What is the recommended treatment for patients at risk of Enterococcus faecium or Enterococcus faecalis endocarditis?

Risk of Enterococcus faecalis and faecium Causing Endocarditis

Enterococcus species are among the leading causes of infective endocarditis worldwide, with E. faecalis accounting for the majority of enterococcal endocarditis cases, while E. faecium represents a smaller but increasingly problematic proportion due to its higher rates of multidrug resistance. 1

Species-Specific Endocarditis Risk

E. faecalis

• E. faecalis is one of the main causes of infective endocarditis globally, typically affecting elderly and fragile populations with high mortality rates 1
• E. faecalis is the predominant enterococcal species in antibiotic-naive patients and represents the majority of enterococcal endocarditis cases 2
• Most E. faecalis strains remain vancomycin-susceptible (VSE), making them generally more treatable than E. faecium 2

E. faecium

• E. faecium is significantly more likely to be multidrug-resistant compared to E. faecalis, with up to 95% of vancomycin-resistant strains expressing multiple resistance patterns 3, 4
• E. faecium typically shows higher minimum inhibitory concentrations (MICs) to beta-lactams than E. faecalis due to altered penicillin-binding protein 5 (PBP5) 4
• Five phenotypes of vancomycin resistance (vanA through vanE) exist, with vanA and vanB genes found primarily in E. faecium 3

High-Risk Patient Populations for Enterococcal Endocarditis

Empiric anti-enterococcal therapy should be directed at patients with specific risk factors, including:

• Patients with valvular heart disease or prosthetic intravascular materials 5
• Immunocompromised patients, particularly transplant recipients 5, 6
• Patients with health care-associated infections, especially postoperative infections 5
• Patients who have previously received cephalosporins or other antimicrobial agents that select for Enterococcus species 5
• Liver transplant recipients with hepatobiliary infections are at very high risk for vancomycin-resistant E. faecium 5
• Patients known to be colonized with vancomycin-resistant E. faecium 5

Treatment Implications Based on Resistance Patterns

For Ampicillin-Susceptible Strains

• Ampicillin 200 mg/kg/day IV plus gentamicin 3 mg/kg/day IV/IM is the gold standard for beta-lactam and gentamicin-susceptible enterococci 5, 4
• Native valve endocarditis requires 4-6 weeks depending on symptom duration, while prosthetic valve endocarditis requires minimum 6 weeks 5, 4

For High-Level Aminoglycoside Resistance (HLAR)

• The dual beta-lactam regimen of ampicillin 200 mg/kg/day IV plus ceftriaxone 4g/day IV for 6 weeks is the treatment of choice for HLAR E. faecalis 5, 4
• This combination is active against E. faecalis with and without HLAR but is NOT active against E. faecium 5
• The major advantage is lower nephrotoxicity risk compared to aminoglycoside-containing regimens 5

For Vancomycin-Resistant Enterococci (VRE)

• Linezolid 600 mg IV/PO every 12 hours is FDA-approved and recommended for vancomycin-resistant E. faecium infections, including concurrent bacteremia 3, 7
• Linezolid has 97-99% susceptibility rates for multiresistant E. faecium strains and achieved 77% cure rates in VRE endocarditis 3
• Daptomycin 10-12 mg/kg/day IV plus ampicillin 200 mg/kg/day IV for ≥8 weeks is the preferred combination therapy for severe VRE endocarditis 3, 4
• High-dose daptomycin (12 mg/kg IV daily) has demonstrated efficacy even in vancomycin-tolerant E. faecalis strains 2

Critical Pitfalls to Avoid

• Enterococci are intrinsically resistant to cephalosporins when used as monotherapy 3
• Vancomycin monotherapy is inadequate for enterococcal endocarditis; it must be combined with an aminoglycoside 8
• Quinupristin-dalfopristin is NOT active against E. faecalis, only E. faecium 5, 4
• Monitor for bone marrow suppression and neuropathy with prolonged linezolid use (>28 days) 3, 7
• Streptomycin should be avoided in patients with creatinine clearance <50 mL/min 5
• Aminoglycoside levels and renal function must be monitored weekly (twice weekly in renal failure) 5, 4
• Vancomycin trough levels should be maintained ≥20 mg/L with AUC/MIC >400 for optimal efficacy 5, 4