Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli : a post hoc analysis of the FOREST randomized trial

Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P=0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P=0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P=0.75). No relevant differences in adverse events were seen. Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.