Fosfomycin Coverage for Enterococcus faecalis
Yes, fosfomycin is FDA-approved and effective for treating urinary tract infections caused by Enterococcus faecalis, but its use should be limited to uncomplicated cystitis in women only. 1
FDA-Approved Indication
- Fosfomycin tromethamine is specifically FDA-approved for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Enterococcus faecalis and Escherichia coli. 1
- The standard dosing is a single 3-gram oral dose, which provides therapeutic urinary concentrations for 24-48 hours. 2
In Vitro Activity and Clinical Efficacy
- Fosfomycin demonstrates in vitro activity against Enterococcus faecalis, with MIC50/90 values of 32/64 μg/mL in recent susceptibility testing. 3
- Clinical susceptibility rates for E. faecalis are excellent, with 94.4% of isolates susceptible to fosfomycin in US surveillance data. 4
- Bacteriological eradication rates of 75-90% are achieved 5-11 days after therapy in patients with acute uncomplicated lower UTIs. 5
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
- If bacteriuria persists or reappears after fosfomycin treatment, alternative therapeutic agents should be selected. 1
- For serious enterococcal infections (bacteremia, endocarditis, intra-abdominal infections), fosfomycin should not be used; daptomycin-based regimens are preferred. 6
Special Populations Requiring Caution
- Patients with hypernatremia, cardiac insufficiency, or renal insufficiency should use fosfomycin with caution, as the elimination half-life increases dramatically in renal impairment (from 5.7 hours to 40-50 hours in anuric patients). 2, 1
- Fosfomycin is safe in pregnancy and recommended by European Urology guidelines for asymptomatic bacteriuria in pregnant women. 2
Vancomycin-Resistant Enterococcus (VRE) Coverage
- Fosfomycin has in vitro activity against VRE and is recommended for uncomplicated UTIs caused by vancomycin-resistant E. faecalis using the same single 3-gram oral dose. 6, 2
- Limited retrospective observational studies show promising results in treating uncomplicated UTIs due to VRE. 6
- For serious VRE infections beyond uncomplicated cystitis, tigecycline is recommended for intra-abdominal infections, while daptomycin-based combinations are preferred for bacteremia and endocarditis. 6
Pharmacodynamic Considerations
- E. faecalis requires greater fosfomycin exposure for bacterial kill compared to E. faecium, with an ƒAUC0-72/MIC of 672 and ƒ%T > MIC0-72 of 70% needed for 3 log10 kill. 3
- The pharmacodynamic target for stasis in E. faecalis is an fAUC/MIC of 283, which is achievable with standard dosing. 7
- Fosfomycin heteroresistance is uncommon in Enterococcus species, unlike in Klebsiella and Pseudomonas. 7
Clinical Pitfalls to Avoid
- Do not use fosfomycin for upper urinary tract infections or complicated UTIs—fluoroquinolones or β-lactams are preferred for these indications. 2
- Do not use fosfomycin for enterococcal bacteremia, as tigecycline achieves low serum levels and fosfomycin lacks sufficient data for systemic infections. 6
- Avoid co-administration with metoclopramide, which lowers serum concentrations and urinary excretion of fosfomycin. 1