What is the treatment for Enterococcus faecalis infections?

Treatment of Enterococcus faecalis Infections

Ampicillin 2g IV every 4-6 hours is the gold standard first-line treatment for susceptible Enterococcus faecalis infections, as most strains retain ampicillin susceptibility and this agent provides superior outcomes compared to alternatives. 1, 2

Treatment Selection by Infection Type

Uncomplicated Urinary Tract Infections

For uncomplicated lower UTIs caused by E. faecalis, you have several highly effective oral options:

• Nitrofurantoin 100 mg PO every 6 hours is recommended as first-line therapy, with excellent in vitro activity and high urinary concentrations 3, 2
• Fosfomycin 3g PO as a single dose is FDA-approved and effective for uncomplicated VRE UTIs 3, 2
• High-dose ampicillin (18-30g IV daily in divided doses) or amoxicillin 500mg PO/IV every 8 hours can overcome even ampicillin-resistant strains in UTIs due to high urinary drug concentrations, with clinical cure rates of 88.1% and microbiological eradication of 86% 3, 2

Critical caveat: Never use nitrofurantoin for pyelonephritis, complicated UTIs, or systemic infections due to inadequate tissue penetration, and avoid in patients with creatinine clearance <30-50 mL/min 2

Bacteremia and Serious Infections

For E. faecalis bacteremia or other serious systemic infections:

• Ampicillin 2g IV every 4 hours remains the drug of choice when the organism is susceptible (penicillin MIC ≤8 mg/L) 1, 2
• Add gentamicin for synergy in serious infections requiring bactericidal activity, particularly endocarditis, if the strain is not high-level aminoglycoside resistant 1, 2
• Double beta-lactam therapy (ampicillin plus ceftriaxone) offers comparable efficacy to ampicillin-gentamicin with significantly less nephrotoxicity for gentamicin-resistant strains 1, 2
• Treatment duration: 7-14 days for uncomplicated infections, 4-6 weeks minimum for endocarditis 1, 2

Endocarditis

For E. faecalis infective endocarditis:

• Ampicillin 2g IV every 4 hours combined with gentamicin for 4-6 weeks for native valve endocarditis 1, 2
• Prosthetic valve endocarditis requires a minimum of 6 weeks of treatment 1, 2
• Always obtain infectious disease consultation for enterococcal endocarditis management as standard of care 1
• E. faecalis endocarditis is associated with mitral valve infection, central venous lines, and liver transplantation 3

Vancomycin-Resistant E. faecalis (VRE)

When dealing with vancomycin-resistant strains (though only 3% of E. faecalis are multidrug-resistant, compared to 95% of E. faecium):

• Linezolid 600mg IV or PO every 12 hours is the preferred agent with strong recommendation, showing microbiological cure rates of 86.4% and clinical cure rates of 81.4% 3, 1
• High-dose daptomycin 8-12 mg/kg/day IV is preferred for serious VRE bacteremia, with bactericidal activity superior to linezolid for bloodstream infections 3, 2, 4
• Daptomycin plus beta-lactam combination (penicillins, cephalosporins, or carbapenems) is recommended for VRE bacteremia to enhance efficacy 3
• Linezolid showed lower mortality (32.8%) compared to daptomycin (35.7%) in pooled analyses, though significant heterogeneity existed 3

Chronic Prostatitis

For E. faecalis chronic bacterial prostatitis, which is challenging due to poor prostatic penetration:

• Linezolid 600mg PO every 12 hours as pulse therapy: 2 weeks on, 1 week off, to minimize myelosuppression and peripheral neuropathy risk 5
• Complete 2-3 cycles of pulse therapy if symptoms persist but are improving 5
• High-dose daptomycin (8-12 mg/kg/day) is an alternative for linezolid-intolerant patients, though prostatic penetration may be inferior 5

Critical Resistance Patterns and Pitfalls

Key distinction: E. faecalis and E. faecium have vastly different resistance profiles—only 3% of E. faecalis strains are multidrug-resistant versus up to 95% of E. faecium strains 1, 2

What NOT to Use:

• Never use cephalosporins alone for enterococcal coverage—they have no intrinsic activity despite in vitro synergy when combined with ampicillin 1
• Ceftaroline has poor activity against enterococci and should not be empirically used 3
• Avoid vancomycin empirically for E. faecalis when ampicillin is superior; reserve vancomycin for documented beta-lactam allergy 1
• Do not use tetracycline, erythromycin, clindamycin, or metronidazole—these show 53-100% resistance rates in clinical isolates 6, 7

Emerging Resistance Concerns:

• Non-susceptible isolates can emerge during therapy, particularly with inadequate dosing 4
• Resistance rates for chloramphenicol, fosfomycin, imipenem, linezolid, and quinupristin-dalfopristin are increasing over time globally 8
• Always differentiate colonization from true infection before initiating anti-enterococcal therapy to avoid unnecessary broad-spectrum antibiotic pressure 3, 1

Monitoring and Adjustment

• Verify the antibiogram and adjust therapy when culture and sensitivity results are available 1
• Check for clinical improvement within 48-72 hours; if absent, consider resistance or alternative diagnosis 1
• For ampicillin-resistant VRE in UTIs, high-dose ampicillin may still work due to urinary drug concentrations overcoming resistance 3
• Therapeutic drug monitoring for ampicillin and newer agents can optimize efficacy and minimize toxicity 9