TY - JOUR
T1 - Fosfomycin Vs Ciprofloxacin as Oral Step-Down Treatment for Escherichia coli Febrile Urinary Tract Infections in Women
T2 - A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial
AU - Ten Doesschate, Thijs
AU - Kuiper, Sander
AU - van Nieuwkoop, Cees
AU - Hassing, Robert-Jan
AU - Ketels, Tom
AU - van Mens, Suzan P
AU - van den Bijllaardt, Wouter
AU - van der Bij, Akke K
AU - Geerlings, Suzanne E
AU - Koster, Ad
AU - Koldewijn, Evert L
AU - Branger, Judith
AU - Hoepelman, Andy I M
AU - van Werkhoven, Cornelis H
AU - Bonten, Marc J M
AU - FORECAST study team
N1 - © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2022/8/25
Y1 - 2022/8/25
N2 - 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 Trialregister.nl (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.Fosfomycin is noninferior to ciprofloxacin regarding clinical cure as a targeted oral step-down treatment for Escherichia colifebrile urinary tract infections in women. Its use could prevent extended hospitalization in cases of resistance, intolerance, or allergies to existing step-down antibiotics.
AB - 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 Trialregister.nl (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.Fosfomycin is noninferior to ciprofloxacin regarding clinical cure as a targeted oral step-down treatment for Escherichia colifebrile urinary tract infections in women. Its use could prevent extended hospitalization in cases of resistance, intolerance, or allergies to existing step-down antibiotics.
KW - Escherichia coli
KW - PYELONEPHRITIS
KW - antimicrobial resistance
KW - fosfomycin
KW - urinary tract infection
U2 - 10.1093/cid/ciab934
DO - 10.1093/cid/ciab934
M3 - Article
C2 - 34791074
SN - 1058-4838
VL - 75
SP - 221
EP - 229
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 2
ER -