6/28/23, 10:40 PM FOREST Pathway Feedback Search Clinical Topics Home Studies FOREST FOREST Disease Disease Disease Acute cystitis Acute pyelonephritis Recurre Trial question Is fosfomycin noninferior to ceftriaxone or meropenem in patients with bacteremic UTI due to multidrug-resistant E. coli? Study design Multi-center Open label RCT Population Characteristics of study participants 51.0% female N = 143 49.0% male 143 patients (73 female, 70 male) Inclusion criteria: adult patients with bacteremic UTIs due to multidrug-resistant E. coli Key exclusion criteria: septic shock, prostatitis; kidney transplantation; polycystic kidney disease; > 48 hours delay in abscess drainage or obstruction release; palliative care; liver cirrhosis; hemodialysis; allergy to study drugs; active empirical treatment > 72 hours at randomization Interventions N=70 fosfomycin (an intravenous dose of 4 g every 6 hours with an option to switch to oral dose after 4 days) N=73 comparator antibiotics (intravenous ceftriaxone 1 g daily or meropenem 1 g every 8 hours, could switch to an oral agent or IV ertapenem after 4 days) Primary outcome https://web.pathway.md/studies/recCPJqdZcTJ8yZaT 1/2 6/28/23, 10:40 PM FOREST Pathway Rate of clinical and microbiological cure 5 to 7 days after administration 78.1 % 78.1 68.6 58.6 % 39.0 % Difference exceeding nonferiority margin 19.5 % 0.0 % Fosfomycin Comparator antibiotics Difference exceeding nonferiority margin in the rate of clinical and microbiological cure 5 to 7 days after administration (68.6% vs. 78.1%; ARD -9.4, 95% CI -21.5 to Infinity) Secondary outcomes No significant difference in clinical or microbiological failure (14.3% vs. 19.7%; ARD -5.4, 95% CI -Infinity to 4.9) No significant difference in death at day 30 (3.2% vs. 2.8%; AD 0.4%, 95% CI -Infinity to 5.2) No significant difference in relapse (13.1% vs. 8.4%; AD 4.7%, 95% CI -Infinity to 13.5) Safety outcomes No significant difference in adverse events and serious adverse events. Significant difference in adverse event-related discontinuations (8.5% vs. 0%). Conclusion In adult patients with bacteremic UTIs due to multidrug-resistant E. coli, fosfomycin was not noninferior to comparator antibiotics with respect to the rate of clinical and microbiological cure 5 to 7 days after administration. Reference Jes s Sojo-Dorado, Inmaculada L pez-Hern ndez, Clara Rosso-Fernandez et al. Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2137277. Open reference URL https://web.pathway.md/studies/recCPJqdZcTJ8yZaT 2/2