Daptomycin Dosing for Enterococcus faecalis Abdominal Wound Infection
Recommended Dosage
For a complicated Enterococcus faecalis abdominal wound infection not responding to oral amoxicillin, use high-dose daptomycin 8-12 mg/kg IV daily combined with ampicillin 2g IV every 6 hours (if susceptible), rather than daptomycin monotherapy. 1, 2
Rationale for Combination Therapy Over Monotherapy
The American Heart Association explicitly states there are insufficient data to recommend daptomycin monotherapy for multidrug-resistant enterococcal infections, with documented treatment failures including emergence of daptomycin-resistance during therapy. 1 Key evidence supporting combination therapy includes:
Ampicillin plus daptomycin demonstrates superior synergistic bactericidal activity compared to daptomycin alone, with adjusted hazard ratios of 19.01 (p=0.002) for survival compared to monotherapy. 1
Daptomycin monotherapy shows inferior outcomes in bloodstream infections, which have more published data than intra-abdominal infections. 1
The American Heart Association recommends combination therapy with daptomycin and ampicillin (Class IIb, Level of Evidence C) especially for patients with persistent bacteremia or enterococcal strains with high MICs (≥3 μg/mL) to daptomycin. 1
Specific Dosing Protocol
For Ampicillin-Susceptible E. faecalis:
- Daptomycin 10-12 mg/kg IV once daily 1, 3
- Plus ampicillin 2g IV every 6 hours (total 8g/day) 1, 2
- Treatment duration: Continue until clinical improvement and source control achieved, typically 7-14 days for complicated intra-abdominal infections 2
For Ampicillin-Resistant Strains:
- Linezolid 600 mg IV or PO every 12 hours is preferred over daptomycin monotherapy 1, 2
- Alternative: High-dose daptomycin 10-12 mg/kg combined with ceftaroline (demonstrates synergistic activity) 1
Critical Monitoring Requirements
Weekly CPK monitoring is mandatory during high-dose daptomycin therapy due to myopathy risk. 1 In a multicenter study of 245 patients receiving high-dose daptomycin (median 8.2 mg/kg/day), only 3% developed CPK elevation, all were asymptomatic, and no regimens were discontinued due to elevated CPK. 3
Susceptibility Testing Considerations
Obtain comprehensive susceptibility testing including:
- Ampicillin/penicillin MIC determination 1
- Daptomycin MIC (critical for treatment decisions) 4
- Vancomycin susceptibility 1
Higher daptomycin MICs (3-4 mg/L) are associated with treatment failure (OR=3.23, p=0.013) even with combination therapy, making combination therapy especially critical at these MIC levels. 1, 5
Clinical Efficacy Data
In a multicenter cohort of 245 patients with enterococcal infections (including 14% intra-abdominal infections) treated with high-dose daptomycin:
- Clinical success rate: 89% (193/218 patients) 3
- Microbiological eradication: 93% (177/191 patients) 3
- Median time to blood culture clearance: 3 days 3
- Only 2% developed daptomycin-nonsusceptible strains during therapy 3
Important Clinical Pitfalls to Avoid
Do not use standard-dose daptomycin (6 mg/kg/day) for complicated enterococcal infections—higher doses (10-12 mg/kg/day) are required for adequate efficacy. 2, 4
Do not use cephalosporins or aminoglycosides as monotherapy as they have minimal activity against enterococci and lead to high rates of treatment failure. 2
Ensure adequate source control of the abdominal wound infection—failure to achieve source control will likely result in treatment failure regardless of antibiotic choice. 2
Infectious Disease Consultation
Management of complicated enterococcal infections should involve infectious disease consultation as standard of care, particularly for patients not responding to initial therapy or requiring prolonged treatment. 1