What is the preferred combination therapy for serious Enterococcus (E.) faecalis infections?

Preferred Combination Therapy for Serious Enterococcus faecalis Infections

The preferred combination therapy for serious Enterococcus faecalis infections is ampicillin plus gentamicin, which remains the gold standard treatment for susceptible strains. 1

First-line Therapy Options

For susceptible E. faecalis strains:

• Ampicillin (2g IV every 4h) plus gentamicin (3mg/kg/day IV divided into 3 doses) is the standard combination therapy for serious E. faecalis infections including infective endocarditis 1
• Treatment duration is typically 4-6 weeks for native valve endocarditis and at least 6 weeks for prosthetic valve endocarditis 1
• Unlike streptococcal infections, aminoglycoside therapy should continue for the entire treatment course in enterococcal infections 1

Alternative Combination Therapy

For aminoglycoside-resistant E. faecalis:

• Ampicillin (2g IV every 4h) plus ceftriaxone (2g IV every 12h) has emerged as an effective alternative combination 1
• This combination is particularly valuable for patients with renal impairment or those at high risk of aminoglycoside toxicity 1
• Six weeks of therapy is recommended regardless of symptom duration when using this regimen 1

For penicillin-allergic patients:

• Vancomycin (30mg/kg/day IV in 2 divided doses) plus gentamicin (3mg/kg/day IV in 3 divided doses) for 6 weeks 1
• Note that vancomycin-gentamicin combinations may have increased risk of ototoxicity and nephrotoxicity compared to penicillin-gentamicin combinations 1

Special Considerations for Resistant Strains

For vancomycin-resistant E. faecalis:

• Daptomycin (10-12 mg/kg/day IV) is preferred for serious vancomycin-resistant enterococcal infections 1
• Linezolid (600mg IV or orally every 12h) is an alternative option 1
• Combination therapy with daptomycin plus ampicillin or ceftaroline should be considered, especially for persistent bacteremia 1

For β-lactamase-producing strains:

• Ampicillin-sulbactam plus gentamicin is recommended 1

Synergistic Mechanisms

• The combination of ampicillin and gentamicin demonstrates synergistic bactericidal activity against E. faecalis 2
• Enterococci are intrinsically resistant to aminoglycosides when used alone, but the cell wall-active agent (ampicillin) facilitates aminoglycoside entry into the bacterial cell 2
• Similarly, the ampicillin-ceftriaxone combination shows synergistic activity despite enterococci being resistant to ceftriaxone when used as monotherapy 1

Management Recommendations

• All patients with enterococcal infective endocarditis should be managed by specialists in infectious diseases 1
• Susceptibility testing is crucial as resistance patterns vary significantly between E. faecalis and E. faecium (with E. faecium generally being more resistant) 3
• E. faecalis infections are associated with lower mortality rates compared to E. faecium (11% vs 50%), but still require aggressive combination therapy 4

Pitfalls and Caveats

• Monitoring for aminoglycoside toxicity is essential; gentamicin serum levels should be adjusted to achieve peak concentrations of 3-4 μg/mL and trough concentrations <1 μg/mL 1
• Streptomycin should be avoided in patients with creatinine clearance <50 mL/min 1
• Unlike treatment for streptococcal infections, single daily dosing of aminoglycosides is not recommended for enterococcal infections 1
• Vancomycin should only be used when patients cannot tolerate β-lactams or when the organism is resistant to penicillin but susceptible to vancomycin 1

By following these evidence-based combination therapy approaches, clinicians can optimize outcomes for patients with serious E. faecalis infections while minimizing treatment-related complications.