Can fosfomycin (tromethamine) be used to treat an uncomplicated urinary tract infection (UTI) in an adult patient with normal renal function, and what is the recommended dosage?

Fosfomycin for Uncomplicated UTI

Yes, fosfomycin tromethamine is an appropriate first-line treatment for uncomplicated urinary tract infections (acute cystitis) in adult women, administered as a single 3-gram oral dose. 1, 2

Standard Dosing Regimen

• The FDA-approved dosage is one sachet (3 grams) of fosfomycin tromethamine granules mixed with water, taken as a single oral dose. 2
• The medication may be taken with or without food, but must never be taken in dry form—always mix with water before ingesting. 2
• This single dose provides therapeutic urinary concentrations (>128 mg/L) for 24-48 hours, which is sufficient to eradicate most uropathogens. 1, 3

Clinical Efficacy and Guideline Support

• The Infectious Diseases Society of America (IDSA), European Association of Urology (EAU), and American Urological Association (AUA) all recommend fosfomycin as first-line therapy for uncomplicated cystitis in women with an A-I evidence rating (strong recommendation, high-quality evidence). 1
• Clinical cure rates of 99% and bacteriological eradication rates of 75-90% at 5-11 days post-treatment have been demonstrated in clinical trials. 4
• Fosfomycin is particularly appropriate when trimethoprim-sulfamethoxazole resistance exceeds 20% in the community. 1

Key Advantages

• Single-dose administration eliminates compliance issues associated with 3-7 day regimens. 1, 5
• Minimal disruption to intestinal flora compared to fluoroquinolones and cephalosporins, reducing risk of C. difficile infection. 1
• Effective against multidrug-resistant pathogens including ESBL-producing E. coli, vancomycin-resistant Enterococcus (VRE), and MRSA. 1, 5
• Resistance rates remain remarkably low at only 2.6% in initial E. coli infections. 1
• Safe in pregnancy (Category B) and recommended for asymptomatic bacteriuria in pregnant women. 1, 3

Critical Limitations and Contraindications

• Fosfomycin should NOT be used for pyelonephritis, complicated UTIs, or upper urinary tract infections due to insufficient efficacy data. 1, 5
• Not recommended for routine use in men with UTIs due to limited clinical efficacy data in this population. 1
• Use with caution in patients with hypernatremia, cardiac insufficiency, or renal insufficiency (elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients). 1

Important Clinical Caveat from Recent Guidelines

• The 2024 WHO Expert Committee specifically excluded fosfomycin from their recommendations for lower UTIs, citing that randomized controlled trials showed nitrofurantoin (5 days) had significantly greater likelihood of clinical and microbiologic resolution at 28 days compared to single-dose fosfomycin. 6
• Cost was also a consideration, as fosfomycin is more expensive than nitrofurantoin. 6
• This represents a divergence from other major guidelines (IDSA, EAU, AUA), which continue to recommend fosfomycin as first-line therapy. 1

When Treatment Fails

• If symptoms do not resolve within 2-3 days or recur within 2 weeks, perform urine culture and antimicrobial susceptibility testing. 1
• Consider alternative agents: nitrofurantoin 100mg twice daily for 5 days, trimethoprim-sulfamethoxazole 160/800mg twice daily for 3 days, or fluoroquinolones for 3 days. 1, 5

Alternative Multi-Dose Regimen (Off-Label)

• For situations requiring longer treatment (not young women with simple cystitis), fosfomycin 3g on days 1,3, and 5 has been suggested, though this is off-label. 1, 7
• Pharmacokinetic modeling shows two doses 72 hours apart maintain urinary concentrations above the critical threshold for 161 hours (66% efficacy time over 7 days). 7