Effectiveness and tolerability of intravenous fosfomycin in treating complicated urinary tract infections caused by Escherichia coli: a prospective cohort study from the FOSFOMIC project

Objectives: The FOSFOMIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli, in comparison with other intravenous antimicrobials. Methods: A prospective, multinational matched cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in ten centres from Spain, Italy, and Türkiye. Matching criteria included type of infection acquisition, Charlson and Pitt scores. Endpoints were clinical and microbiological cure, mortality, recurrence, and adverse effects. Analyses used conditional logistic regression and desirability of outcome ranking (DOOR). Results: Overall, 155 matched pairs were included. Clinical and microbiological cure rates were 65.2% (101/155; 95% CI, 57.4–72.2) and 63.2% (98/155; 95% CI, 55.4–70.4) with fosfomycin and comparators, respectively (adjusted OR, 1.09; 95% CI, 0.68–1.73; p 0.73). Mortality rates were 1.9% (3/155; 95% CI, 0.7–5.5) and 5.8% (9/155; 95% CI, 3.1–10.7), respectively (p 0.11). Recurrence rates were 14.2% (22/155; 95% CI, 9.6–20.6) in the fosfomycin group vs. 10.3% (16/155; 95% CI, 6.1–16.1) (p 0.39). Severe adverse effects occurred in 1.9% (3/155; 95% CI, 0.7–5.5) of patients treated with fosfomycin vs. 0.6% (1/155; 95% CI, 0.0–3.3) in the control group (p 0.62). Non-severe adverse effects were more frequent with fosfomycin, affecting 23.3% (36/155; 95% CI, 17.0–30.7) compared with 7.7% (12/155; 95% CI, 4.1–13.1) in the control group (adjusted OR, 5.36; 95% CI, 2.04–14.1; p < 0.001). In DOOR analysis, fosfomycin demonstrated comparable effectiveness in treating pyelonephritis (probability of better DOOR, 54.0%; 95% CI, 48.5–59.6) and in comparison with ceftriaxone (50.3%; 95% CI, 44.7–55.8), without evidence of inferiority in bacteraemic urinary tract infections (DOOR, 47.3%; 95% CI, 41.7–52.8). Discussion: Fosfomycin is a viable option for treating cUTIs caused by E. coli, allowing for diversification in the treatment of these high-incidence infections.