Fosfomycin for E. coli Urinary Tract Infections
Fosfomycin is FDA-approved and guideline-recommended as a first-line treatment for uncomplicated urinary tract infections caused by E. coli in women, administered as a single 3-gram oral dose. 1
FDA-Approved Indication and Dosing
- Fosfomycin tromethamine is specifically indicated for uncomplicated urinary tract infections (acute cystitis) in women caused by susceptible strains of E. coli and Enterococcus faecalis. 1
- The recommended dosage is one sachet (3 grams) of fosfomycin tromethamine granules mixed with water, taken as a single dose with or without food. 1
- This single dose achieves therapeutic urinary concentrations of approximately 706 mcg/mL within 2-4 hours, maintaining concentrations above 100 mcg/mL for 26 hours. 1
Guideline Recommendations
- The European Association of Urology (2024) lists fosfomycin trometamol as a first-line treatment option for uncomplicated cystitis in women, with comparable clinical efficacy to other first-line agents and the advantage of single-dose administration. 2, 3
- The American Urological Association recommends fosfomycin as one of three first-line therapies for uncomplicated UTIs with strong recommendation (Grade B evidence). 3
- While bacterial eradication rates are somewhat lower than some comparators (approximately 80% vs 93% for nitrofurantoin), clinical efficacy is comparable with the convenience of single-dose therapy and minimal collateral damage to intestinal flora. 3
Clinical Efficacy Against E. coli
- Fosfomycin demonstrates excellent in vitro activity against E. coli, with 99.6% susceptibility rates among US isolates, significantly higher than ciprofloxacin (65.4%), levofloxacin (65.8%), or trimethoprim-sulfamethoxazole (59.9%). 4
- Clinical success rates for physician-diagnosed UTIs range from 74.8% to 89.9% depending on diagnostic criteria used. 5
- Fosfomycin maintains excellent activity against multidrug-resistant E. coli, including ESBL-producing strains, with all 100 randomly selected ESBL-producing E. coli isolates showing susceptibility. 5
Important Limitations and Contraindications
- Fosfomycin is NOT indicated for pyelonephritis or perinephric abscess. 1
- Fosfomycin is NOT recommended for routine use in men with UTIs due to limited efficacy data in this population. 3
- If bacteriuria persists or reappears after fosfomycin treatment, alternative therapeutic agents should be selected. 1
- Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients. 2, 3
When to Perform Follow-up Testing
- For women whose symptoms do not resolve by the end of treatment or recur within 2 weeks, perform urine culture and antimicrobial susceptibility testing. 2
- In these cases, assume the organism is not susceptible to fosfomycin and retreat with a 7-day regimen using another agent. 2
Special Populations
- For pregnant women with asymptomatic bacteriuria, fosfomycin is recommended as standard short-course treatment or single-dose therapy. 2, 3
- Fosfomycin is safe in pregnancy and does not require dosage adjustment in elderly patients or those with renal or hepatic impairment. 3, 6
Adverse Effects
- The most commonly reported adverse events are gastrointestinal disturbances including diarrhea, nausea, and vomiting, which are generally mild. 3, 7
- Recurrent infections occur in approximately 4.3% of cases. 5
Pharmacokinetic Advantages
- Fosfomycin has minimal propensity for collateral damage to intestinal flora compared to other antibiotics, resulting in minimal disruption to the gut microbiome. 3
- The single-dose convenience improves adherence compared to 3-7 day regimens. 3
- Approximately 38% of the dose is recovered unchanged in urine, with no plasma protein binding. 1