Mechanism of Action:
Calcium-dependent binding/insertion of the lipophillic tail into gram-positive cyotplasmic membrane. Oligomerization/channel formation occurs with subsequent ion leakage and collapse of organism leading to cell death. (Figure 2)
AUC/MIC ratio predictive of pharmacodynamic activity.
Pharmacokinetics: (4mg/kg dose)
Cmax: 77.5mg/L; Half-life: 8 hours; Volume of distribution: 7L; Clearance (total): 8ml/h/kg
The most common adverse effects from this study were constipation (6.2%), nausea (5.8%), injection site reaction (5.8%) and headache (5.4%).
Intravenous only – available as 500 mg vials (powder for reconstitution)
Complicated skin and soft tissue infection – 4mg/kg every 24 hours
Doses studied in ongoing clinical trials for endocarditis and bacteremia are 6mg/kg every 24 hours
Disease state based dosing:
Hepatic failure: Not significantly altered in patients with hepatic impairment; no dosage adjustments in this population are necessary
Renal failure: In patients with an estimated CrCl < 40ml/min require a dosage adjustment of 4mg/kg every 48 hours.
Dosing during Continuous Renal Replacement Therapy
CVVH (Continuous venovenous hemofiltration): 4 or 6mg/kg IV q48h
CVVHD (Continuous venovenous hemodialysis): 4 or 6mg/kg IV q48h
CVVHDF (Continuous venovenous hemodiafiltration) 4 or 6mg/kg IV q48h
Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.
Limited data available.
Category B: No evidence of risk in humans but studies inadequate.
CPK levels should be monitored weekly. Daptomycin should be discontinued in patients with unexplained signs and symptoms of myopathy in conjuction with CPK elevation > 1000U/L, or in patients without reported symptoms who have marked elevations in CPK (>2000U/L).
Brand names/Manufacturer: Cubicin/Cubist pharmaceuticals