Fosfomycin Dosing for Urinary Tract Infections
For uncomplicated UTIs in women, administer a single 3-gram oral dose of fosfomycin tromethamine, which is the FDA-approved regimen and recommended by multiple international guidelines. 1, 2
Standard Dosing by Clinical Scenario
Uncomplicated Cystitis in Women
- Single 3-gram oral dose is the standard treatment 1, 2
- Mix the granules with water before ingesting; never take in dry form 1
- Can be taken with or without food 1
- Provides therapeutic urinary concentrations for 24-48 hours 2
- This regimen is endorsed by the European Association of Urology, American Urological Association (Grade B evidence), and Infectious Diseases Society of America 2
VRE-Associated Uncomplicated UTI
- Single 3-gram oral dose is recommended, identical to standard uncomplicated UTI dosing 3, 2
- This represents a weak recommendation with very low quality evidence, but fosfomycin remains one of the few oral options for VRE 3
Complicated Lower UTI (Off-Label)
- 3 grams orally every 48-72 hours for 3 total doses has been used off-label 4
- Reserve this regimen for patients who have failed first-line therapy, are infected with multidrug-resistant pathogens, or cannot tolerate standard agents 4
- Important caveat: European guidelines explicitly restrict fosfomycin to uncomplicated cystitis only and do not recommend it for complicated UTIs 5
Complicated Upper UTI/Pyelonephritis
- Intravenous fosfomycin 6 grams every 8 hours for 7 days (14 days if concurrent bacteremia) showed efficacy in the ZEUS trial 4
- Oral fosfomycin should NOT be used for pyelonephritis or complicated upper UTIs due to insufficient efficacy data 2, 5
- IV formulation demonstrated superiority over piperacillin-tazobactam specifically for complicated upper UTI caused by resistant Enterobacterales 4
Critical Clinical Considerations
When Fosfomycin IS Appropriate
- Uncomplicated cystitis in women caused by E. coli, Enterococcus (including VRE), or other typical uropathogens 2, 5
- ESBL-producing Enterobacteriaceae causing uncomplicated lower UTI only 5
- Asymptomatic bacteriuria in pregnant women (single 3-gram dose or standard short-course) 2
When Fosfomycin Should NOT Be Used
- Pyelonephritis - use fluoroquinolones or cephalosporins instead 2
- Complicated UTIs - insufficient data per European guidelines 2, 5
- Men with UTIs - limited efficacy data in this population 2
- Non-fermenting gram-negative rods (e.g., Pseudomonas) - lacks efficacy data and should not be used 5
Important Pitfalls to Avoid
Pharmacokinetic Variability
- High interindividual variability exists in urinary fosfomycin concentrations 6
- While 100% of patients maintain concentrations above MIC for 24 hours, only 67.5% do so at 48 hours and 30% at 72 hours 6
- High urinary output is associated with lower urinary concentrations and reduced drug exposure 6
Adverse Effects
- Gastrointestinal disturbances (diarrhea, nausea, vomiting) are most common 2, 7
- Adverse events may be more frequent with fosfomycin compared to nitrofurantoin, though generally mild 7, 8
- Single-dose therapy shows higher initial adverse event rates (43% at day 4) compared to multi-day regimens, but rates equalize by day 9 8
Follow-Up Considerations
- Routine post-treatment urinalysis or cultures are NOT indicated for asymptomatic patients 2
- If symptoms persist at end of treatment or recur within 2 weeks, perform urine culture and susceptibility testing 2
Comparative Efficacy
Fosfomycin demonstrates comparable clinical and microbiological cure rates to nitrofurantoin, ciprofloxacin, norfloxacin, and cotrimoxazole for uncomplicated UTIs 7, 9. The primary advantage is single-dose convenience, which improves adherence and causes minimal collateral damage to intestinal flora 2, 9. Clinical efficacy remains high despite somewhat lower bacteriological efficacy compared to some first-line agents 2.