Is fosfomycin (generic name) appropriate for treating an uncomplicated urinary tract infection (UTI) caused by gram-negative lactose fermenting organisms, such as Escherichia coli (E. coli), in an adult patient without a known history of allergy to the medication?

Fosfomycin for Gram-Negative Lactose Fermenting UTI

Yes, fosfomycin is highly appropriate for uncomplicated UTI caused by gram-negative lactose fermenting organisms, particularly E. coli, with FDA approval specifically for this indication and guideline endorsement as first-line therapy. 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 (the prototypical gram-negative lactose fermenter) and Enterococcus faecalis 1
• The standard regimen is a single 3-gram oral dose, which provides therapeutic urinary concentrations for 24-48 hours 2

Guideline Recommendations

• The American Urological Association, European Association of Urology, and American College of Physicians all recommend fosfomycin as first-line therapy for uncomplicated cystitis in women with strong evidence (Grade B) 2
• Fosfomycin is particularly recommended when trimethoprim-sulfamethoxazole resistance exceeds 20-30% in the community, making it an excellent choice in the current era of antimicrobial resistance 2

Clinical Efficacy Against E. coli

• Fosfomycin demonstrates excellent activity against E. coli, with clinical success rates of 74.8% at 48 hours and 89.9% for NHSN-defined UTIs 3
• Resistance rates remain remarkably low at only 2.6% prevalence in initial E. coli infections, with persistent resistance of only 5.7% at 9 months 2
• All 100 randomly selected ESBL-producing E. coli isolates tested at one tertiary care center were susceptible to fosfomycin, demonstrating maintained activity even against multidrug-resistant strains 3
• Fosfomycin susceptibility rates for ESBL- and AmpC β-lactamase-producing E. coli reach 96%, making it the most reliable oral option after carbapenems (100%) 4

Mechanism and Advantages

• Fosfomycin achieves mean urinary concentrations of 706 mcg/mL within 2-4 hours after a single 3-gram dose, with concentrations ≥100 mcg/mL maintained for 26 hours 1
• The single-dose regimen improves adherence compared to 3-7 day courses and causes minimal collateral damage to intestinal flora, reducing risk of C. difficile infection 2
• There is generally no cross-resistance between fosfomycin and other antibiotic classes such as beta-lactams and aminoglycosides 1

Important Limitations and Contraindications

• Fosfomycin is NOT indicated for pyelonephritis, complicated UTIs, perinephric abscess, or routine use in men due to insufficient efficacy data 2, 1
• Use with caution in patients with hypernatremia, cardiac insufficiency, or renal insufficiency, as the elimination half-life increases from 5.7 hours to 40-50 hours in anuric patients 2
• If persistence or reappearance of bacteriuria occurs after fosfomycin treatment, other therapeutic agents should be selected 1

Special Considerations for Other Lactose Fermenters

• While E. coli shows excellent susceptibility, Klebsiella species (another lactose fermenter) demonstrate significantly higher resistance rates of 19% compared to 1% for E. coli 5
• Klebsiella infections are more likely to fail fosfomycin treatment and more likely to be reported as fosfomycin resistant in cases of relapse 5
• The cumulative fraction of bacterial response is 99% against E. coli but only 55% against Klebsiella species 6

Clinical Pitfalls to Avoid

• Do not use fosfomycin for upper urinary tract infections—fluoroquinolones or β-lactams are preferred for pyelonephritis 2
• Avoid co-administration with metoclopramide, which lowers serum concentrations and urinary excretion of fosfomycin 1
• Do not assume all gram-negative lactose fermenters respond equally—verify the specific organism is E. coli rather than Klebsiella when possible 5, 6