Therapeutic drug monitoring of β-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures.

Autor:	Wong, Gloria, Lipman, Jeffrey, Briscoe, Scott, McWhinney, Brett, Ungerer, Jacobus, Ally, Mumtaz, Roberts, Jason A
Předmět:	DRUG monitoring BETA lactam antibiotics PATIENTS CEFTRIAXONE CEFAZOLIN MEROPENEM ANTIBIOTICS CATASTROPHIC illness COMPARATIVE studies LONGITUDINAL method RESEARCH methodology MEDICAL cooperation MICROBIAL sensitivity tests RESEARCH LOGISTIC regression analysis EVALUATION research TREATMENT effectiveness AMPICILLIN
Zdroj:	Journal of Antimicrobial Chemotherapy (JAC); Nov2018, Vol. 73 Issue 11, p3087-3094, 8p
Abstrakt:	Objectives: To describe the achievement of unbound β-lactam antibiotic concentration targets in a therapeutic drug monitoring (TDM) programme in critically ill patients, and the factors associated with failure to achieve a target concentration.Patients and methods: Plasma samples and clinical data were obtained for analysis from a single centre prospectively. Unbound concentrations of ceftriaxone, cefazolin, meropenem, ampicillin, benzylpenicillin, flucloxacillin and piperacillin were directly measured using ultracentrifugation. Factors associated with the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets or negative clinical outcomes were evaluated with binomial logistic regression.Results: TDM data from 330 patients, and 369 infection episodes, were included. The range of doses administered was 99.4% ± 45.1% relative to a standard daily dose. Dose increases were indicated in 33.1% and 63.4% of cases to achieve PK/PD targets of 100% fT>MIC and 100% fT>4×MIC, respectively. Dose reduction was indicated in 17.3% of cases for an upper PK/PD threshold of 100% fT>10×MIC. Higher protein bound β-lactams (ceftriaxone and benzylpenicillin) had better therapeutic target attainment (P < 0.01), but were prone to excessive dosing. Augmented renal clearance (calculated CLCR >130 mL/min) increased the odds of failure to achieve 100% fT>MIC and 100% fT>4×MIC (OR 2.47 and 3.05, respectively; P < 0.01).Conclusions: Measuring unbound concentrations of β-lactams as part of a routine TDM programme is feasible and demonstrates that a large number of critically ill patients do not achieve predefined PK/PD targets. The clinical significance of this finding is unknown due to the lack of correlation between PK/PD findings and clinical outcomes. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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