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  Daptomycin Non-Susceptible MRSA Bacteremia: A Case Report

  Jaclyn Cusumano, PharmD; Anna Marie Morlino, PharmD; and Andrew Moyer, PharmD

  Background

  Staphylococcus aureus^{1, 2, 3}

  • One of the most common pathogens causing community-acquired and nosocomial infections
  • Has rapidly developed resistance to many antibiotics:

  Daptomycin ²

  • Bactericidal cyclic lipopeptide antibiotic
  • Possesses negative charge which attracts calcium to form cationic complex
  • Interacts with negatively charged phospholipid heads on bacterial cell membranes, leading to membrane depolarization and cell death

  Daptomycin non-susceptible (DNS) S. aureus ^{2, 4, 5}

  • Extremely rare - About 60 clinical cases reported
  • Defined by an MIC greater than 1 mcg/mL
  • Potential mechanisms include:

  – Changes in cell membrane and cell wall structure alter daptomycin’s permeability²

  • Overexpression and dysregulation of dltA transcription increases D-alanylated teichoic acid content in the cell wall
  • mprF mutation leads to partially neutral charge of cell membrane

  – Vancomycin intermediate S. aureus (VISA) and vancomycin resistant S. aureus (VRSA) may predispose patients to develop DNS S. aureus²

  • Have seen increased resistance with lower doses^{4, 5}

  – 4 to 6 mg/kg/day has higher rates of DNS S. aureus

  – Experts recommend doses ≥ 8mg/kg/day especially for bacteremia