Does fosfomycin offer coverage for Escherichia coli (E. coli) urinary tract infections (UTIs)?

Fosfomycin Coverage for E. coli UTI

Yes, fosfomycin provides excellent coverage for Escherichia coli urinary tract infections and is FDA-approved and guideline-recommended specifically for this indication in uncomplicated cystitis. 1

FDA-Approved Indication

• Fosfomycin tromethamine is FDA-approved specifically for uncomplicated urinary tract infections (acute cystitis) in women caused by susceptible strains of Escherichia coli and Enterococcus faecalis 1
• The drug achieves mean urinary concentrations of 706 mcg/mL within 2-4 hours after a single 3-gram oral dose, maintaining concentrations ≥100 mcg/mL for 26 hours—well above the levels needed to inhibit most E. coli strains 1

Microbiological Activity Against E. coli

• Fosfomycin demonstrates bactericidal activity against E. coli in urine at therapeutic doses through irreversible inhibition of bacterial cell wall synthesis 1
• The drug shows in vitro activity against most E. coli strains, with bacteriological eradication rates of 75-90% at 5-11 days post-therapy and 62-93% at 4-6 weeks 2
• Importantly, there is generally no cross-resistance between fosfomycin and other antibiotic classes (beta-lactams, aminoglycosides, fluoroquinolones), making it valuable when E. coli resistance to traditional agents is high 1, 2

Guideline Recommendations

• The American Urological Association recommends fosfomycin as one of three first-line therapies for uncomplicated UTIs with strong recommendation (Grade B evidence) 3
• The European Association of Urology lists fosfomycin trometamol as a first-line treatment option for uncomplicated cystitis in women, with clinical efficacy comparable to nitrofurantoin but with single-dose convenience 3
• Guidelines suggest fosfomycin becomes cost-effective when trimethoprim resistance in E. coli exceeds 30-35% 4

Multidrug-Resistant E. coli

• Fosfomycin demonstrates particularly strong activity against multidrug-resistant (MDR) E. coli, including ESBL-producing strains 3, 5
• In female adolescents with MDR E. coli UTIs, single-dose fosfomycin achieved 97% clinical cure and 94% microbiological cure rates 6
• Clinical success rates >78% have been documented for community-acquired ESBL-producing E. coli lower UTIs 5

Critical Limitations

• Fosfomycin is NOT indicated for pyelonephritis or complicated UTIs—it should only be used for uncomplicated cystitis 1, 3
• The European Association of Urology explicitly does not recommend fosfomycin for routine use in men with UTIs due to limited clinical efficacy data in this population 7
• While bacterial efficacy is somewhat lower than some other first-line agents, clinical efficacy remains comparable, with the single-dose regimen offering significant adherence advantages 3

Emerging Resistance Concerns

• Plasmid-mediated fosfomycin resistance (particularly fosA genes) is emerging in E. coli isolates worldwide, with resistant strains exhibiting MICs of 64 to >256 mg/L 8
• Close surveillance and monitoring of fosfomycin resistance patterns is essential to maintain its utility as a treatment option 8
• If bacteriuria persists or reappears after fosfomycin treatment, alternative therapeutic agents should be selected 1

Practical Advantages

• Single 3-gram oral dose improves adherence compared to 3-7 day regimens 3
• Minimal collateral damage to intestinal flora compared to other antibiotics 3
• Safe in pregnancy for asymptomatic bacteriuria 3
• Can be taken without regard to food, though peak urinary concentrations occur slightly later with high-fat meals 1