Intravenous Fosfomycin for Gram-Negative and Gram-Positive Bacterial Infections: A Systematic Review of the Clinical Evidence.

Background: The increasing worldwide problem of bacterial infections caused by multidrug-resistant Gram-negative and Gram-positive pathogens has led to consideration of intravenous fosfomycin, especially in combination antimicrobial regimens. We performed a systematic review of the evidence from comparative and non-comparative studies of patients who received intravenous fosfomycin as monotherapy or in combination with other antibiotics. Methods: Relevant studies were sought in six resources (Cochrane Library, Google Scholar, PubMed Central, PubMed, Scopus, and Web of Science) and two registries [ClinicalTrials.gov and International Clinical Trials Registry Portal (ICTRP)]. Results: Of the 2351 screened articles, 53 (31 comparative and 22 non-comparative studies) reported relevant data for patients with infections at various sites caused by Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, and Gram-positive bacteria, including Staphylococcus spp. and enterococci. Intravenous fosfomycin, either as monotherapy or combination therapy, showed similar or, in some studies, better efficacy (clinical and microbiological cure) compared to therapy with antimicrobial agents not including fosfomycin. The data evaluated also suggest that intravenous fosfomycin has a good safety profile. The administration of the antibiotic may be associated with electrolyte imbalances, especially hypokalemia and hypernatremia. These adverse events may be prevented and controlled with appropriate therapeutic measures and rarely lead to the discontinuation of the drug. Conclusions: Overall, the considerable body of published data suggests that intravenous fosfomycin is safe and effective. The antibiotic may be considered for patients with both Gram-positive and Gram-negative infections, especially in critically ill patients and/or deep-seated infections. The heterogeneity of the included studies is a limitation that prevents firm conclusions.