What is the dose of daptomycin for IV push administration?

Daptomycin IV Dosing

For IV administration, daptomycin should be dosed at 6 mg/kg once daily for bacteremia and right-sided endocarditis, or 8-10 mg/kg once daily for left-sided endocarditis and complicated MRSA infections, administered as a 30-minute infusion every 24 hours. 1

Standard FDA-Approved Dosing

• The FDA-approved dose is 6 mg/kg IV once every 24 hours for S. aureus bacteremia and right-sided endocarditis. 2, 1
• Treatment duration is 2 weeks for uncomplicated bacteremia, or 4-6 weeks for complicated bacteremia or endocarditis. 2, 1
• For complicated skin and soft tissue infections, the approved dose is 4 mg/kg IV once daily. 2

Expert-Recommended Higher Dosing (Off-Label)

• For left-sided endocarditis and complicated MRSA infections, expert consensus recommends 8-10 mg/kg IV once daily, which may reduce treatment-emergent resistance. 2, 1
• Higher doses (8-10 mg/kg) are generally well tolerated and not associated with excess toxicities compared to standard dosing. 2, 1
• In pediatric patients under 6 years of age, the recommended dose is 10 mg/kg IV once daily. 2

Administration Details

• Daptomycin must be administered as an IV infusion over 30 minutes, not as an IV push. 3, 4
• Once-daily dosing is essential because more frequent dosing intervals are associated with increased skeletal muscle adverse effects and elevated creatine phosphokinase levels. 5
• The drug exhibits concentration-dependent bactericidal activity, making once-daily dosing pharmacodynamically optimal. 3, 5

Critical Contraindications

• Daptomycin is absolutely contraindicated for pneumonia treatment due to inhibition by pulmonary surfactant. 2, 1
• However, it remains effective for septic pulmonary emboli from bacteremia, as this represents a distinct pathogenesis from aspiration pneumonia. 2, 1

Combination Therapy Guidance

• Do not add gentamicin to daptomycin for bacteremia or native valve endocarditis—it provides no benefit and may prolong bacteremia. 2, 1
• Similarly, rifampin addition to daptomycin for bacteremia or native valve endocarditis is not recommended. 2
• For prosthetic valve endocarditis, combination therapy with vancomycin, gentamicin, and rifampin may be considered, but daptomycin monotherapy is preferred for native valve disease. 2

Important Clinical Considerations

• Daptomycin demonstrates dose-proportional pharmacokinetics with a half-life of approximately 8 hours and 90-93% protein binding. 6
• Monitor creatine phosphokinase (CPK) levels during therapy, though clinically significant elevations with muscle symptoms occur in only 0.2% of patients. 4
• Treatment-emergent resistance can develop in approximately 5% of patients, particularly when surgical debridement of deep-seated infections is needed but not performed. 2
• Use caution when treating vancomycin-resistant isolates or after prior glycopeptide therapy, as cross-resistance may occur due to shared target sites. 5