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Peer-reviewedCC BY 4.0Infection

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

  1. 1Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties G D’Alessandro, University of Palermo, Palermo, 90133 Italy
  2. 2Infectious and Tropical Disease Unit, AOU Policlinico P. Giaccone, Palermo, 90127 Italy

Abstract

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.

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BibTeX
@article{pipito2026fosfomycin,
  title = {{Fosfomycin as an adjunctive agent against carbapenem-resistant Acinetobacter baumannii: an updated narrative review}},
  author = {Luca Pipitò and Eleonora Bono and Chiara Vincenza Mazzola and Antonio Cascio},
  journal = {Infection},
  year = {2026},
  month = jul,
  doi = {10.1007/s15010-026-02895-8},
  url = {https://doi.org/10.1007/s15010-026-02895-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Fosfomycin as an adjunctive agent against carbapenem-resistant Acinetobacter baumannii: an updated narrative review
AU  - Luca Pipitò
AU  - Eleonora Bono
AU  - Chiara Vincenza Mazzola
AU  - Antonio Cascio
PY  - 2026
DA  - 2026/07/27
JO  - Infection
DO  - 10.1007/s15010-026-02895-8
UR  - https://doi.org/10.1007/s15010-026-02895-8
AB  - 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.
SN  - 0300-8126
SN  - 1439-0973
ER  -