Combination Daptomycin and Vancomycin Therapy
Direct Answer
Yes, daptomycin and vancomycin can be given simultaneously to treat this polymicrobial infection, as there is no documented antagonism between these agents and they target different organisms with distinct susceptibility patterns. 1
Rationale for Combination Therapy
No Pharmacological Antagonism
- FDA labeling for daptomycin explicitly states that "antagonism, as determined by kill curve studies, has not been observed" when daptomycin is combined with other antibacterials in vitro. 1
- In vitro synergistic interactions of daptomycin with various antibacterials have been demonstrated against staphylococci and enterococci, with no evidence of antagonistic effects. 1
Organism-Specific Targeting
For Staphylococcus haemolyticus (vancomycin-susceptible only):
- Vancomycin 30-60 mg/kg/day IV divided every 6-12 hours with target trough levels of 15-20 mcg/mL is the primary treatment recommended by the Infectious Diseases Society of America. 2
- A loading dose of 25-30 mg/kg of vancomycin should be administered in seriously ill patients to rapidly achieve therapeutic levels. 2
- Daptomycin demonstrates in vitro activity against Staphylococcus haemolyticus, with at least 90% of isolates exhibiting MIC values within the susceptible range. 1
For Enterococcus faecium (daptomycin-susceptible only):
- Daptomycin 10-12 mg/kg per dose IV once daily for ≥6 weeks is recommended by the American Heart Association for multidrug-resistant enterococcal infections. 3
- The Clinical and Laboratory Standards Institute established a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL for E. faecium based on increased dosing of 8-12 mg/kg/day. 4
- Daptomycin exhibits rapid, concentration-dependent bactericidal activity against enterococci, including E. faecium. 1, 5
Dosing Recommendations
Vancomycin Dosing
- Administer 30-60 mg/kg/day IV divided every 6-12 hours. 2
- Give a loading dose of 25-30 mg/kg in seriously ill patients. 2
- Target trough concentrations of 15-20 mcg/mL. 3, 2
- Monitor trough levels closely and check renal function every 2-3 days. 2
Daptomycin Dosing
- Administer 10-12 mg/kg IV once daily for serious enterococcal infections. 3, 4
- Infuse over 30 minutes in adults (do NOT give as 2-minute push when using high doses). 1
- Monitor CPK levels weekly due to potential skeletal muscle effects. 1
Critical Monitoring Parameters
Renal Function
- Check serum creatinine every 2-3 days during vancomycin therapy. 2
- Adjust vancomycin dosing based on renal function to maintain therapeutic troughs. 3
- Daptomycin requires dose adjustment in patients with CrCl <30 mL/min. 1
Muscle Toxicity
- Monitor CPK levels weekly during daptomycin therapy. 1
- Discontinue daptomycin if CPK elevation is accompanied by signs/symptoms of myopathy. 1
Therapeutic Response
- Obtain repeat blood cultures to document clearance of bacteremia. 2
- Monitor inflammatory markers (ESR, CRP) to assess treatment response. 2
Important Caveats
Combination Enhancement Considerations
- While daptomycin-vancomycin combination is safe, β-lactam antibiotics (ampicillin, ceftaroline, ertapenem) demonstrate superior synergy with daptomycin against enterococci compared to vancomycin. 6, 7
- If the E. faecium isolate has any ampicillin susceptibility, consider daptomycin plus ampicillin instead of daptomycin plus vancomycin for enhanced bactericidal activity. 3, 6
Resistance Prevention
- The American Heart Association recommends against daptomycin monotherapy for multidrug-resistant enterococcal infections due to emergence of resistance during treatment. 3
- High-dose daptomycin (10-12 mg/kg/day) is essential when treating E. faecium to prevent resistance development. 3, 4