What is the recommended fosfomycin tromethamine dosing for an adult with uncomplicated urinary tract infection, and how should the regimen be modified for recurrent infection, multidrug‑resistant organisms, complicated cystitis, severe renal impairment, and pregnancy?

Fosfomycin Dosing for Uncomplicated Urinary Tract Infection

For uncomplicated cystitis in adult women, administer fosfomycin tromethamine 3 grams as a single oral dose, mixed with water. 1, 2, 3

Standard Dosing Regimen

• Single 3-gram oral dose is the FDA-approved and guideline-recommended regimen for uncomplicated cystitis in women aged 18 years and older. 1, 3
• Mix the granules with water before ingesting; never take in dry form. 3
• May be taken with or without food, though absorption is reduced under fed conditions (bioavailability drops from 37% fasting to 30% fed). 3
• Therapeutic urinary concentrations (>100 mcg/mL) are maintained for 24–48 hours after a single dose, sufficient to eradicate most uropathogens. 1, 3, 4
• Clinical cure rates of approximately 91% and microbiological eradication rates of 78–83% are achieved 5–9 days post-treatment. 1, 5

Position in Treatment Algorithm

• Fosfomycin is recommended as a first-line option by the European Association of Urology, American Urological Association, and Infectious Diseases Society of America for uncomplicated cystitis in women. 1, 2
• Particularly appropriate when local trimethoprim-sulfamethoxazole (TMP-SMX) resistance exceeds 20% or when the patient has received TMP-SMX within the prior 3 months. 1
• Resistance rates remain low: 2.6% in initial E. coli infections and 5.7% at 9 months. 1

Modifications for Special Populations

Recurrent Uncomplicated UTI

• The same single 3-gram dose is appropriate for each separate episode of uncomplicated cystitis. 1
• Multiple guidelines endorse fosfomycin for subsequent UTI episodes, implying it can be used repeatedly for distinct infections. 1
• An off-label multi-dose regimen (3 grams on days 1,3, and 5) has been suggested by European Urology guidelines for gonococcal urethritis, but this is not standard for recurrent cystitis. 1

Multidrug-Resistant Organisms

• Fosfomycin retains excellent activity against ESBL-producing E. coli, vancomycin-resistant Enterococcus (VRE), and MRSA causing uncomplicated cystitis. 1, 2
• The same single 3-gram dose is recommended for VRE-associated uncomplicated UTI. 1
• Minimal cross-resistance with other antibiotic classes makes fosfomycin particularly valuable when resistance is documented. 1, 4

Renal Impairment

• No dose adjustment is required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). 1
• For severe renal impairment (eGFR <30 mL/min/1.73 m²) or anuric patients, elimination half-life increases dramatically from 5.7 hours to 40–50 hours. 1, 3
• Use with caution in patients with severe renal dysfunction; monitor electrolytes (fosfomycin can cause hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia). 1
• In anuric patients undergoing hemodialysis, the half-life extends to 40 hours. 3

Pregnancy

• Fosfomycin is safe in pregnancy and recommended by European Urology guidelines for asymptomatic bacteriuria in pregnant women as either standard short-course or single-dose treatment. 1, 2
• The single 3-gram dose provides similar bacteriological efficacy to 5–7 day courses of cefuroxime or amoxicillin-clavulanate in pregnant women. 5
• FDA pregnancy category rating is favorable, though the label states it should be used "only if clearly needed." 2

Critical Contraindications and Limitations

• Do NOT use fosfomycin for pyelonephritis or upper urinary tract infections—insufficient tissue penetration and lack of efficacy data. 1, 2
• Do NOT use in men with UTIs—limited efficacy data in this population. 1, 2
• Do NOT use for complicated UTIs—fosfomycin is restricted to uncomplicated cystitis only. 1, 2
• Avoid in patients with hypernatremia, cardiac insufficiency, or severe renal insufficiency (especially when considering IV formulation for carbapenem-resistant organisms). 1

When Treatment Fails

• If symptoms persist after 2–3 days or recur within 2 weeks, obtain urine culture and susceptibility testing immediately. 1
• Switch to a different antibiotic class for a 7-day course (not the original short regimen): consider nitrofurantoin 100 mg twice daily for 5 days, TMP-SMX 160/800 mg twice daily for 3 days (if susceptible), or a fluoroquinolone for 3 days (culture-guided only). 1
• Assume the original pathogen is resistant to fosfomycin when retreating. 1

Comparative Efficacy

• Fosfomycin shows slightly lower bacteriological efficacy compared to 3-day TMP-SMX or fluoroquinolones (based on FDA submission data), but overall clinical outcomes are comparable. 1, 5
• Single-dose convenience and minimal disruption to intestinal flora (reducing C. difficile risk) make fosfomycin advantageous over multi-day regimens. 1, 2
• Clinical cure rates are similar to nitrofurantoin (93%), TMP-SMX (93%), and fluoroquinolones (90%), though microbiological eradication is modestly lower. 1, 6

Common Adverse Effects

• Diarrhea, nausea, and vomiting are most commonly reported, occurring in 5.6–28% of patients. 1, 4
• Gastrointestinal symptoms are typically transient, mild, and self-limiting. 4, 7
• Headache may occur but is generally well tolerated. 1

Key Clinical Pitfalls to Avoid

• Never use oral fosfomycin for suspected pyelonephritis—switch to fluoroquinolones or parenteral cephalosporins if fever, flank pain, or costovertebral angle tenderness is present. 1
• Do not prescribe multiple doses for uncomplicated cystitis—the single 3-gram dose is the evidence-based regimen. 1, 3
• Do not use in complicated UTIs (catheter-associated, obstruction, immunosuppression)—efficacy is unproven. 1
• Avoid metoclopramide co-administration—it lowers serum concentrations and urinary excretion of fosfomycin. 3