What is the recommended dose of Daptomycin (Cubicin) for treatment?

From the Guidelines

Daptomycin should be dosed at 4-6 mg/kg intravenously once daily for most infections, with higher doses of 8-12 mg/kg once daily recommended for more serious infections like bacteremia, endocarditis, or osteomyelitis, as supported by the Infectious Diseases Society of America guidelines 1.

Key Considerations

• For patients with normal renal function, no dose adjustment is needed, but for those with creatinine clearance less than 30 mL/min, including hemodialysis patients, the dose should be administered every 48 hours.
• Daptomycin should be infused over 30 minutes or given as a 2-minute intravenous injection for 2 mg/mL concentrations.
• Monitoring creatine phosphokinase (CPK) levels weekly is important as daptomycin can cause myopathy.

Mechanism and Spectrum

• The drug is effective against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and other resistant organisms.
• It works by disrupting bacterial cell membrane function, leading to rapid depolarization and cell death.

Important Warnings

• Daptomycin should not be used for pneumonia as it is inactivated by pulmonary surfactant.
• Concomitant use with statins should be avoided due to increased risk of myopathy, as noted in various guidelines and studies 1.

Clinical Use

• For hospitalized patients with complicated skin and soft tissue infections (cSSTI), daptomycin 4 mg/kg/dose IV once daily is recommended, as per the guidelines 1.
• For adults with uncomplicated bacteremia, daptomycin 6 mg/kg/dose IV once daily for at least 2 weeks is recommended, while for complicated bacteremia, 4–6 weeks of therapy is suggested, depending on the extent of infection 1.

From the FDA Drug Label

2.2 Dosage in Adults for cSSSI Administer daptomycin for injection 4 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days.

2.3 Dosage in Pediatric Patients (1 to 17 Years of Age) for cSSSI The recommended dosage regimens based on age for pediatric patients with cSSSI are shown in Table 1. Administer daptomycin for injection intravenously in 0. 9% sodium chloride injection once every 24 hours for up to 14 days Table 1: Recommended Dosage of Daptomycin for Injection in Pediatric Patients (1 to 17 Years of Age) with cSSSI, Based on Age Age Range Dosage Regimen* Duration of therapy 12 to 17 years 5 mg/kg once every 24 hours infused over 30 minutes Up to 14 days 7 to 11 years 7 mg/kg once every 24 hours infused over 30 minutes 2 to 6 years 9 mg/kg once every 24 hours infused over 60 minutes 1 to less than 2 years 10 mg/kg once every 24 hours infused over 60 minutes

2.4 Dosage in Adult Patients with Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates Administer daptomycin for injection 6 mg/kg to adult patients intravenously in 0. 9% sodium chloride injection once every 24 hours for 2 to 6 weeks.

2.5 Dosage in Pediatric Patients (1 to 17 Years of Age) with Staphylococcus aureus Bloodstream Infections (Bacteremia) The recommended dosage regimens based on age for pediatric patients with S. aureus bloodstream infections (bacteremia) are shown in Table 2. Administer daptomycin for injection intravenously in 0. 9% sodium chloride injection once every 24 hours for up to 42 days. Table 2: Recommended Dosage of Daptomycin for Injection in Pediatric Patients (1 to 17 Years of Age) with S aureus Bacteremia, Based on Age Age Range Dosage* Duration of therapy 12 to 17 years 7 mg/kg once every 24 hours infused over 30 minutes Up to 42 days 7 to 11 years 9 mg/kg once every 24 hours infused over 30 minutes 1 to 6 years 12 mg/kg once every 24 hours infused over 60 minutes

The recommended daptomycin dose is:

• For adults with cSSSI: 4 mg/kg once every 24 hours for 7 to 14 days
• For pediatric patients (1 to 17 years of age) with cSSSI:
  • 5 mg/kg once every 24 hours infused over 30 minutes for patients 12 to 17 years of age
  • 7 mg/kg once every 24 hours infused over 30 minutes for patients 7 to 11 years of age
  • 9 mg/kg once every 24 hours infused over 60 minutes for patients 2 to 6 years of age
  • 10 mg/kg once every 24 hours infused over 60 minutes for patients 1 to less than 2 years of age
• For adult patients with Staphylococcus aureus bloodstream infections: 6 mg/kg once every 24 hours for 2 to 6 weeks
• For pediatric patients (1 to 17 years of age) with Staphylococcus aureus bloodstream infections:
  • 7 mg/kg once every 24 hours infused over 30 minutes for patients 12 to 17 years of age
  • 9 mg/kg once every 24 hours infused over 30 minutes for patients 7 to 11 years of age
  • 12 mg/kg once every 24 hours infused over 60 minutes for patients 1 to 6 years of age 2

From the Research

Daptomycin Dosing Regimens

• The standard dose of daptomycin is 4 mg/kg intravenously every 24 hours for 7-14 days, as compared to conventional antibiotics in patients with complicated skin and skin-structure infections 3.
• A study suggested that a dose of 6 mg/kg every 24 hours may be sufficient for patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, with a target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio of >666 4.
• For patients with creatinine clearance >60 mL/min and MIC values of 1.0 mg/L, a dose of 10 mg/kg every 24 hours may be recommended 4.
• In patients with renal failure and undergoing continuous veno-venous hemodialysis (CVVHD), a dose of ≥ 4 mg/kg every 24 hours may be necessary to achieve effective antimicrobial plasma concentrations 5.

Special Considerations

• Daptomycin dosing interval may need to be increased to 2 days in patients with renal impairment 6.
• Patients with severe infections may require higher doses of daptomycin, such as 8-10 mg/kg 4.
• The emergence of resistance to daptomycin has been reported, highlighting the need for prospective surveillance 6.

Clinical Efficacy and Safety

• Daptomycin has been shown to be effective in treating complicated skin and skin-structure infections, as well as Staphylococcus aureus bacteraemia, including right-sided infective endocarditis 3, 7.
• Daptomycin is generally well tolerated, but concerns persist regarding potential muscle toxicity 6.
• The safety and efficacy of daptomycin were comparable to conventional therapy in patients with complicated skin and skin-structure infections 3.