Is fosfomycin a good treatment choice for Enterococcus faecalis prostatitis?

Fosfomycin for Enterococcus faecalis Prostatitis

Fosfomycin is not a good first-line treatment choice for Enterococcus faecalis prostatitis, but may serve as a salvage option when other antibiotics cannot be used due to resistance or allergy. The FDA has only approved oral fosfomycin for uncomplicated urinary tract infections (acute cystitis) in women, specifically excluding pyelonephritis and perinephric abscess 1. Prostatitis represents a deep-seated, complicated infection that falls outside this approved indication.

Key Limitations

FDA Approval and Evidence Gap

• Oral fosfomycin is FDA-approved exclusively for uncomplicated UTI caused by E. faecalis, not for prostatitis 1
• The FDA label explicitly states it is "not indicated for the treatment of pyelonephritis or perinephric abscess," and prostatitis represents a similarly complex infection requiring prolonged tissue penetration 1
• No randomized controlled trials exist evaluating fosfomycin for bacterial prostatitis 2, 3
• Current evidence consists only of small cohort studies and case reports, representing low-quality data 3

Efficacy Concerns

• Fosfomycin demonstrates lower bacterial eradication rates compared to other first-line agents for urinary infections 4
• In uncomplicated cystitis, bacterial efficacy is inferior to fluoroquinolones and trimethoprim-sulfamethoxazole, though clinical efficacy may be comparable 4
• For E. faecalis specifically, in vitro bladder models show that these organisms require greater fosfomycin exposure (ƒAUC0-72/MIC of 672 and ƒ%T > MIC0-72 of 70%) compared to E. faecium to achieve bactericidal activity 5

When Fosfomycin May Be Considered

Salvage Therapy Scenarios

Fosfomycin may be reasonable as salvage therapy when:

• Fluoroquinolones cannot be used due to resistance (though resistance rates to fluoroquinolones for E. faecalis causing prostatitis in Korea were only 4.8-9.7% for levofloxacin/ciprofloxacin) 6
• Patient has documented allergies to preferred agents 2, 7
• Previous treatment failures with standard antibiotics 2
• The organism is susceptible to fosfomycin and no other oral options exist 4

Supporting Rationale

• Fosfomycin has in vitro activity against E. faecalis, including vancomycin-resistant strains 4
• Limited observational data show promising results for uncomplicated UTIs due to vancomycin-resistant enterococci 4
• Case reports describe successful treatment of chronic bacterial prostatitis with prolonged fosfomycin courses 7, 3
• A systematic review identified 73% clinical cure and 78% microbiological cure in chronic bacterial prostatitis across small cohort studies, though this represents low-quality evidence 3

Preferred Treatment Options

For E. faecalis prostatitis, prioritize:

• Fluoroquinolones (levofloxacin or ciprofloxacin) remain the preferred empirical agents due to low resistance rates (4.8-9.7%) and excellent prostate penetration 6
• Ampicillin is the drug of choice for enterococcal infections when susceptible 4
• High-dose ampicillin (18-30 g IV daily) or amoxicillin (500 mg PO/IV every 8 hours) can overcome resistance in urinary tract infections due to high urinary concentrations 4

Critical Caveats

Dosing Uncertainty

• No established dosing regimen exists for prostatitis 4, 2, 3
• Historical durations for acute bacterial prostatitis range from 14 days, while chronic bacterial prostatitis may require 6 weeks or longer 4
• Case reports describe prolonged courses (3 grams once daily for one week, then every two days for 3 months) 7, but this lacks validation
• Standard single 3-gram dose approved for cystitis is inadequate for prostatitis 1

Resistance Considerations

• Avoid tetracycline, erythromycin, and trimethoprim/sulfamethoxazole for E. faecalis prostatitis due to high resistance rates (97.5%, 95%, and 31.5% respectively) 6
• Fosfomycin susceptibility testing is not routinely performed in many laboratories, making empirical use problematic 4

Combination Therapy

• In vitro studies demonstrate synergistic or additive effects when fosfomycin is combined with linezolid, tigecycline, or gentamicin against vancomycin-resistant enterococci 4
• Consider combination therapy for serious infections, though clinical data are limited 4

In summary, reserve fosfomycin for E. faecalis prostatitis only when standard fluoroquinolones or ampicillin-based regimens cannot be used, and ensure documented susceptibility before initiating therapy.