What is the recommended treatment and dosage of fosfomycin for urinary tract infections?

Fosfomycin Treatment for Urinary Tract Infections

Fosfomycin tromethamine is recommended as a single 3g oral dose for uncomplicated urinary tract infections in women, with clinical efficacy rates of approximately 91% and microbiological efficacy rates of 80%. 1

Indications and Dosing

Uncomplicated UTIs

• Standard dosing: One 3g sachet of fosfomycin tromethamine as a single dose 2
• Must be mixed with water before ingestion (not taken in dry form) 2
• Can be taken with or without food 2
• Achieves high urinary concentrations for 24-48 hours after a single dose 3

Special Populations

• VRE UTIs: A single dose of fosfomycin 3g PO is recommended for uncomplicated urinary tract infections due to vancomycin-resistant enterococci (VRE) 1
• Not recommended for males: The European Association of Urology recommends against using fosfomycin as first-line treatment for UTIs in males due to limited evidence 4
• Pregnancy: Fosfomycin has a favorable pregnancy category rating and has shown similar bacteriological efficacy to a 5-day course of cefuroxime axetil or a 7-day course of amoxicillin/clavulanic acid in pregnant women with asymptomatic bacteriuria 5

Efficacy and Positioning in Treatment Guidelines

Efficacy Data

• Clinical efficacy rate: 91% 1
• Microbiological efficacy rate: 80% (78-83%) 1
• Bacteriological eradication rates of 75-90% at 5-11 days post-therapy 3

Guideline Recommendations

• Fosfomycin is recommended as a first-line agent by the European Association of Urology 1
• The World Health Organization recommends fosfomycin as one of the first-line treatment options for uncomplicated UTIs caused by E. coli, along with nitrofurantoin and trimethoprim-sulfamethoxazole 4
• Fosfomycin is particularly valuable due to:
  • Convenience of single-dose regimen 1
  • In vitro activity against resistant gram-negative rods 1
  • Minimal propensity for collateral damage to gut flora 1

Antimicrobial Activity

• Particularly active against Escherichia coli (including ESBL-producing strains) 5
• Active against Proteus mirabilis, Klebsiella pneumoniae, and Staphylococcus saprophyticus 5
• Shows activity against multidrug-resistant pathogens including VRE, MRSA, and ESBL-producing gram-negative rods 1
• Susceptibility of uropathogens to fosfomycin has remained relatively stable over time 5

Alternative Dosing Regimens for Complicated UTIs

• While not FDA-approved, some studies have evaluated multiple-dose regimens for complicated UTIs:
  • Three doses of 3g fosfomycin tromethamine (days 1,3, and 5) have shown efficacy for complicated lower UTIs with clinical efficacy rates of 62.69% and microbiological efficacy rates of 83.87% 6
  • For complicated or MDR UTIs, limited retrospective data suggests potential efficacy with success rates of 96.4% clinically and 75% microbiologically 7

Safety and Tolerability

• Generally well tolerated 3, 5
• Most common adverse events are gastrointestinal symptoms:
  • Diarrhea
  • Nausea
  • Headache 1
• Adverse event rate is approximately 5.6% 6

Important Considerations

• Susceptibility testing for fosfomycin is not routinely performed in many clinical laboratories 1
• The bacterial efficacy of fosfomycin is lower than some other first-line agents, but clinical efficacy is comparable 1
• The effect on intestinal flora after a single 3g dose is probably minor 1
• Fosfomycin may become increasingly useful as resistance among uropathogens increases, particularly when no other oral agents with in vitro activity are available 1

Caveats

• Despite in vitro activity against multidrug-resistant pathogens, specific recommendations for the role of fosfomycin in treating MDR uropathogens are limited by lack of randomized controlled trial data 1
• Observational studies support clinical efficacy against resistant organisms 1, 7
• The FDA-approved indication is specifically for uncomplicated UTIs in women 2