Intravenous Fosfomycin for Difficult-to-Treat Infections: A Real-Life Multicentric Study in Italy

Abstract

Background: Fosfomycin, an old antibiotic attracting renewed interest, offers a broad spectrum of activity and unique synergy with other agents. While widely used in severe infections, real-world data on intravenous fosfomycin remain limited. Objectives: This study aimed to describe the clinical and microbiological characteristics of patients treated with intravenous fosfomycin and to analyze its administration modalities in a real-world setting. Methods: A multicenter retrospective cohort study was conducted across five Italian hospitals. Adult patients receiving intravenous fosfomycin between January 2020 and December 2023 were included. Results: We enrolled 393 patients. The median age was 69 years, with most patients (45%) admitted to Critical Care Units. Pneumonia (34%), bloodstream infections (22%), and urinary tract infections (21%) were the most common indications. Gram-negative bacteria, particularly E. coli and P. aeruginosa, were the predominant pathogens. Fosfomycin was used as empirical therapy in 55% of cases and was combined with other agents in almost all cases (99%). The most frequent partners were piperacillin/tazobactam (21%) and new beta-lactam/beta-lactamase inhibitor combinations (18%). The median treatment duration was seven days, with most subjects (65%) receiving a fosfomycin dosage regimen of 16 g/day. Minimum inhibitory concentrations (MICs) values for fosfomycin were available for 61 isolates (15%), with 78.7% (48/61) showing MIC ≤ 32 mg/L. C. difficile infection occurred in only 2% of patients. Mortality rates at 30, 60, and 90 days were 21.6%, 26.7%, and 29.3%, respectively. Conclusions: This study provides valuable insights into the real-world use of intravenous fosfomycin.

Keywords: difficult-to-treat infections; intravenous fosfomycin; multidrug resistance.

Figure 1

Frequency of partner antibiotics administered with intravenous fosfomycin. BLICs* = Beta-Lactamase Inhibitor Combinations, such as ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam; Others**: oxacillin, cefazolin, fluoroquinolones, oritavancin, dalbavancin, and colistin.