This review discusses emerging in vitro and in vivo strategies for the control of Acinetobacter baumannii, a critical multidrug-resistant pathogen; the increasing isolation of strains resistant to multiple drugs, including newly developed and last-resort antibiotics, has highlighted the urgent need to pursue adjunctive therapeutic technologies. The article aims to provide an overview of alternative control approaches beyond conventional antibiotics. Emphasis is placed on strategies based on the disruption of essential metabolic pathways, nanotechnology-based approaches such as antibiotic-coated nanoparticles, in vivo bacteriophage therapy, and drug repurposing, specifically compounds such as selective serotonin reuptake inhibitors (SSRIs), as a means of exploiting already approved pharmaceuticals. By synthesizing recent findings, this review highlights current advances in the development of innovative therapeutic strategies against A. baumannii infections.

Acinetobacter baumannii is a microorganism of major global clinical importance, whose carbapenem-resistant phenotype is considered a priority target for the development of new antimicrobial agents. Carbapenem-resistant A. baumannii is associated with healthcare-associated infections and exhibits high mortality rates, prolonged hospital stays, and extensive use of intensive care units. As a control strategy, green-synthesized silver nanoparticles have gained increasing attention. Based on this, the aim of this study was to synthesize a novel triphasic silver nanocomposite, characterize it, and evaluate its antibacterial activity against extensively drug-resistant and pan-drug-resistant isolates. The nanocomposite was synthesized using cell-free bacterial supernatant and was physicochemically characterized regarding concentration, size, morphology, and crystallinity. Its antibacterial activity was assessed using broth microdilution and time–kill assays, followed by toxicity assays using human erythrocytes. A nanoscale and stable nanocomposite was obtained and was composed of metallic silver, silver chloride, and silver phosphate, which exhibited antibacterial activity against all tested isolates. In the toxicity assay, the nanocomposite demonstrated low toxicity and a high selectivity index. These findings demonstrate that Ag/AgCl/Ag₃PO₄ nanocomposite exhibits strong activity against resistant phenotypes for which therapeutic options are limited, highlighting its potential as a control strategy against this pathogen.