Fosfomycin for Urinary Tract Infections
Direct Recommendation
For uncomplicated cystitis in women, use a single 3-gram oral dose of fosfomycin tromethamine; for complicated UTIs, fosfomycin is NOT recommended as first-line therapy, but may be considered as salvage therapy using 3 grams orally every 48-72 hours for 3 total doses when other agents have failed. 1, 2
Uncomplicated Cystitis (First-Line Use)
Standard Dosing
- Single 3-gram oral dose is the FDA-approved regimen for uncomplicated UTI (acute cystitis) in women 18 years and older 2
- Mix the granules with water before ingesting; never take in dry form 2
- May be taken with or without food 2
- Provides therapeutic urinary concentrations for 24-48 hours 1, 3
Guideline Support
- The American Urological Association recommends fosfomycin as one of three first-line therapies for uncomplicated UTIs (Grade B evidence) 3
- The European Association of Urology lists fosfomycin as a first-line option, with comparable clinical efficacy to nitrofurantoin but with single-dose convenience 3
- Clinical and bacteriological cure rates of 75-90% at 5-11 days post-therapy, with 62-93% eradication at 4-6 weeks 4
Key Advantages
- Single-dose regimen improves adherence compared to 3-7 day courses 3
- Minimal collateral damage to intestinal flora 3
- Safe in pregnancy for asymptomatic bacteriuria 3
- Effective against multidrug-resistant pathogens including ESBL-producing organisms and VRE 3, 5
Complicated UTIs (Restricted Use)
Critical Restrictions
The American College of Physicians and European Association of Urology explicitly state that fosfomycin is NOT recommended for complicated UTIs or pyelonephritis due to insufficient efficacy data. 1, 6
When to Avoid Single-Dose Fosfomycin
- Never use for pyelonephritis - insufficient efficacy data 1, 3
- Not first-line for complicated UTIs - single-dose achieves therapeutic concentrations for only 24-48 hours, which is inadequate 1
- Not recommended for men with UTIs - limited clinical efficacy data in this population 3
- Do not use for non-fermenting gram-negative rods (e.g., Pseudomonas) - lacks sufficient data and has poor efficacy 6
Salvage Therapy Exception (Off-Label)
The Infectious Diseases Society of America suggests considering a multi-dose regimen for complicated lower UTIs when first-line agents have failed: 1
- Dosing: 3 grams orally every 48-72 hours for a total of 3 doses
- Indications: Previous treatment failure, multidrug-resistant pathogens, or intolerance to first-line agents 7
- Evidence quality: Lower-quality evidence; this is a weak recommendation 1
Intravenous Fosfomycin for Complicated Upper UTI
- Dosing: 6 grams IV every 8 hours for 7 days (14 days if concurrent bacteremia) 1, 7
- Based on the ZEUS trial showing superiority over piperacillin-tazobactam for complicated upper UTIs 1, 7
- Particularly effective against ESBL-producing organisms, carbapenem-resistant Enterobacterales, and MDR gram-negatives 7
- Limitation: Not widely available in many countries 1
Special Populations and Pathogens
Multidrug-Resistant Organisms
- ESBL-producing E. coli: 96% susceptibility rate; fosfomycin is the most reliable oral option after carbapenems 5
- Vancomycin-resistant Enterococcus (VRE): 81% susceptibility; single 3-gram dose for uncomplicated UTI 3, 5
- Carbapenem-resistant Enterobacterales: May consider fosfomycin, though specific dosing for complicated UTI not established 1
Pregnancy
- Safe for use in pregnancy 3
- Recommended for asymptomatic bacteriuria in pregnant women as standard short-course or single-dose treatment 3
Men
- Not recommended for routine use due to limited clinical efficacy data 3
Monitoring and Follow-Up
When to Reassess
- If symptoms do not resolve by end of treatment or recur within 2 weeks, obtain urine culture and antimicrobial susceptibility testing 1, 3
- Routine post-treatment cultures are NOT indicated for asymptomatic patients 3
Adverse Effects
- Most common: diarrhea, nausea, and vomiting - generally mild and self-limiting 1, 4
- Transient gastrointestinal symptoms occur but are well-tolerated 4
Guideline-Recommended Alternatives for Complicated UTI
When fosfomycin is inappropriate for complicated UTI, the Infectious Diseases Society of America strongly recommends: 1
- Ceftazidime-avibactam
- Meropenem-vaborbactam
- Aminoglycosides (moderate-certainty evidence, though nephrotoxicity risk increases after 7 days) 6
- Carbapenems for susceptible isolates 6
Critical Pitfalls Summary
- Never use single-dose oral fosfomycin for pyelonephritis - inadequate duration of therapeutic concentrations 1
- Do not use as first-line for complicated UTIs - reserve for salvage therapy only 1
- Avoid in non-fermenting organisms (Pseudomonas, Acinetobacter) - poor efficacy 6
- Do not routinely use in men - insufficient efficacy data 3
- Do not treat asymptomatic bacteriuria except in pregnant women or before urological procedures 3