What is the appropriate fosfomycin (phosphomycin) dosing for an adult woman with uncomplicated cystitis, including oral single‑dose regimen, intravenous dosing for complicated infections, adjustments for impaired renal function, and alternative oral agents?

Fosfomycin Dosing for Uncomplicated Cystitis in Adult Women

Standard Oral Single-Dose Regimen

For acute uncomplicated cystitis in adult women, administer fosfomycin trometamol 3 grams as a single oral dose. 1, 2

• This single-dose regimen provides therapeutic urinary concentrations for 24-48 hours, sufficient to eradicate most uropathogens. 2
• The clinical efficacy rate is approximately 91% at 5-9 days post-treatment, with microbiological cure rates of 78-83%. 1, 2
• Fosfomycin demonstrates somewhat inferior bacteriological efficacy compared to 3-day trimethoprim-sulfamethoxazole or fluoroquinolones, but clinical outcomes remain comparable with the advantage of single-dose convenience and minimal collateral damage to intestinal flora. 1, 2

Position in Treatment Algorithm

Fosfomycin is recommended as a first-line agent for uncomplicated cystitis when:

• Trimethoprim-sulfamethoxazole resistance exceeds 20% in your community. 1, 2
• The patient has used trimethoprim-sulfamethoxazole within the previous 3 months. 2
• Single-dose convenience is prioritized to improve adherence. 2
• Treatment of multidrug-resistant organisms (ESBL-producing E. coli, VRE, MRSA) is needed. 2

Avoid fosfomycin for:

• Suspected pyelonephritis or upper urinary tract infections—insufficient efficacy data exists for these conditions. 2
• Early pyelonephritis concerns—use nitrofurantoin, trimethoprim-sulfamethoxazole, or fluoroquinolones instead. 1

Intravenous Dosing for Complicated Infections

Oral fosfomycin is NOT recommended for complicated urinary tract infections or pyelonephritis. 2

• For complicated infections requiring fosfomycin, intravenous formulation may be considered, though specific IV dosing is not detailed in current U.S. guidelines. 2
• The IV formulation has an elimination half-life of 5.7 hours in patients with normal renal function, increasing to 40-50 hours in anuric patients. 2

Renal Function Adjustments

No dose adjustment is required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). 2

• For CKD stage 3b (eGFR 30-44 mL/min/1.73 m²), use standard 3-gram single dose without modification. 2
• Use with caution in severe renal impairment, hypernatremia, cardiac insufficiency, or anuric patients due to prolonged elimination and electrolyte disturbances. 2
• Monitor electrolytes (potassium, calcium, magnesium, sodium) during and after treatment, particularly in patients with pre-existing renal dysfunction. 2

Alternative Oral Agents for Uncomplicated Cystitis

When fosfomycin cannot be used, select from these alternatives based on local resistance patterns and patient factors:

First-Line Alternatives

Nitrofurantoin monohydrate/macrocrystals 100 mg twice daily for 5-7 days:

• Clinical efficacy 93%, microbiological efficacy 88%. 1, 2
• Avoid if eGFR <30 mL/min/1.73 m² or if pyelonephritis is suspected. 2

Trimethoprim-sulfamethoxazole 160/800 mg (one double-strength tablet) twice daily for 3 days:

• Clinical efficacy 93%, microbiological efficacy 94%. 1, 2
• Only use if local E. coli resistance is <20% AND the patient has not used this agent in the previous 3 months. 1, 2

Second-Line Alternatives

Fluoroquinolones (3-day regimen):

• Ciprofloxacin 250 mg twice daily or levofloxacin 250 mg once daily for 3 days. 1
• Clinical efficacy 90%, microbiological efficacy 91%. 1
• Reserve for documented resistant pathogens or when first-line agents cannot be used due to high propensity for collateral damage and promotion of resistance. 1, 2

β-Lactams (3-7 day regimen):

• Amoxicillin-clavulanate, cefdinir, cefaclor, or cefpodoxime-proxetil. 1
• Clinical efficacy 89%, microbiological efficacy 82%. 1
• Use only when other recommended agents cannot be used due to inferior efficacy and higher adverse effect rates. 1
• Do NOT use amoxicillin or ampicillin alone due to poor efficacy and high resistance rates. 1

Special Populations

Pregnancy:

• Fosfomycin 3 grams single dose is safe and recommended for uncomplicated cystitis and asymptomatic bacteriuria in pregnant women, including first trimester. 2, 3
• Alternative: Nitrofurantoin 50-100 mg four times daily for 7 days (avoid in third trimester near delivery). 3
• Cephalosporins (cephalexin 500 mg four times daily for 7-14 days) are appropriate alternatives throughout pregnancy. 3

Postpartum/Lactating Women:

• Single 3-gram dose allows continuation of breastfeeding without prolonged antibiotic exposure. 4

Treatment Failure Management

If symptoms persist at end of treatment or recur within 2 weeks:

• Obtain urine culture with antimicrobial susceptibility testing. 2
• Assume the pathogen is resistant to the initial agent. 2
• Prescribe a different antibiotic for 7 days: nitrofurantoin for 5-7 days, trimethoprim-sulfamethoxazole for 3 days, or a fluoroquinolone for 3 days. 2

Common Pitfalls to Avoid

• Do not use fosfomycin for pyelonephritis—urinary concentrations are adequate, but systemic/tissue penetration data for upper tract infections is insufficient. 2
• Do not obtain routine post-treatment urine cultures in asymptomatic patients—this promotes unnecessary antibiotic use and resistance. 2
• Do not use multiple doses of fosfomycin for uncomplicated cystitis—the standard single 3-gram dose is the evidence-based regimen. 1, 2
• Do not prescribe fosfomycin for men with UTIs—clinical efficacy data is limited in this population. 2

Common Adverse Effects

• Diarrhea, nausea, headache (reported in 5.6-28% of patients). 1, 2, 5
• Generally well-tolerated with no serious drug-related adverse events in clinical trials. 5