When More Than One Dose of Fosfomycin is Indicated
More than one dose of fosfomycin is indicated ONLY for prophylaxis of recurrent UTIs (≥3 UTIs/year or 2 UTIs in 6 months), dosed at 3 grams every 10 days for 6-12 months—never for acute treatment of a single UTI episode. 1
Standard Treatment: Single Dose Only
For acute uncomplicated cystitis in women, fosfomycin is administered as a single 3-gram dose with no repetition. 2, 1
The FDA label explicitly states: "Do not use more than one single dose of fosfomycin tromethamine to treat a single episode of acute cystitis. Repeated daily doses did not improve clinical success or microbiological eradication rates compared to single-dose therapy, but did increase the incidence of adverse events." 3
Clinical cure rates with single-dose fosfomycin range from 89-91%, with microbiological cure rates of 78-83%. 1
This single-dose regimen provides therapeutic urinary concentrations for 24-48 hours. 4
The ONLY Exception: Prophylactic Dosing for Recurrent UTIs
Fosfomycin may be repeated exclusively for prophylaxis (not acute treatment) in women with recurrent UTIs. 1
Prophylactic regimen: 3 grams every 10 days for 6-12 months with periodic reassessment. 1
Qualifying criteria for prophylaxis: ≥3 UTIs per year OR 2 UTIs within 6 months. 1
This is the only scenario where multiple doses are appropriate—it is not for treating an active infection but for preventing future episodes. 1
When Treatment Fails: Switch, Don't Repeat
If symptoms do not resolve within 2-3 days after fosfomycin, the correct approach is to obtain a urine culture and switch to a different antibiotic class—not to repeat fosfomycin. 1
For treatment failure or symptom recurrence within 2 weeks: Perform urine culture with susceptibility testing and retreat with a 7-day regimen using a different agent (not fosfomycin). 1
Alternative agents for treatment failure include: nitrofurantoin (5 days), trimethoprim-sulfamethoxazole (3 days), or fluoroquinolones (3 days). 2, 1
Critical Pitfalls to Avoid
Do not use multiple doses of fosfomycin for acute treatment of complicated UTIs, pyelonephritis, or in men. 1, 4
Male UTIs are inherently complicated and require 7-day treatment with agents like trimethoprim-sulfamethoxazole or fluoroquinolones—never single-dose fosfomycin. 1
Fosfomycin should not be used for pyelonephritis or complicated UTIs due to insufficient efficacy data. 4
Avoid fosfomycin if early pyelonephritis is suspected, as it has lower efficacy for upper tract infections. 2
Off-Label Multiple-Dose Use: Limited Evidence
While some retrospective studies describe off-label use of multiple-dose fosfomycin (typically 3 grams every 48-72 hours for 3 doses) for complicated UTIs with multidrug-resistant organisms, this is not guideline-recommended. 5, 6
One retrospective study showed clinical resolution in 67.3% of complicated UTI episodes treated with multiple-dose fosfomycin (mean 6.1 days), but bacteriologic resolution occurred in only 48.7%. 5
This off-label approach should be reserved for patients who have failed other agents, are infected with MDR pathogens, or cannot tolerate first-line treatments—and only after consultation with infectious disease specialists. 7
The FDA-approved indication remains single-dose only for uncomplicated cystitis. 3