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

BMC Infectious Diseases

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	AUC_0–24/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
		Vancomycin	b) trough concentrations >10 mg/L to avoid development of resistance [16]	Trough concentrations >27 mg/L with intermittent dosing
		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 (C_max)/MIC	Fluoroquinolones	C_max/MIC >10 prevent emergent of resistant mutants in in vivo and in vitro models [137, 161, 162]
		Aminoglycosides	C_max/MIC 8–10 [163]	High dose extended-dosing: troughs undetectable or <1 mcg/mL
		Daptomycin	C_max/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.

ISSN: 1471-2334