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Table 3 Summary of concentration-dependent with time-dependence and concentration-dependent antibiotics, and proposed targets for TDM dose adjustments

From: How do we use therapeutic drug monitoring to improve outcomes from severe infections in critically ill patients?

  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]  
  1. 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.