What are the recommended doses of Daptomycin and Ceftaroline (Ceftaroline) for treating complicated Gram-positive infections, particularly in patients with Impaired renal function?

From the Guidelines

For complicated Gram-positive infections, the recommended dose of Daptomycin is 8-12 mg/kg IV once daily, and Ceftaroline is typically dosed at 600 mg IV every 12 hours, with adjustments for renal impairment as follows: for Daptomycin, administer every 48 hours for creatinine clearance (CrCl) <30 mL/min, and for Ceftaroline, dose adjustments are CrCl 30-50 mL/min: 400 mg every 12 hours; CrCl 15-30 mL/min: 300 mg every 12 hours; CrCl <15 mL/min: 200 mg every 12 hours, with 200 mg given after dialysis sessions for hemodialysis patients 1.

Key Considerations for Dosing

• Daptomycin dosing is based on recent evidence suggesting high-dose therapy (8-12 mg/kg daily) may be effective for treating vancomycin-resistant enterococci bloodstream infections (VRE-BSI) without a significant increase in creatine kinase (CK) elevations 1.
• Ceftaroline, a fifth-generation cephalosporin, exhibits broad-spectrum activity against Gram-positive bacteria but has poor activity against enterococcus and should not be empirically used for the treatment of VRE infections 1.

Renal Impairment Adjustments

• For patients with impaired renal function, adjusting the frequency of Daptomycin administration is crucial to prevent drug accumulation and potential toxicity 1.
• Ceftaroline dose adjustments for renal impairment are necessary due to its primary elimination by the kidneys, similar to Daptomycin 1.

Monitoring and Safety

• Regular monitoring of renal function is essential during treatment with both antibiotics to ensure proper dose adjustments and minimize the risk of toxicity 1.
• For Daptomycin, weekly checks of creatine phosphokinase (CPK) levels are recommended to detect potential muscle toxicity, especially when using high-dose regimens 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Adult Patients Administer to adult patients intravenously in 0.9% sodium chloride, either by injection over a 2-minute period or by infusion over a 30-minute period. Recommended dosage regimen for adult patients: Creatinine Clearance (CL CR) Dosage Regimen cSSSI For 7 to 14 days S. aureus Bacteremia For 2 to 6 weeks ≥30 mL/min 4 mg/kg once every 24 hours 6 mg/kg once every 24 hours <30 mL/min, including hemodialysis and CAPD 4 mg/kg once every 48 hours* 6 mg/kg once every 48 hours*

The recommended dose of Daptomycin for treating complicated Gram-positive infections is:

• For adult patients with cSSSI: 4 mg/kg once every 24 hours for patients with creatinine clearance (CL CR) ≥30 mL/min, and 4 mg/kg once every 48 hours for patients with CL CR <30 mL/min.
• For adult patients with S. aureus bacteremia: 6 mg/kg once every 24 hours for patients with CL CR ≥30 mL/min, and 6 mg/kg once every 48 hours for patients with CL CR <30 mL/min.

However, the provided drug label does not contain information about Ceftaroline. The FDA drug label does not answer the question about Ceftaroline.

From the Research

Daptomycin and Ceftaroline Dosing

• The recommended dose of Daptomycin for complicated skin and soft-tissue infections is 4 mg/kg and for Staphylococcus aureus bacteraemia is 6 mg/kg 2.
• For patients with impaired renal function, the dose of Daptomycin should be adjusted, with a recommended dose of 4 mg/kg/48h for skin and soft tissue infections and 6 mg/kg/48h for bacteremia and right endocarditis in patients with creatinine clearance (CrCl) < 30 ml/min 3.
• Ceftaroline is usually administered intravenously at 600 mg every 12 h, but requires dose adjustments in individuals with renal failure 4.
• Daptomycin has been shown to be effective and well-tolerated in patients with renal impairment, with clinical and microbiologic success rates comparable to those in patients with normal renal function 5.
• In patients with acute kidney injury undergoing extended dialysis, a daily dose of 6 mg/kg Daptomycin may be necessary to avoid underdosing 6.

Renal Impairment Considerations

• Daptomycin is excreted by the kidneys and requires dose adjustments in patients with renal impairment 5, 3.
• Ceftaroline also requires dose adjustments in patients with renal failure 4.
• Patients with severe renal failure may have decreased renal clearance and increased elimination half-life of Daptomycin 3.
• Hemodialysis patients may have higher rates of clinical failure with Daptomycin 3.

Dosage Recommendations

• Daptomycin: 4 mg/kg/48h for skin and soft tissue infections and 6 mg/kg/48h for bacteremia and right endocarditis in patients with CrCl < 30 ml/min 3.
• Ceftaroline: 600 mg every 12 h, with dose adjustments for renal failure 4.
• Daptomycin in patients with acute kidney injury undergoing extended dialysis: 6 mg/kg daily 6.