Oral fosfomycin after carbapenems as de-escalating therapy in complicated urinary tract infections: A randomized controlled trial.

OBJECTIVES

To determine whether oral fosfomycin trometamol is noninferior to carbapenem continuation as step-down therapy for cUTIs caused by third-generation cephalosporin-resistant Enterobacterales.

METHODS

In this open-label, randomized, noninferiority trial, adults with 3GCRE cUTIs who received 3 days of intravenous carbapenem were assigned to oral fosfomycin trometamol or continued carbapenem to complete 7 days. The primary outcome was day-7 clinical cure; secondary outcomes included day-28 clinical and microbiological cure, readmission, and length of stay.

RESULTS

A total of 124 participants were enrolled (62 per group). The mean age was 73 years, 62.1% were female, and Escherichia coli accounted for 91% of isolates. Clinical cure at day 7 occurred in 98.4% in both groups (risk difference 0.0; 95% CI, -0.04 to 0.04). Clinical cure at day 28 was also similar (91.9% in each group). Microbiological cure at day 7 was 100% with fosfomycin and 98.1% with carbapenem, and at day 28 was 90.3% and 85.5%, respectively. Hospital stay was shorter with fosfomycin (7.9 vs 12.0 days).

CONCLUSIONS

Oral fosfomycin trometamol as step-down therapy was comparable to continued carbapenem therapy for cUTIs caused by 3GCRE and significantly reduced hospital stay, supporting role of carbapenem-sparing option.