAB) remains a formidable clinical challenge, driven by limited therapeutic options and multifaceted resistance mechanisms. While current polypharmacy regimens require evidence-based refinement, several emerging antimicrobials offer renewed hope. Sulbactam-durlobactam has demonstrated superior clinical resolution in CRAB-induced pneumonia and meningitis compared to traditional polymyxin-based regimens. Eravacycline achieves 100% microbiological clearance in abdominal infections without promoting resistance, and cefiderocol retains activity against metallo-β-lactamase-producing strains in clinical settings. Beyond these, zosurabalpin targets LPS transport via a novel mechanism, while bacteriophage cocktails and engineered antimicrobial peptides are advancing through clinical validation. In this review, we comprehensively examine the heterogeneous resistance mechanisms underlying CRAB persistence and critically evaluate emerging antimicrobial-centered therapeutic paradigms, with emphasis on empirically validated strategies for managing invasive CRAB infections.