| PK/PD indices | Antibiotics | PK/PD thresholds associated with optimal bacterial killing and/or clinical outcome | PK/PD threshold for potential toxicity |
---|---|---|---|---|
Concentration-dependent with time-dependence | AUC0–24/MIC (AUIC) | Vancomycin | a) AUIC ≥ 400 (corresponds to trough concentrations of 15–20 mg/Lfor intermittent dosing; trough of 20–25 mg/L for continuous dosing) | Trough concentrations >27 mg/L with intermittent dosing |
b) trough concentrations >10Â mg/L to avoid development of resistance [16] | ||||
Linezolid | AUIC > 80 to 120 (corresponds to trough concentrations > 2 mg/L) [125, 156] | Has not been clearly defined | ||
Theoretical maximum trough concentrations threshold: 7–10 mg/L [120, 157, 158] | ||||
Recommended maximum: 7Â mg/L [158] | ||||
Fluoroquinolones | Â | |||
Aminoglycosides | Relation to therapeutic efficacy mainly shown in animal infection models | Â | ||
Daptomycin | AUIC > 666 [151] | Trough concentrations >24.3 mg/L [150] | ||
Concentration-dependent | Peak (Cmax)/MIC | Fluoroquinolones | Cmax/MIC >10 prevent emergent of resistant mutants in in vivo and in vitro models [137, 161, 162] | Â |
Aminoglycosides | Cmax/MIC 8–10 [163] | High dose extended-dosing: troughs undetectable or <1 mcg/mL | ||
Daptomycin | Cmax/MIC 59–94 [152] |  |