What is the recommended antimicrobial therapy and duration for Enterococcus faecalis infections, including options for beta‑lactam allergy and vancomycin‑resistant strains?

Antimicrobial Therapy for Enterococcus faecalis Infections

First-Line Treatment for Susceptible Strains

For ampicillin-susceptible E. faecalis, use ampicillin or penicillin G as monotherapy for most infections, reserving combination therapy with gentamicin only for endocarditis. 1

• Ampicillin 2g IV every 4-6 hours is the drug of choice for susceptible E. faecalis infections 1
• Vancomycin should be reserved for beta-lactam allergic patients, as beta-lactams are more rapidly bactericidal against susceptible strains 1
• Routine aminoglycoside combinations are no longer standard for non-endocarditis infections due to increasing resistance and nephrotoxicity concerns 1

Beta-Lactam Allergy Management

For patients with serious beta-lactam allergies, vancomycin is the appropriate alternative for susceptible E. faecalis. 1

• Vancomycin dosing should achieve therapeutic levels with appropriate monitoring 1
• Linezolid 600 mg IV or PO every 12 hours is an alternative option for beta-lactam allergic patients 1
• Daptomycin 8-12 mg/kg/day can be used but should ideally be combined with a beta-lactam if the allergy permits (e.g., cephalosporin in penicillin-allergic patients) 1, 2

Vancomycin-Resistant E. faecalis (VRE)

Linezolid 600 mg IV or PO every 12 hours is the strongest recommendation for vancomycin-resistant E. faecalis infections. 1, 3

• Linezolid demonstrated 81.4% clinical cure rates in the compassionate use program with 796 patients 1
• High-dose daptomycin 8-12 mg/kg/day, preferably combined with ampicillin or a carbapenem, is recommended for VRE bacteremia 1, 4
• The combination of daptomycin with beta-lactams (ampicillin, cephalosporins, or carbapenems) provides synergistic bactericidal activity even against beta-lactam resistant strains 1, 2
• Weekly CPK monitoring is mandatory with high-dose daptomycin due to myopathy risk 4

Site-Specific Treatment Durations

Uncomplicated Urinary Tract Infections

• Single-dose fosfomycin 3g PO for uncomplicated UTI due to VRE 1, 3
• Nitrofurantoin 100 mg PO every 6 hours for 5-7 days 1, 3
• High-dose ampicillin (18-30g IV daily in divided doses) or amoxicillin 500 mg every 8 hours for 7 days can overcome resistance in UTIs due to high urinary concentrations 1, 3

Bacteremia and Catheter-Related Infections

• 7-14 days of therapy for uncomplicated bacteremia with source control 1, 3
• Remove catheter within 72 hours when possible; if retained, extend therapy to 14 days with antibiotic lock therapy 1, 3
• Obtain transesophageal echocardiogram if bacteremia persists >72 hours after source control to rule out endocarditis 3

Endocarditis

• Native valve: 4-6 weeks of combination therapy (ampicillin or penicillin G plus gentamicin for the entire duration) 1, 3
• Prosthetic valve or prosthetic material: minimum 6 weeks of combination therapy 1, 3
• For VRE endocarditis, daptomycin 10-12 mg/kg/day combined with ampicillin (if susceptible) or ceftaroline for 6 weeks 4
• Gentamicin must be continued for the entire treatment course in enterococcal endocarditis, unlike streptococcal endocarditis where it's stopped after 2 weeks 3

Intra-abdominal Infections

• Tigecycline 100 mg IV loading dose, then 50 mg IV every 12 hours for VRE intra-abdominal infections, duration based on clinical response 1

Critical Resistance Testing Requirements

All E. faecalis isolates must be tested for ampicillin/penicillin susceptibility (MIC determination), vancomycin susceptibility, and high-level aminoglycoside resistance. 1

• High-level gentamicin resistance (>500 μg/mL) and streptomycin resistance (>1000 μg/mL) predict lack of synergy with cell wall-active agents 1
• For resistant strains, obtain daptomycin and linezolid susceptibility testing 1
• Approximately 26-50% of E. faecalis strains now demonstrate high-level aminoglycoside resistance, making combination therapy ineffective 1

Special Considerations and Pitfalls

Avoid vancomycin for routine treatment of beta-lactam susceptible E. faecalis, as it is less rapidly bactericidal than beta-lactams. 1

• Daptomycin monotherapy has documented treatment failures with emergence of resistance during therapy; combination with beta-lactams is strongly preferred 4
• Vancomycin tolerance (high MBC despite low MIC) can cause treatment failure despite in vitro susceptibility; consider high-dose daptomycin if suspected 5
• Do not treat asymptomatic bacteriuria with E. faecalis 3
• Infectious disease consultation is standard of care for all enterococcal endocarditis and relapsed infections 4, 3

Monitoring Requirements

• Weekly CPK levels during high-dose daptomycin therapy (>6 mg/kg) 4
• Weekly complete blood counts if using linezolid >2 weeks due to myelosuppression risk 4
• Renal function monitoring with aminoglycoside therapy 1
• Clinical response assessment at 5-7 days with microbiological documentation at 2-4 weeks 4