Journal article
Daily fosfomycin versus levofloxacin for complicated urinary tract infections
mBio, Vol.14(5), e0167723
10/31/2023
DOI: 10.1128/mbio.01677-23
PMCID: PMC10783529
PMID: 37698412
Abstract
ABSTRACT Fosfomycin, approved in the United States only for cystitis, is an attractive alternative for oral treatment of outpatient complicated urinary tract infections (cUTIs) as it has antimicrobial activity against most common uropathogens. The study was a multicenter, randomized, open-label pragmatic superiority clinical trial evaluating the efficacy of oral fosfomycin versus oral levofloxacin strategies in cUTIs (FOCUS study). The trial compared two strategies for initial or step-down oral therapy of cUTI without bacteremia after 0–48 hours of parenteral antibiotic therapy. Subjects were assigned to 3 g of fosfomycin or 750 mg (or dose adjusted for kidney function) of levofloxacin daily for 5–7 days. Clinical and microbiological cures were assessed at the end of therapy (EOT) and test of cure (TOC) (approximately 21 days from the start of antibiotics). The trial did not meet accrual goals; thus, the results were descriptive. Only 51 subjects were included in the microbiological intention-to-treat population. The subjects were mainly females (76%), with a mean age of 46.7 years (standard deviation [SD] = 20.8) and acute pyelonephritis (88%). At the end of therapy, clinical cure remained similar (69% and 68% for fosfomycin and levofloxacin strategies, respectively), and microbiological success was 100% for both strategies. At the test of cure, clinical cure was similar (84% and 86% in the fosfomycin and levofloxacin strategies, respectively); however, a numerically lower microbiological success was observed for fosfomycin (69% compared to 84% for levofloxacin). These limited data suggest that fosfomycin could be an oral alternative as a step-down therapy for the treatment of cUTIs (registry number NCT 03697993). IMPORTANCE Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.
Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.
Details
- Title: Subtitle
- Daily fosfomycin versus levofloxacin for complicated urinary tract infections
- Creators
- Nadine Rouphael - Emory UniversityKarl Kreder - University of IowaPatricia Winokur - University of IowaElizabeth B. Takacs - University of IowaMichael C. Keefer - University of RochesterJessica Traenkner - Emory UniversityAna Drobeniuc - Emory UniversityYohei Doi - University of PittsburghSonal Munsiff - University of RochesterVance G. Fowler - Duke University HospitalScott Evans - Duke University HospitalRandolph E. Oler - Emmes (United States)Bonifride Tuyishimire - Emmes (United States)Marina Lee - National Institute of Allergy and Infectious DiseasesVarduhi Ghazaryan - National Institute of Allergy and Infectious DiseasesHenry F. Chambers - University of California, San FranciscoAnnette Esper - Emory UniversityPaulina A. Rebolledo - Emory UniversityZanthia Wiley - Emory UniversityJesse T. Jacob - Emory UniversityAneesh Mehta - Emory UniversityColleen S Kraft - Emory UniversityYun F Wang - Emory UniversityRody G. Bou Chaaya - Emory University School of MedicineDanielle Fayad - Emory UniversityAmer Bechnak - Emory UniversityHollie Macenczak - Emory UniversityAlexandra Dretler - Emory UniversityMichele Paine McCullough - Emory University School of MedicineSara Jo Johnson - Emory UniversityNour Beydoun - Emory UniversityYoussef Saklawi - Emory UniversityMark Mulligan - Emory UniversityGhina Alaaeddine - Emory UniversityCatherine Bunce - University of RochesterDwight Hardy - University of RochesterSusan Antenozzi - University of RochesterAndrew Moran - University of RochesterMalcolm Almuntazar-Harris - Emmes (United States)Alison Wall - Emmes (United States)John Sumerel - Emmes (United States)David Adler - University of RochesterMargaret Mueller - Northwestern MedicineDMID 15-0045 study group
- Contributors
- Robert A. Bonomo (Editor)
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.14(5), e0167723
- DOI
- 10.1128/mbio.01677-23
- PMID
- 37698412
- PMCID
- PMC10783529
- NLM abbreviation
- mBio
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Grant note
- DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: HHSN272201300018I; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: HHSN2722013000201; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: HHSN272201500002C; DOI: 10.13039/100000060, name: HHS | NIH | National Institute of Allergy and Infectious Diseases, award: UM1 AI104681
- Language
- English
- Electronic publication date
- 09/12/2023
- Date published
- 10/31/2023
- Academic Unit
- Infectious Diseases; Obstetrics and Gynecology; Urology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984472659302771
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