daptomycin

resistant gram-positive specialist

Cyclic lipopeptide for MRSA/VRE refractory to vancomycin. Bactericidal. Ineffective in pneumonia (inactivated by surfactant).

• mechanism: ${\text{Ca}}^{2+}$-dependent binding to cell membrane $\to$ depolarisation $\to$ $K^{+}$ efflux $\to$ cell death.
• spectrum: Gram-positives ONLY (MRSA, VRE, MDR streptococci).

dosing (local policy)

Standard dosing based on CrCl > 30 mL/min. Use Adjusted Body Weight (AdjBW) for obesity.

• Skin/Soft Tissue: 4–6 mg/kg IV q24h.
• Bacteraemia / Infective Endocarditis: 8–10 mg/kg IV q24h.
• E. faecium (VRE): 10–12 mg/kg IV q24h.

renal adjustments

• CrCl < 30 mL/min: Administer standard dose q48h.
• Intermittent Haemodialysis (IHD):
  • Load with weight-based dose x 1.
  • Maintenance: Dose post-dialysis (3x weekly).
• Peritoneal Dialysis (PD): Standard dose IV q48h.
• CRRT (CVVHD/F): 4–8 mg/kg IV q24h.
  • Note: May consider up to 10 mg/kg depending on flow rates/residual function.

indications

• S. aureus bacteraemia (including right-sided endocarditis).
• Complicated Skin & Soft Tissue Infections (cSSTI).
• VRE infections (E. faecium).

cautions

pulmonary inactivation

NEVER use for pneumonia. Daptomycin is inactivated by pulmonary surfactant.

• Myopathy / Rhabdomyolysis:
  • Monitor CK weekly.
  • Guideline: Monitor CK/symptoms more frequently if dose > 8 mg/kg.
  • Consider holding concomitant statins.
  • Stop if CK > 5x ULN (asymptomatic) or > 10x ULN (symptomatic).
• Eosinophilic Pneumonia: Rare. Presents > 2 weeks into therapy (fever, dyspnoea, new infiltrates).
• Lab Interference: Can cause false elevation of INR (interaction with assay).

special considerations

clinical pearl

For high-inoculum infections (e.g., endocarditis), doses < 8 mg/kg are associated with treatment failure and emergence of resistance. Don’t underdose.

• Resistance: Non-susceptibility can emerge during therapy (check repeat cultures if persistent bacteraemia).

related pages: Vancomycin, Linezolid, Infective Endocarditis