open access

Vol 48, No 1 (2016)
Original and clinical articles
Published online: 2015-11-20
Submitted: 2015-08-24
Accepted: 2015-11-09
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A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam

Jiřina Martínková, Manu L.N.G. Malbrain, Eduard Havel, Petr Šafránek, Jan Bezouška, Milan Kaška
DOI: 10.5603/AIT.a2015.0082
·
Anaesthesiol Intensive Ther 2016;48(1):23-28.

open access

Vol 48, No 1 (2016)
Original and clinical articles
Published online: 2015-11-20
Submitted: 2015-08-24
Accepted: 2015-11-09

Abstract

Background: In critically ill patients, multi-trauma and intensive therapy can influence the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics with time-dependent bacterial killing. Consequently, PK/PD targets (%fT>MIC) — crucial for antimicrobial effects -may not be attained.

Methods: Two patients admitted to the surgical ICU of the University Hospital in Hradec Králove for multiple-trauma were given piperacillin/tazobactam by 1-hour IV infusion 4/0.5 g every 8h. PK variables: total and renal clearance (CLtot, CLR), volume of distribution (Vd), and elimination half-life (T1/2) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output). The PK/PD target attainment (100%fT>MIC) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT>MIC) within days 4-8 (when CFB culminates and disappears). Piperacillin concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and corrected for unbound fraction (22%).

Results: CFB culminated over days 2−5 reaching 15−30 L and was associated with a large Vd (29−42 L). While MDRD in patient 1 was low (0.3−0.4 mL s-1 1.7 m-2), that of patient 2 was increasing (> 3.1 mL s-1 1.7 m-2), which was associated with augmented CLR. In patient 2, the fT reached only 62, 52, and 44% on days 4, 6, and 8, respectively. In patient 1, the %fT was much higher, attaining values four to fivefold greater than that targeted.

Conclusions: Critically ill patients are at risk of drug under- or overdosing without dose up-titration with regard to covariate effects and individual drug pharmacokinetics.

Abstract

Background: In critically ill patients, multi-trauma and intensive therapy can influence the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics with time-dependent bacterial killing. Consequently, PK/PD targets (%fT>MIC) — crucial for antimicrobial effects -may not be attained.

Methods: Two patients admitted to the surgical ICU of the University Hospital in Hradec Králove for multiple-trauma were given piperacillin/tazobactam by 1-hour IV infusion 4/0.5 g every 8h. PK variables: total and renal clearance (CLtot, CLR), volume of distribution (Vd), and elimination half-life (T1/2) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output). The PK/PD target attainment (100%fT>MIC) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT>MIC) within days 4-8 (when CFB culminates and disappears). Piperacillin concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and corrected for unbound fraction (22%).

Results: CFB culminated over days 2−5 reaching 15−30 L and was associated with a large Vd (29−42 L). While MDRD in patient 1 was low (0.3−0.4 mL s-1 1.7 m-2), that of patient 2 was increasing (> 3.1 mL s-1 1.7 m-2), which was associated with augmented CLR. In patient 2, the fT reached only 62, 52, and 44% on days 4, 6, and 8, respectively. In patient 1, the %fT was much higher, attaining values four to fivefold greater than that targeted.

Conclusions: Critically ill patients are at risk of drug under- or overdosing without dose up-titration with regard to covariate effects and individual drug pharmacokinetics.

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Keywords

PK/PD target attainment, body fluid retention, pharmacokinetics, pharmacodynamics, piperacillin, critically ill patients, personalised therapy

About this article
Title

A pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam

Journal

Anaesthesiology Intensive Therapy

Issue

Vol 48, No 1 (2016)

Pages

23-28

Published online

2015-11-20

DOI

10.5603/AIT.a2015.0082

Bibliographic record

Anaesthesiol Intensive Ther 2016;48(1):23-28.

Keywords

PK/PD target attainment
body fluid retention
pharmacokinetics
pharmacodynamics
piperacillin
critically ill patients
personalised therapy

Authors

Jiřina Martínková
Manu L.N.G. Malbrain
Eduard Havel
Petr Šafránek
Jan Bezouška
Milan Kaška

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