"Effectiveness and tolerability of intravenous fosfomycin in treating complicated urinary tract infections caused by Escherichia coli: A prospective cohort study from the FOSFO-MIC Project".

Objectives: The FOSFO-MIC 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 10 centres from Spain, Italy, and Türkiye. Matching criteria included healthcare-relation, Charlson and Pitt scores. Endpoints were clinical and microbiological cure, mortality, recurrence, and adverse effects. Analyses used conditional logistic regression and 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 to 63.2% (98/155; 95% CI:55.4-70.4) with fosfomycin and comparators, respectively (aOR: 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 versus 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 versus 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 to 7.7% (12/155; 95% CI: 4.1-13.1) in the control group (aOR: 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 to ceftriaxone (50.3%; 95% CI: 44.7-55.8), without evidence of inferiority in bacteraemic UTIs (DOOR: 47.3%; 95% CI: 41.7-52.8).

Conclusions: Fosfomycin is a viable option for treating cUTIs caused by E. coli, allowing for diversification in the treatment of these high-incidence infections.