Objective: The purpose of this study was to determine the place in therapy of intravenous (IV) fosfomycin (Contepo) for the new Food and Drug Administration (FDA)-approved indication of complicated urinary tract infection (cUTI). Data Sources: ClinicalTrials.gov and PubMed (through 11/2025). Study Selection and Data Extraction: Data sources were searched and filtered to identify randomized controlled trials (RCTs) studying IV fosfomycin in cUTIs. Two primary phase III trials evaluating IV fosfomycin in cUTI were identified and analyzed. Additional ancillary studies were selected to contextualize primary studies. Data Synthesis: The ZEUS trial showed IV fosfomycin was noninferior to piperacillin-tazobactam (PIP-TAZ) in cUTI/acute pyelonephritis (AP), with similar results between cUTI, AP, and extended spectrum beta-lactamase (ESBL) subgroups. The FOREST trial showed fosfomycin did not meet noninferiority to comparators (ceftriaxone, meropenem) in multi-drug resistant (MDR) bacteremia with urinary source and had more treatment-limiting adverse effects that prevented attainment of the primary endpoint. Clinical practice guidelines were referenced to compare IV fosfomycin to existing antibiotic recommendations. Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Intravenous fosfomycin is a promising carbapenem- and fluoroquinolone-sparing therapy in cUTI/AP. It is an efficacious option empirically or as a targeted therapy. The best case to support the use of IV fosfomycin may be in ESBL-producing, non-bacteremic cUTI/AP, in hemodynamically stable patients. Conclusion: Intravenous fosfomycin is a newly approved antibiotic formulation in the United States that may have a role in preventing the emergence of drug-resistant cUTI.
Nuss et al. (2026) studied this question.