Abstract
Acinetobacter baumannii is a critical nosocomial pathogen recognized by the WHO as a top-priority threat due to its extensive drug resistance, particularly in carbapenem-resistant Acinetobacter baumannii (CRAB) strains. According to recent CDC reports, CRAB is one of the most urgent causes of hospital-acquired infections, driving longer hospital stays, higher costs, and mortality. This pathogen employs multiple resistance mechanisms, including efflux pumps, porins like OmpA, making it highly difficult to treat. Resistance is further shaped by β-lactamases, integrons, and mobile genetic elements. The emergence of MDR, XDR, and PDR strains signals the looming postantibiotic era, where conventional therapies are increasingly ineffective. While several reviews have provided in-depth analyses of individual mechanisms and some comprehensive overviews, this work provides a broad overview of resistance strategies and genetic determinants, including tet(A/B), cmlA, and mdfA. Importantly, we also highlight emerging alternatives such as novel emergent phage therapy (NEPT), which proactively counters antiphage resistance and nanoparticles (CNPs), which resensitize resistant isolates and enhance antibiotic efficacy. By combining mechanistic insights with emerging interventions, this review provides a comprehensive perspective on CRAB resistance and highlights research priorities for mitigating its global threat.