Fosfomycin as an adjunctive agent against carbapenem-resistant Acinetobacter baumannii: an updated narrative review

Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a critical therapeutic challenge due to limited effective treatment options and high associated mortality. Fosfomycin has been increasingly investigated as an adjunctive agent in combination regimens, despite its intrinsically reduced activity against A. baumannii. This narrative review summarizes current in vitro, in vivo, and clinical evidence on fosfomycin-containing therapies for CRAB infections. A total of 48 studies were included, encompassing in vitro (n = 27), animal (n = 2), and clinical investigations (n = 20). In one case, both in vitro and clinical data were reported. In vitro data suggest that fosfomycin may exhibit synergistic or additive activity when combined with several anti-CRAB agents, most consistently with sulbactam, imipenem, and colistin, although results are highly heterogeneous and method-dependent. Although limited, in vivo studies indicate improved bacterial clearance with fosfomycin-based combinations, particularly in pneumonia models. Clinical evidence remains largely observational and non-randomized, frequently involving critically ill patients receiving multiple combination therapies. While some multicenter studies, particularly from Italian cohorts, report improved clinical outcomes and survival associated with fosfomycin-containing regimens, especially in combination with cefiderocol, other studies do not confirm a clear benefit. Clinical trials have mainly demonstrated improvements in microbiological response and early infection control, without consistent effects on mortality. Overall, current evidence suggests that fosfomycin may provide additional benefit when incorporated into selected combination regimens for CRAB infections, although its independent contribution remains uncertain. Among the evaluated regimens, cefiderocol-fosfomycin combinations currently appear to be supported by the most encouraging observational clinical evidence, particularly regarding early clinical response and microbiological control.