What is the recommended treatment protocol for intravesical (directly into the bladder) fosfomycin for recurrent or complicated Urinary Tract Infections (UTIs)?

Intravesical Fosfomycin for UTI

Intravesical (bladder instillation) fosfomycin is NOT a standard or guideline-recommended treatment for urinary tract infections. The current evidence and guidelines exclusively support oral fosfomycin administration, not intravesical delivery.

Current Evidence-Based Fosfomycin Use

Oral Fosfomycin is the Standard Route

• Oral fosfomycin tromethamine 3 grams as a single dose is recommended as first-line therapy for uncomplicated cystitis in women only 1, 2
• This oral formulation achieves therapeutic urinary concentrations of 1053-4415 mg/L within 4 hours, maintaining levels >128 mg/L for 24-48 hours—sufficient to inhibit most urinary pathogens 3
• The single-dose oral regimen provides high clinical recovery rates (74.8-96.4%) with minimal adverse effects 2, 4, 5

Limitations of Oral Fosfomycin

• Oral fosfomycin should NOT be used for pyelonephritis, complicated UTIs, or routinely in men due to insufficient efficacy data 2
• For complicated UTIs requiring fosfomycin, intravenous formulation (not intravesical) may be more appropriate 2

Alternative Intravesical Therapies (Not Fosfomycin)

What IS Recommended for Intravesical Use

The 2024 European Association of Urology guidelines recommend endovesical instillations of hyaluronic acid or hyaluronic acid combined with chondroitin sulfate for recurrent UTI prevention when less invasive approaches have failed (weak recommendation) 1

This represents the only bladder instillation therapy with guideline support for UTI management—and it is NOT fosfomycin.

Clinical Approach for Recurrent/Complicated UTIs

Stepwise Management Algorithm

For recurrent UTIs, follow this hierarchy 1:

1. Non-antimicrobial measures first:

   • Increased fluid intake in premenopausal women (weak recommendation) 1
   • Vaginal estrogen in postmenopausal women (strong recommendation) 1
   • Immunoactive prophylaxis (strong recommendation) 1
   • Methenamine hippurate in women without urinary tract abnormalities (strong recommendation) 1

2. Intravesical therapy (if above fails):

   • Hyaluronic acid or hyaluronic acid/chondroitin sulfate instillations 1

3. Antimicrobial prophylaxis (if non-antimicrobial interventions fail):

   • Continuous or postcoital antimicrobial prophylaxis (strong recommendation) 1

For Complicated UTIs Requiring Fosfomycin

If fosfomycin is needed for complicated/MDR UTIs:

• Oral regimen: 3 grams every 48-72 hours for 3 total doses (off-label use for patients who failed other agents or have MDR pathogens) 6
• Intravenous regimen: 6 grams every 8 hours for 7 days (14 days with concurrent bacteremia) for complicated upper UTIs 6

Critical Pitfalls to Avoid

• Do not attempt intravesical fosfomycin administration—there is no evidence base, no standardized protocol, and no guideline support for this route
• Do not use oral fosfomycin for pyelonephritis or complicated UTIs as monotherapy without considering IV formulation or alternative agents 2
• Do not prescribe fosfomycin routinely in men—clinical efficacy data is limited in this population 2
• Fosfomycin maintains excellent activity against ESBL-producing E. coli and MDR organisms, making it valuable when used appropriately 4, 6