Fosfomycin Vs Ciprofloxacin as Oral Step-Down Treatment for Escherichia coli Febrile Urinary Tract Infections in Women: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial

Clin Infect Dis. 2022 Aug 25;75(2):221-229. doi: 10.1093/cid/ciab934.


Background: We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women.

Methods: This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2-5 days of empirical intravenous antimicrobials for E. coli fUTI were assigned to step-down treatment with once-daily 3g fosfomycin or twice-daily 0.5g ciprofloxacin for 10 days of total antibiotic treatment. For the primary end point, clinical cure at days 6-10 post-end of treatment (PET), a noninferiority margin of 10% was chosen. The trial was registered on (NTR6449).

Results: After enrollment of 97 patients between 2017 and 2020, the trial ended prematurely because of the coronavirus disease 2019 pandemic. The primary end point was met in 36 of 48 patients (75.0%) assigned to fosfomycin and 30 of 46 patients (65.2%) assigned to ciprofloxacin (risk difference [RD], 9.6%; 95% confidence interval [CI]: -8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at days 6-10 PET occurred in 29 of 37 (78.4%) and 33 of 35 (94.3%; RD, -16.2%; 95% CI: -32.7 to -0.0%). Any gastrointestinal adverse event was reported in 25 of 48 (52.1%) and 14 of 46 (30.4%) patients (RD, 20.8%; 95% CI: 1.6% to 40.0%), respectively.

Conclusions: Fosfomycin is noninferior to ciprofloxacin as oral step-down treatment for fUTI caused by E. coli in women. Fosfomycin use is associated with more gastrointestinal events.

Clinical trial registration: Trial NL6275 (NTR6449).

Keywords: Escherichia coli; antimicrobial resistance; fosfomycin; urinary tract infection.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Bacterial Agents / adverse effects
  • COVID-19*
  • Ciprofloxacin / therapeutic use
  • Double-Blind Method
  • Escherichia coli
  • Escherichia coli Infections* / complications
  • Escherichia coli Infections* / drug therapy
  • Female
  • Fever / drug therapy
  • Fosfomycin* / adverse effects
  • Humans
  • Urinary Tract Infections* / microbiology


  • Anti-Bacterial Agents
  • Fosfomycin
  • Ciprofloxacin

Associated data

  • NTR/NL6275
  • NTR/NTR6449