What is the recommended dosing of fosfomycin (Fosfomycin) for uncomplicated urinary tract infections (UTIs)?

Fosfomycin Dosing for Uncomplicated UTI

For uncomplicated urinary tract infections in women, administer a single 3-gram oral dose of fosfomycin tromethamine, mixed with water before ingestion. 1

Standard Dosing Regimen

• The FDA-approved dose is one sachet (3 grams) of fosfomycin tromethamine as a single oral dose for women 18 years and older with uncomplicated UTI (acute cystitis). 1
• The medication may be taken with or without food, but must always be mixed with water before ingestion—never take in dry form. 1
• This single dose provides therapeutic urinary concentrations for 24-48 hours, which is sufficient to eradicate most uropathogens. 2, 3

Guideline Support and Evidence Quality

• Multiple major guidelines recommend fosfomycin as first-line therapy: the American Urological Association (Grade B evidence), European Association of Urology, and American College of Physicians all endorse the single 3-gram dose for uncomplicated cystitis in women. 2, 3
• Clinical recovery rates of 88.9% and bacteriological eradication rates of 94.9% have been demonstrated with this single-dose regimen. 4
• The Infectious Diseases Society of America classifies fosfomycin with an A-I evidence rating, though notes slightly inferior bacteriological efficacy compared to 3-day trimethoprim-sulfamethoxazole or fluoroquinolones—however, clinical efficacy remains comparable. 2, 3

Special Clinical Situations

VRE-Caused UTI

• For uncomplicated UTI due to vancomycin-resistant Enterococcus (VRE), use the same single 3-gram oral dose. 5, 2

Multidrug-Resistant Organisms

• Fosfomycin is highly effective against ESBL-producing E. coli, VRE, and MRSA causing uncomplicated cystitis, with only 2.6% resistance prevalence in initial E. coli infections. 2
• Consider fosfomycin as first-line when trimethoprim-sulfamethoxazole resistance exceeds 20-30% in your community. 2

Pregnant Women

• Fosfomycin is safe in pregnancy and recommended for asymptomatic bacteriuria in pregnant women as either standard short-course or single-dose treatment. 2, 3
• Single-dose fosfomycin had similar bacteriological efficacy to 5-7 day courses of cefuroxime or amoxicillin/clavulanic acid in pregnant women. 6

Critical Contraindications and Limitations

Do NOT Use Fosfomycin For:

• Pyelonephritis or upper UTIs (insufficient efficacy data; use fluoroquinolones or β-lactams instead). 2, 3
• Complicated UTIs (consider IV formulation if fosfomycin is necessary). 2
• Men with UTIs (limited efficacy data in this population). 2, 3
• Patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency (elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients). 2

Key Advantages

• Single-dose administration eliminates compliance issues associated with 3-7 day regimens, improving adherence. 2, 3
• Minimal disruption to intestinal flora compared to fluoroquinolones and cephalosporins, reducing risk of C. difficile infection. 2, 3
• Low resistance rates that have remained stable over time. 2

Common Adverse Effects

• Gastrointestinal side effects (diarrhea, nausea, vomiting) occur in approximately 4-25% of patients but are typically mild, transient, and self-limiting. 2, 4, 7
• One study reported 43% of patients experiencing side effects at day 4, though most were mild gastrointestinal complaints. 7

Follow-Up Considerations

• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients. 2
• If symptoms do not resolve by end of treatment or recur within 2 weeks, perform urine culture and antimicrobial susceptibility testing. 2