Defining the pharmacokinetic/pharmacodynamic index of piperacillin/tazobactam within a hollow-fibre infection model to determine target attainment in intensive care patients.
JAC Antimicrob Resist
; 6(2): dlae036, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38476774
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 andmethods:
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 2â log10â cfu reduction was associated with 77% fT>MIC. Piperacillin/tazobactam therapy was defined as clinically 'ineffective' in â¼78% (7/9) patients. Around seventy-one percent (5/7) of these patients had a probability of >10% that 2â log10â 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 2â log10 kill. Doses to achieve this target should be considered when treating patients in ICU.
Texto completo:
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Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
JAC Antimicrob Resist
Año:
2024
Tipo del documento:
Article