Background
Staphylococcus aureus1, 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 doses4, 5
– 4 to 6 mg/kg/day has higher rates of DNS S. aureus
– Experts recommend doses ≥ 8mg/kg/day especially for bacteremiahttps://jdc.jefferson.edu/pharmacyposters/1000/thumbnail.jp