Table 3.
Summary of concentration-dependent with time-dependence and concentration-dependent antibiotics, and proposed targets for TDM dose adjustments
| 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 >10 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: 7 mg/L [158] | ||||
| Fluoroquinolones | AUIC > 125 for Gram negative organisms [137, 159, 160] | |||
| Aminoglycosides | Relation to therapeutic efficacy mainly shown in animal infection models | |||
| 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] | |
| Aminoglycosides | Cmax/MIC 8–10 [163] | High dose extended-dosing: troughs undetectable or <1 mcg/mL | ||
| Daptomycin | Cmax/MIC 59–94 [152] |
Abbreviations: fT>MIC percentage/fraction of dosing interval during which unbound antibiotic concentration remain above the MIC of targeted bacteria, AUC 0–24 /MIC ratio of the area under the concentration–time curve (AUC) of the unbound drug from 0–24 hour and the MIC of targeted bacteria, Peak (C max )/MIC ratio of the peak concentration during a dosing interval and the MIC of targeted bacteria.