What is the recommended treatment for uncomplicated urinary tract infections (uUTIs) using Fosfomycin (Fosfomycin)?

Fosfomycin Treatment for Uncomplicated Urinary Tract Infections

For uncomplicated urinary tract infections (UTIs) in women, a single 3-gram oral dose of fosfomycin tromethamine is the recommended treatment regimen. 1, 2

Indications and FDA Approval

• Fosfomycin is FDA-approved specifically for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis 2
• It is recommended as one of three first-line therapies for uncomplicated UTIs by the American Urological Association with a strong recommendation (Grade B evidence) 1
• Fosfomycin is NOT indicated for pyelonephritis, complicated UTIs, perinephric abscess, or routine use in men due to limited efficacy data 1, 2

Dosing and Administration

• The recommended dosage is one sachet (3 grams) of fosfomycin tromethamine granules for oral solution 2
• This single-dose regimen provides therapeutic urinary concentrations for 24-48 hours 1
• Fosfomycin may be taken with or without food but must always be mixed with water before ingestion 2

Clinical Efficacy

• Clinical efficacy is comparable to other first-line agents, with high clinical recovery rates and bacteriological eradication rates 1
• In clinical studies, fosfomycin demonstrated a clinical success rate of 74.8% at 48 hours for UTIs, with even higher success rates (89.9%) for NHSN-defined UTIs 3
• While bacterial efficacy may be somewhat lower than some other first-line agents, the convenience of single-dose administration and minimal collateral damage to intestinal flora make fosfomycin a valuable option 1

Antimicrobial Coverage

• Fosfomycin maintains excellent activity against E. coli (95.9-99.6% susceptibility), including ESBL-producing strains (96.1% susceptibility) 4, 5
• It also demonstrates good activity against Enterococcus faecalis (94.4% susceptibility), comparable to nitrofurantoin (98.1%) 4
• For vancomycin-resistant Enterococcus (VRE) causing uncomplicated UTIs, the same single 3-gram oral dose is recommended 1

Comparison with Other First-Line Agents

• Fosfomycin has similar clinical efficacy to nitrofurantoin but with the advantage of single-dose administration versus multiple-day regimens 1, 6
• In a meta-analysis comparing fosfomycin to nitrofurantoin, no significant differences were found in clinical cure rates (RR 0.95% CI - 0.81,1.12) or microbiological cure rates (RR 0.96,95% CI - 0.84,1.08) 6
• Fosfomycin often remains effective against isolates resistant to other first-line UTI treatments, making it valuable for multidrug-resistant infections 5

Follow-up and Monitoring

• Routine post-treatment urinalysis or urine cultures are not indicated for asymptomatic patients 1
• If symptoms do not resolve by the end of treatment or recur within 2 weeks, urine culture and antimicrobial susceptibility testing should be performed 1
• If bacteriuria persists or reappears after treatment with fosfomycin, other therapeutic agents should be selected 2

Adverse Effects

• The most common adverse events include diarrhea, nausea, and vomiting 1
• Adverse events are generally mild and occur in approximately 2% of patients 3

Special Populations

• For pregnant women with asymptomatic bacteriuria, fosfomycin can be used as a single-dose treatment 1
• Fosfomycin is not recommended for asymptomatic bacteriuria except in pregnant women and before urological procedures breaching the mucosa 1

Clinical Pitfalls and Caveats

• Do not use fosfomycin for pyelonephritis or complicated UTIs as it is not FDA-approved for these indications and lacks sufficient efficacy data 1, 2
• Always mix fosfomycin granules with water before ingestion; never administer in dry form 2
• While emerging data suggests potential efficacy for complicated or multidrug-resistant UTIs (96.4% clinical success in one retrospective study), this remains off-label use 7
• Recurrent infections may occur in approximately 4.3% of cases 3