What is the appropriate dosing and administration of Daptomycin (Cubicin) 500mg via intravenous (IV) administration for systemic infections caused by Gram-positive bacteria?

From the Guidelines

Daptomycin (Cubicin) 500mg should be administered at a dose of 8-12 mg/kg once daily by intravenous infusion for systemic infections caused by Gram-positive bacteria, including vancomycin-resistant enterococci (VRE) bloodstream infections, as recommended by the most recent guidelines 1. The dosing regimen may vary depending on the severity of the infection, with more serious infections like bacteremia or endocarditis requiring higher doses.

• The medication should be reconstituted with 0.9% sodium chloride and infused over 30 minutes.
• The typical duration of therapy ranges from 7-14 days for skin infections and 2-6 weeks for bacteremia or endocarditis, depending on clinical response.
• Dosage adjustments are necessary for patients with creatinine clearance below 30 mL/min (use 4-6 mg/kg every 48 hours).
• Monitor creatine phosphokinase (CPK) levels weekly during treatment as daptomycin may cause muscle toxicity.
• Daptomycin works by disrupting bacterial cell membrane function, leading to rapid depolarization and cell death, which provides effective bactericidal activity against resistant organisms like MRSA and VRE.
• The once-daily dosing regimen enhances patient compliance while maintaining efficacy against serious Gram-positive infections.
• A clinical assessment to identify the source and extent of the infection with elimination and/or debridement of other sites of infection should be conducted 1.
• Additional blood cultures 2–4 days after initial positive cultures and as needed thereafter are recommended to document clearance of bacteremia 1.
• Echocardiography is recommended for all adult patients with bacteremia, with transesophageal echocardiography (TEE) preferred over transthoracic echocardiography (TTE) 1. The most recent study 1 provides the highest quality evidence for the dosing and administration of daptomycin, and its recommendations should be prioritized in clinical practice.

From the FDA Drug Label

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 appropriate dosing and administration of Daptomycin (Cubicin) 500mg via intravenous (IV) administration for systemic infections caused by Gram-positive bacteria is as follows:

• Dosage: 4 mg/kg once every 24 hours for complicated skin and skin structure infections (cSSSI) and 6 mg/kg once every 24 hours for S. aureus bacteremia.
• Administration: Administer intravenously in 0.9% sodium chloride, either by injection over a 2-minute period or by infusion over a 30-minute period.
• Renal Impairment: For patients with creatinine clearance <30 mL/min, including hemodialysis and CAPD, the dosage regimen is 4 mg/kg once every 48 hours for cSSSI and 6 mg/kg once every 48 hours for S. aureus bacteremia.
• Reconstitution and Storage: Reconstitute the 500mg vial with 0.9% sodium chloride injection to a concentration of 50 mg/mL, and administer within 12 hours at room temperature or 48 hours under refrigeration 2.

From the Research

Daptomycin (Cubicin) 500mg Administration

• Daptomycin is approved for the treatment of complicated skin and soft tissue infections (cSSTI) and Staphylococcus aureus right-sided infective endocarditis (RIE) and bacteremia associated with cSSTI and RIE at doses of 4 mg/kg/day and 6 mg/kg/day, respectively 3, 4.
• The appropriate dosing and administration of Daptomycin (Cubicin) 500mg via intravenous (IV) administration for systemic infections caused by Gram-positive bacteria is typically 4-6 mg/kg/day, with some studies suggesting the use of higher doses (>6 mg/kg/day) for difficult-to-treat infections 5, 6.
• The administration of Daptomycin should be done as a once-daily intravenous infusion, with the dose adjusted based on the patient's renal function and the severity of the infection 7, 3.

Special Considerations

• In patients with acute kidney injury (AKI) undergoing extended dialysis, a daily dose of 6 mg/kg daptomycin may be necessary to avoid underdosing 7.
• High-dose daptomycin (>6 mg/kg/day) has been shown to be effective and well-tolerated in patients with difficult-to-treat Gram-positive infections, including osteomyelitis, foreign body/prosthetic infection, and endocarditis 5, 6.

Key Points

• Daptomycin has a unique mechanism of action and a relatively prolonged concentration-dependent postantibiotic effect in vitro 3.
• Daptomycin is effective against a wide variety of Gram-positive bacteria, including meticillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci 3, 4.
• The use of high-dose daptomycin, alone or in combination with other antibiotics, may be useful for difficult-to-treat Gram-positive infections, and further evaluation of these strategies is warranted 5, 6.