Fosfomycin Dosing for Uncomplicated UTIs
For uncomplicated urinary tract infections in women, administer a single 3-gram oral dose of fosfomycin tromethamine, which is the FDA-approved regimen and provides therapeutic urinary concentrations for 24-48 hours. 1, 2
Standard Dosing Regimen
- Single dose: 3 grams orally, taken once 1, 2
- Mix the granules with water before ingesting; never take in dry form 1
- Can be taken with or without food 1
- This single-dose regimen maintains urinary concentrations above the EUCAST breakpoint (32 mg/L) in 100% of patients for 24 hours and 67.5% for 48 hours 3
Clinical Context and Efficacy
The single-dose fosfomycin regimen is specifically recommended for:
- Uncomplicated cystitis in women only - this is the primary FDA-approved indication 1, 2
- VRE-associated uncomplicated UTIs - same 3-gram single dose 4
- The European Association of Urology and American Urological Association both list fosfomycin as a first-line treatment option with comparable clinical efficacy to nitrofurantoin and other agents 2
Alternative Multi-Dose Regimens (Off-Label)
For complicated lower UTIs or treatment failures, research supports:
- 3 grams every 48-72 hours for a total of 3 doses 5, 6
- This off-label regimen is used when patients have failed first-line therapy, have MDR pathogens, or cannot tolerate standard treatments 5
- Pharmacokinetic modeling demonstrates that two 3-gram doses given 72 hours apart maintain urinary concentrations above 16 mg/L for 161 hours (66% efficacy time over 7 days) 6
Critical Limitations and Contraindications
Do NOT use fosfomycin for:
- Pyelonephritis - insufficient efficacy data; use fluoroquinolones or cephalosporins instead 2, 7
- Complicated UTIs - oral formulation lacks adequate data 2, 7
- Men with UTIs - limited clinical efficacy data in this population 2
- Non-fermenting gram-negative organisms (e.g., Pseudomonas, Acinetobacter) - fosfomycin is restricted to typical uropathogens only 7
Special Populations
- Pregnant women with asymptomatic bacteriuria: Single 3-gram dose is safe and recommended 2, 8
- Patients with renal insufficiency: Use with caution; elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients 2
- Cardiac insufficiency or hypernatremia: Exercise caution, particularly with IV formulations 2
Important Clinical Pitfalls
High interindividual variability exists in urinary fosfomycin concentrations - peak concentrations range from 1982 ± 1257 mg/L with recovery of only 44.5% after 48 hours 3. Patients with high urinary output achieve lower concentrations and reduced time above MIC, potentially leading to treatment failure 3.
If symptoms persist or recur within 2 weeks, obtain urine culture and antimicrobial susceptibility testing rather than empirically retreating 2. Routine post-treatment cultures are not indicated for asymptomatic patients 2.
Adverse Effects
The most common side effects are gastrointestinal:
- Diarrhea, nausea, and vomiting 2
- Generally mild and well-tolerated compared to multi-day regimens 8
- Lower risk of collateral damage to intestinal flora compared to other antibiotics 2
Intravenous Formulation (Not FDA-Approved in US)
For complicated upper UTIs with resistant organisms:
- 6 grams IV every 8 hours for 7 days (14 days if concurrent bacteremia) 5
- The ZEUS trial demonstrated superiority over piperacillin-tazobactam for complicated UTIs caused by ESBL-producing and carbapenem-resistant Enterobacterales 5
- This formulation is not available in the United States but is used in other countries 5