What is the recommended antibiotic treatment for a patient with Enterococcus faecalis bacteremia?

Antibiotic Treatment for Enterococcus faecalis Bacteremia

Primary Recommendation

For uncomplicated E. faecalis bacteremia without endocarditis, treat with ampicillin monotherapy (2 g IV every 4-6 hours) for 7-14 days after catheter removal, reserving combination therapy for complicated cases or when endocarditis cannot be excluded. 1

Initial Assessment and Risk Stratification

Before selecting antibiotics, immediately determine:

• Catheter status: Remove short-term catheters immediately; remove long-term catheters if insertion site infection, suppurative thrombophlebitis, sepsis, or persistent bacteremia >72 hours despite appropriate therapy 1
• Endocarditis risk factors: New murmur, embolic phenomena, prosthetic valve, other endovascular foreign bodies, or bacteremia/fever persisting >72 hours on appropriate antibiotics warrant transesophageal echocardiography 1
• Susceptibility testing: Obtain MIC for ampicillin/penicillin and vancomycin, plus high-level aminoglycoside resistance (HLAR) testing for gentamicin (MIC >500 μg/mL) 1

Antibiotic Selection Based on Clinical Scenario

Uncomplicated Bacteremia (No Endocarditis)

Ampicillin 200 mg/kg/day IV in 4-6 divided doses (typically 2 g every 4-6 hours) for 7-14 days 1

• Ampicillin is the drug of choice for ampicillin-susceptible E. faecalis 1
• The role of adding gentamicin for uncomplicated catheter-related bloodstream infection without endocarditis is unresolved and generally not recommended due to nephrotoxicity risk without proven benefit 1
• Vancomycin 30 mg/kg/day IV in 2 divided doses (target trough 10-20 μg/mL) should be used only if ampicillin-resistant 1

Definite or Suspected Endocarditis

Ampicillin 200 mg/kg/day IV in 4-6 doses PLUS gentamicin 3 mg/kg/day IV in 1 dose for 2-6 weeks, followed by ampicillin alone to complete 4-6 weeks total 1

• Duration: 4 weeks for native valve with symptoms <3 months; 6 weeks for native valve with symptoms >3 months or prosthetic valve 1
• Some experts recommend limiting gentamicin to only 2 weeks to reduce nephrotoxicity while maintaining efficacy 1
• Monitor gentamicin levels and renal function at least weekly (twice weekly if renal impairment) 1

Alternative Regimen for Endocarditis (Avoiding Aminoglycosides)

Ampicillin 200 mg/kg/day IV in 4-6 doses PLUS ceftriaxone 4 g/day IV in 2 doses for 6 weeks 1, 2, 3

This combination is particularly valuable when:

• Patient has baseline renal insufficiency (creatinine clearance <50 mL/min) 1
• HLAR E. faecalis (gentamicin MIC >500 μg/mL) is present 1, 2
• Gentamicin causes nephrotoxicity during treatment 2, 3

Critical evidence: A multicenter study of 246 patients demonstrated ampicillin plus ceftriaxone was as effective as ampicillin plus gentamicin for E. faecalis endocarditis (mortality 22% vs 21%, p=0.81), but caused significantly less treatment discontinuation due to adverse events (1% vs 25%, p<0.001), primarily from renal failure (0% vs 23%, p<0.001) 2. This regimen works regardless of HLAR status 2.

Important limitation: This combination is NOT active against E. faecium, only E. faecalis 1

Ampicillin-Resistant E. faecalis

Vancomycin 30 mg/kg/day IV in 2 divided doses (target trough 10-20 μg/mL) PLUS gentamicin 3 mg/kg/day IV for 6 weeks 1

• If HLAR to gentamicin but susceptible to streptomycin, replace gentamicin with streptomycin 15 mg/kg/day in 2 divided doses 1
• If beta-lactamase production (rare), use ampicillin-sulbactam or amoxicillin-clavulanate 1

Multidrug-Resistant E. faecalis

For strains resistant to ampicillin, vancomycin, AND aminoglycosides:

Daptomycin 10-12 mg/kg/day IV PLUS ampicillin 200 mg/kg/day IV in 4-6 doses for ≥8 weeks 1, 4

• High-dose daptomycin (10-12 mg/kg/day) is essential for sustained bactericidal activity; standard doses (6-8 mg/kg/day) fail to maintain bacterial suppression 4
• Monitor CPK levels weekly due to myopathy risk at high doses 1, 4
• Alternative: Linezolid 600 mg IV/PO every 12 hours for ≥8 weeks (monitor hematological toxicity) 1

Critical Pitfalls to Avoid

• Never use cephalosporins as monotherapy for enterococcal infections due to intrinsic resistance 5
• Do not routinely add gentamicin for uncomplicated bacteremia without endocarditis—nephrotoxicity risk exceeds benefit 1, 2, 3
• Do not continue antibiotics beyond 7-14 days for uncomplicated catheter-related bacteremia after source control; prolonged therapy increases C. difficile and resistance risk 5
• Do not assume susceptibility to gentamicin—26-50% of E. faecalis strains have HLAR, rendering combination therapy ineffective 1, 5, 2
• Do not treat asymptomatic bacteriuria—treatment causes more harm than benefit 5
• Obtain repeat blood cultures at 48-72 hours to document clearance; persistent bacteremia >72 hours mandates TEE and consideration of endocarditis 1

Special Populations

Patients with Renal Impairment

• Prefer ampicillin plus ceftriaxone over ampicillin plus gentamicin for endocarditis to avoid aminoglycoside nephrotoxicity 1, 2, 3
• Adjust vancomycin dosing to maintain trough 10-20 μg/mL 1

Healthcare-Associated Infections

• Consider empiric VRE coverage with linezolid or daptomycin only for very high-risk patients (liver transplant recipients, known VRE colonization) 5
• De-escalate to ampicillin once susceptibility confirmed 5

Prosthetic Valve Endocarditis

• Always use combination therapy (ampicillin plus gentamicin or ampicillin plus ceftriaxone) for minimum 6 weeks 1
• Early surgical consultation is critical for optimizing outcomes 1

Monitoring During Therapy

• Renal function and gentamicin levels: Weekly (twice weekly if renal impairment) 1
• CPK levels: Weekly if using daptomycin 1, 4
• Repeat blood cultures: At 48-72 hours to document clearance 1
• Clinical reassessment: If fever/bacteremia persists >72 hours, perform TEE to exclude endocarditis 1