What is the coverage of Fosfomycin (Fosfomycin tromethamine) for urinary tract infections (UTIs)?

Fosfomycin Coverage for Urinary Tract Infections

Fosfomycin provides excellent coverage for uncomplicated UTIs caused by E. coli and Enterococcus faecalis, including multidrug-resistant strains, but is FDA-approved only for uncomplicated cystitis in women and should not be used for pyelonephritis or complicated UTIs. 1

FDA-Approved Indications and Pathogens

• Fosfomycin is FDA-approved specifically for uncomplicated UTIs (acute cystitis) in women caused by susceptible strains of Escherichia coli and Enterococcus faecalis. 1

• The standard dosing is a single 3-gram oral dose, which provides therapeutic urinary concentrations for 24-48 hours. 2, 1

• Fosfomycin is explicitly NOT indicated for pyelonephritis or perinephric abscess. 1

Spectrum of Activity Against Common Uropathogens

Gram-Negative Coverage

• Fosfomycin demonstrates exceptional activity against E. coli, with 99.6% susceptibility rates in recent US surveillance data, far exceeding fluoroquinolones (65.4-65.8%), trimethoprim-sulfamethoxazole (59.9%), and comparable to nitrofurantoin (90.3%). 3

• The drug maintains activity against ESBL-producing E. coli, with MIC50 and MIC90 values of 2 and 32 µg/mL respectively among 144 ESBL-producing isolates. 3

• All 100 randomly selected ESBL-producing E. coli clinical isolates tested at a tertiary care hospital showed susceptibility to fosfomycin. 4

• Fosfomycin has in vitro activity against other Enterobacteriaceae including Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Enterobacter aerogenes, Citrobacter species, and Serratia marcescens, though clinical efficacy data for these organisms is limited. 1, 5

Gram-Positive Coverage

• For Enterococcus faecalis, fosfomycin shows 94.4% susceptibility rates, comparable to nitrofurantoin (98.1%). 3

• Fosfomycin is specifically recommended for uncomplicated UTIs caused by vancomycin-resistant Enterococcus (VRE), with the same single 3-gram oral dose. 6, 2

• The drug has in vitro activity against Enterococcus faecium, including VRE strains. 1

Limited Activity

• Fosfomycin has poor activity against Pseudomonas aeruginosa with MIC50 and MIC90 values of 64 and 128 µg/mL, making it unreliable for UTIs caused by this organism. 3

Clinical Efficacy Data

• In a cohort of 119 patients with physician-diagnosed UTIs, the clinical success rate at 48 hours was 74.8%, and among 89 patients meeting NHSN surveillance definitions for UTI, 89.9% had successful outcomes. 4

• A retrospective study of 57 patients (77.2% with complicated UTIs, 63.2% with MDR UTIs) showed that among 28 clinically evaluable patients, 96.4% achieved clinical success, and 75% of those with repeat cultures had microbiological cure. 7

• Recurrent infections occurred in only 4.3% of cases, with mild adverse events observed in 2.0%. 4

Important Clinical Limitations and Contraindications

Population Restrictions

• Fosfomycin is not recommended for routine use in men with UTIs due to limited clinical efficacy data in this population. 2

• The drug should not be used for complicated UTIs or pyelonephritis; fluoroquinolones and cephalosporins are preferred for these conditions. 2

Special Populations

• For pregnant women with asymptomatic bacteriuria, fosfomycin is recommended as a safe option (pregnancy category B) with standard short-course treatment or single-dose administration. 2, 5

• Patients with hypernatremia, cardiac insufficiency, or renal insufficiency should use fosfomycin with caution, as the elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients. 2

When to Avoid Fosfomycin

• Do not use fosfomycin for asymptomatic bacteriuria except in pregnant women and before urological procedures breaching the mucosa. 2

• If bacteriuria persists or reappears after fosfomycin treatment, other therapeutic agents should be selected. 1

Guideline Recommendations

• The American Urological Association (AUA) recommends fosfomycin as one of three first-line therapies for uncomplicated UTIs with strong recommendation (Grade B evidence). 2

• The European Association of Urology lists fosfomycin as a first-line treatment option for uncomplicated cystitis in women, with comparable clinical efficacy to nitrofurantoin but with the advantage of single-dose administration. 2

• The Infectious Diseases Society of America (IDSA) recommends fosfomycin as an alternative treatment option for multi-drug resistant pathogens, including ESBL-producing gram-negative bacteria, VRE, and MRSA. 2

Advantages Over Other Agents

• Fosfomycin has minimal propensity for collateral damage to intestinal flora, resulting in minimal disruption to the gut microbiome compared to other antibiotics. 2

• The single-dose convenience improves adherence compared to 3-7 day regimens. 2

• There is generally no cross-resistance between fosfomycin and other classes of antibacterial agents such as beta-lactams and aminoglycosides. 1

Common Pitfalls to Avoid

• Do not use fosfomycin for pyelonephritis or complicated UTIs despite its activity against resistant organisms—insufficient clinical data supports efficacy in these conditions. 2, 1

• Avoid co-administration with metoclopramide, which lowers serum concentrations and urinary excretion of fosfomycin. 1

• Do not rely on fosfomycin for Pseudomonas aeruginosa UTIs due to high MIC values and unreliable activity. 3

• Most common adverse effects are gastrointestinal: diarrhea, nausea, and vomiting. 2