What antibiotics should I give for an adult with a blood culture positive for Enterococcus faecalis?

Treatment of Enterococcus faecalis Bacteremia

For blood cultures positive for Enterococcus faecalis, start ampicillin 2 g IV every 4 hours plus gentamicin 3 mg/kg/day IV in 3 divided doses, pending susceptibility results. 1, 2

Initial Empiric Therapy

• Ampicillin is the gold standard first-line agent for E. faecalis because most strains (97%) remain ampicillin-susceptible, unlike E. faecium which has intrinsic penicillin resistance 2
• Add gentamicin for synergistic bactericidal activity in serious bloodstream infections 1
• Target gentamicin peak levels of 3-4 μg/mL and trough <1 μg/mL 1

Duration of Therapy Based on Source

For uncomplicated bacteremia without endocarditis:

• Treat for 10-14 days 3

If endocarditis is present or suspected:

• Native valve: 4-6 weeks depending on symptom duration before diagnosis (4 weeks if <3 months of symptoms, 6 weeks if ≥3 months) 1
• Prosthetic valve: minimum 6 weeks 1

Alternative Regimens When Standard Therapy Cannot Be Used

For patients with penicillin allergy (documented by skin testing):

• Vancomycin 30 mg/kg/day IV in 2 divided doses (target trough 10-20 μg/mL) plus gentamicin 3 mg/kg/day for 6 weeks 1
• Note: Ampicillin-gentamicin is superior to vancomycin-gentamicin and has lower nephrotoxicity/ototoxicity risk 1
• Consider penicillin desensitization for true life-threatening infections requiring optimal therapy 4

For high-level aminoglycoside resistance (HLAR):

• Ampicillin 200 mg/kg/day IV in 4-6 divided doses PLUS ceftriaxone 2 g IV every 12 hours for 6 weeks 1
• This double β-lactam regimen avoids aminoglycoside toxicity and is equally effective 1
• The ampicillin-ceftriaxone combination showed no nephrotoxicity versus 23% with ampicillin-gentamicin 1

For streptomycin-susceptible, gentamicin-resistant strains:

• Ampicillin 2 g IV every 4 hours plus streptomycin 15 mg/kg/day IV or IM in 2 divided doses (target peak 20-35 μg/mL, trough <10 μg/mL) 1
• Avoid streptomycin if creatinine clearance <50 mL/min due to irreversible ototoxicity risk 1

For β-lactamase-producing E. faecalis (rare):

• Ampicillin-sulbactam 3 g IV every 6 hours plus gentamicin 1

Critical Monitoring Parameters

• Renal function and aminoglycoside levels must be monitored closely, especially in elderly patients (median age 70 years in major trials) 1
• Consider shortening gentamicin to 2 weeks in patients with baseline renal impairment (creatinine clearance 30-50 mL/min) to reduce nephrotoxicity 1
• Monitor vancomycin troughs if used (target 10-20 μg/mL) 1

Common Pitfalls to Avoid

• Never use cephalosporins alone for enterococcal coverage—they have no intrinsic activity against enterococci 2
• Do not assume E. faecium has the same susceptibility as E. faecalis—E. faecium requires vancomycin or linezolid due to intrinsic ampicillin resistance 2
• Do not empirically use vancomycin for E. faecalis when ampicillin can be used—ampicillin is superior and vancomycin should be reserved for documented β-lactam allergy 2
• Verify susceptibilities when available and adjust therapy accordingly 2

When to Suspect Endocarditis

• Obtain infectious disease and cardiology consultation if bacteremia persists >72 hours, patient has prosthetic valve material, or has new cardiac murmur 1
• Echocardiography (transesophageal preferred) should be performed to rule out endocarditis in persistent bacteremia 1
• E. faecalis bacteremia carries 11% mortality but can reach 50% in severely ill patients 5