What is the recommended dosing of fosfomycin for an adult with uncomplicated cystitis?

Fosfomycin Dosing for Uncomplicated Cystitis in Adults

For an adult with uncomplicated cystitis, administer a single 3-gram oral dose of fosfomycin tromethamine mixed with water, taken with or without food. 1

Standard Dosing Regimen

• The FDA-approved dose is one sachet (3 grams) of fosfomycin tromethamine granules dissolved in water as a single oral dose for women 18 years and older with acute uncomplicated cystitis. 1
• This single dose provides therapeutic urinary concentrations (>128 mg/L) for 24-48 hours, which is sufficient to inhibit most urinary pathogens. 2, 3
• The medication must be mixed with water before ingestion and should never be taken in dry form. 1

Clinical Efficacy

• Clinical cure rates reach approximately 91% at 5-9 days post-treatment, with microbiological eradication in 78-83% of cases. 2
• While bacteriological efficacy is slightly lower than 3-day courses of trimethoprim-sulfamethoxazole or fluoroquinolones, overall clinical outcomes are comparable with the advantage of single-dose convenience and minimal disruption to intestinal flora. 2

Position in Treatment Algorithm

• First-line option when: Local E. coli resistance to trimethoprim-sulfamethoxazole exceeds 20%, or when nitrofurantoin is contraindicated (e.g., eGFR <30 mL/min/1.73 m²). 2
• Preferred alternatives: Nitrofurantoin 100 mg twice daily for 5 days (93% clinical efficacy) or trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 days when local resistance is <20%. 2
• Reserve fluoroquinolones (ciprofloxacin 250 mg twice daily for 3 days) only for culture-proven resistant pathogens or when all first-line agents are contraindicated. 2

Critical Limitations and Common Pitfalls

• Do NOT use fosfomycin for pyelonephritis or upper urinary tract infections – insufficient efficacy data exists for these conditions; use fluoroquinolones or ceftriaxone instead. 4, 2, 5
• Do NOT use for complicated UTIs – fosfomycin is approved only for uncomplicated lower UTI (cystitis) in women. 5, 6
• Do NOT use in men – clinical efficacy data is limited in male patients with UTI. 2
• The WHO Expert Committee specifically excluded fosfomycin from their essential medicines list for lower UTI treatment because randomized trials showed nitrofurantoin (5 days) achieved significantly greater clinical and microbiologic resolution at 28 days compared to single-dose fosfomycin, and fosfomycin is more expensive. 4

When to Obtain Urine Culture

• Do NOT routinely culture asymptomatic patients after treatment. 2
• Obtain culture and susceptibility testing if:
  • Symptoms persist at the end of treatment
  • Symptoms recur within 2 weeks after completion
  • Fever, flank pain, or systemic signs develop (suggesting pyelonephritis)
  • Atypical presentation or risk factors for resistant organisms exist 2

Special Populations

• Pregnancy: Fosfomycin is pregnancy category B and is recommended for asymptomatic bacteriuria in pregnant women as standard short-course or single-dose treatment. 2
• Renal impairment: Standard dosing can be used when eGFR ≥30 mL/min/1.73 m²; monitor electrolytes as fosfomycin can cause hypokalemia, hypocalcemia, hypomagnesemia, and hypernatremia. 2
• Cardiac or renal insufficiency: Use with caution due to sodium content and electrolyte disturbances. 2

Resistance Considerations

• Fosfomycin maintains low resistance rates: only 2.6% prevalence in initial E. coli infections, with persistent resistance of only 5.7% at 9 months. 2
• It remains effective against multidrug-resistant pathogens including ESBL-producing organisms, vancomycin-resistant Enterococcus (VRE), and MRSA causing uncomplicated cystitis. 2
• Overall susceptibility to fosfomycin is 94.4% across contemporary urine isolates. 7

Adverse Effects

• Common adverse events (diarrhea, nausea, headache) occur in 5.6-28% of patients but are generally mild and self-limited. 2
• No serious drug-related adverse events have been reported in clinical trials. 2