Dataset Information

Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

ABSTRACT:

Background

It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%-100% fT_>1-4×MIC). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes.

Objectives

The first aim of this study was to define the optimal PK/PD index of piperacillin/tazobactam with a hollow-fibre infection model (HFIM). The second aim was to predict whether these PK/PD targets are currently achieved in critically ill patients through PK/PD model simulation.

Patients and methods

A dose-fractionation study comprising 21 HFIM experiments was performed against a range of Gram-negative bacterial pathogens, doses and infusion times. Clinical data and dose histories from a case series of nine patients with a known bacterial infection treated with piperacillin/tazobactam in the ICU were collected. The PK/PD index and predicted plasma concentrations and therefore target attainment of the patients were simulated using R version 4.2.1.

Results

fT _>MIC was found to be the best-fitting PK/PD index for piperacillin/tazobactam. Bactericidal activity with 2 log₁₀ cfu reduction was associated with 77% fT_>MIC. Piperacillin/tazobactam therapy was defined as clinically 'ineffective' in ∼78% (7/9) patients. Around seventy-one percent (5/7) of these patients had a probability of >10% that 2 log₁₀ cfu reduction was not attained.

Conclusions

Our dose-fractionation study indicates an optimal PK/PD target in piperacillin/tazobactam therapies should be 77% fT_>MIC for 2 log₁₀ kill. Doses to achieve this target should be considered when treating patients in ICU.

SUBMITTER: Wenker SAM

PROVIDER: S-EPMC10928666 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Publications

Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

Wenker Suzanne A M SAM Alabdulkarim Najla N Readman John B JB Slob Elise M A EMA Satta Giovanni G Ali Shanom S Gadher Nishma N Shulman Rob R Standing Joseph F JF

JAC-antimicrobial resistance 20240312 2

<h4>Background</h4>It is important to optimize dosing schemes of antibiotics to maximize the probability of therapeutic success. The recommended pharmacokinetic/pharmacodynamic (PK/PD) index for piperacillin/tazobactam therapy in clinical studies ranges widely (50%-100% <i>fT</i><sub>>1-4×MIC</sub>). Dosing schemes failing to achieve PK/PD targets may lead to negative treatment outcomes.<h4>Objectives</h4>The first aim of this study was to define the optimal PK/PD index of piperacillin/tazobacta ...[more]

PMID: 38476774

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Dataset Information

Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

Background

Objectives

Patients and methods

Results

Conclusions

Publications

Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.

Similar Datasets

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