• Therapeutic Landscape Evolution : Current FDA-approved triple regimens feature sulbactam-durlobactam (SUL-DUR), the siderophore cephalosporin cefiderocol (FDC), and eravacycline. Zosurabalpin remains in Phase I evaluation, while Acinetobacter baumannii prophylactic vaccines are still undergoing preclinical development. • CRAB Treatment Paradigms : SUL-DUR combination therapy emerges as a promising first-line therapeutic candidate for critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections. FDC demonstrates pivotal potential in multidrug-resistant pathogen co-therapy frameworks through its innovative iron-transport mechanism. • Strategic Interventions : Dual-track approaches are imperative: 1) Accelerating CRAB-targeted drug development through priority review pathways, implementing adaptive clinical trial designs, and establishing dynamic risk management-based post-marketing surveillance systems; 2) Strengthening institutional infection control protocols and refining antimicrobial stewardship programs to curb CRAB dissemination. 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.
Yang et al. (2026) studied this question.