Daptomycin

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Background

  • Cyclic lipopeptide antibiotic that is active against Gram-positive bacteria

Mechanism of Action

  • Mechanism of action is to depolarize the cell membrane

Pharmacokinetics and Pharmacodynamics

  • Distributes well into soft tissues and musculoskeletal system, as well as urine
    • Poor CNS penetration1
    • Good lung penetration, but is inactivated by lung surfactant and should not be used to treat pneumonia
  • Bactericidal
  • Concentration-dependent, best predicted by AUC24:MIC

Dosing

  • Standard dose: 6 mg/kg IV q24h
  • High dose for severe infections, including MRSA bacteremia: 8 to 10 mg/kg IV q24h

Renal Dosing

GFR (mL/min) Routine Dose High Dose
>50 6 mg/kg IV q24h 8-10 mg/kg IV q24h
11-50 6-8 mg/kg IV q24h
≤10 8 mg/kg IV q48h
HD 8 mg/kg IV q48h, dosed after dialysis
CRRT 8 mg/kg IV q48h

References

  1. ^  S. Piva, Antonello Di Paolo, Laura Galeotti, Francesco Ceccherini, Francesco Cordoni, Liana Signorini, Tommaso Togni, Amedeo De Nicolò, Frank A. Rasulo, Nazzareno Fagoni, N. Latronico, Antonio D’Avolio. Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis. Neurocritical Care. 2019;31(1):116-124. doi:10.1007/s12028-018-0657-y.