Ceftaroline Should NOT Be Used for Enterococcal Infections
Ceftaroline has poor activity against Enterococcus and should not be used empirically or as monotherapy for VRE infections. 1 For serious enterococcal infections, daptomycin at high doses (10-12 mg/kg/day) is the preferred agent. 1
Daptomycin: The Preferred Agent for Serious Enterococcal Infections
Due to its bactericidal activity, daptomycin is preferred for the treatment of serious VRE infections at a dosing of at least 8 mg/kg and up to 10-12 mg/kg. 1
Optimal Daptomycin Dosing Strategy
- High-dose daptomycin 10-12 mg/kg/day IV produces sustained bactericidal activity and should be the standard approach for serious infections 2
- Standard doses of 8 mg/kg may be insufficient for some resistant strains 1
- Weekly CPK monitoring is mandatory during extended high-dose daptomycin therapy due to myopathy risk 2
The Role of Ceftaroline: Combination Therapy Only
While ceftaroline monotherapy is ineffective against enterococci, emerging evidence supports ceftaroline as a synergistic partner with daptomycin for resistant or persistent enterococcal infections. 2, 3, 4
When to Consider Daptomycin-Ceftaroline Combination
- Persistent bacteremia despite daptomycin monotherapy 2
- Enterococcal strains with high daptomycin MICs (≥3 μg/mL) within the susceptible range 2
- Daptomycin-nonsusceptible isolates 3
- Relapsed infections after initial daptomycin therapy 2
Mechanism of Synergy
- Ceftaroline enhances daptomycin binding to bacterial cell membranes 4
- The combination demonstrates greater bacterial reduction at 24 hours compared to daptomycin alone (P < 0.001) 4
- Ampicillin and ceftaroline in combination with daptomycin demonstrate the greatest synergistic activity compared with other β-lactam–daptomycin combinations 2
Specific Combination Dosing
- Daptomycin 10-12 mg/kg/day IV plus ceftaroline 600 mg IV every 12 hours for serious infections 2, 3
- If ampicillin-susceptible: Daptomycin 10-12 mg/kg/day IV plus ampicillin 2g IV every 6 hours (total 8g/day) is preferred over ceftaroline 2
Critical Clinical Pitfalls
Common Mistake: Using Ceftaroline as Monotherapy
- Ceftaroline exhibits broad-spectrum activity against Gram-positive bacteria but has poor activity against enterococcus 1
- This is a fifth-generation cephalosporin with excellent MRSA coverage but minimal enterococcal activity 5
- Ceftaroline is active in vitro against vancomycin-resistant E. faecalis (not E. faecium) 5, but clinical data supporting monotherapy are lacking
Daptomycin Monotherapy Failures
- Daptomycin failures have been documented in enterococcal infections, with some failures resulting from emergence of daptomycin-resistance during treatment 2
- There are insufficient data to recommend monotherapy with daptomycin for the treatment of multidrug-resistant enterococcal infections 2
- Combination therapy addresses this resistance emergence 2, 3, 4
Alternative Agents When Beta-Lactams Cannot Be Used
Linezolid
- Linezolid 600 mg PO or IV every 12 hours for 6 weeks is effective for chronic enterococcal infections with success rates of 80-86% 2
- Appropriate for monomicrobial VRE infections 1
- Weekly complete blood count monitoring required (>2 weeks) due to myelosuppression risk 2
Tigecycline
- Appropriate for polymicrobial VRE infections in intra-abdominal settings 1
- Should not be first-line in bacteremic patients due to poor plasma concentrations and higher risk of failing to clear bacteremia 1
Species-Specific Mortality Considerations
Vancomycin-resistant E. faecium infections are associated with higher mortality and longer duration of bacteremia compared to vancomycin-resistant E. faecalis infections. 1 This underscores the importance of:
- Aggressive combination therapy for E. faecium 2, 3, 4
- Cardiac surgery when indicated for endocarditis 1
- Source control measures including central catheter removal 1
Mandatory Infectious Disease Consultation
Management of relapsed or resistant enterococcal infections should involve infectious disease consultation as standard of care. 2 This ensures: