Model-informed dose optimization for prophylactic piperacillin-tazobactam in perioperative pediatric critically ill patients.

IF 4.1 2区 医学 Q2 MICROBIOLOGY
Antimicrobial Agents and Chemotherapy Pub Date : 2025-03-05 Epub Date: 2025-02-06 DOI:10.1128/aac.01227-24
Wen Rui Tan, Kei Irie, Carter McIntire, Julie Luna Torres, Rhonda Jones, Abigayle Gibson, Tomoyuki Mizuno, Sonya Tang Girdwood
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引用次数: 0

Abstract

Piperacillin/tazobactam (PTZ) is frequently prescribed during the perioperative period as prophylaxis in critically ill patients. Current international guidelines recommend that the pediatric intraoperative dosing regimen for PTZ be 90-112.5 mg/kg (80-100 mg/kg as piperacillin [PIP]) administered every 2 hours (Q2H). Concerns have been raised not only about the risk of nephrotoxicity due to elevated PIP exposure but also regarding the practicality of adhering to a 2-h dosing interval in clinical settings. To address these concerns, we employed population pharmacokinetic (PK) modeling and simulation approaches to optimize PTZ dosing regimens in pediatric intraoperative patients. PIP plasma concentration data were obtained from 34 patients using an opportunistic sampling strategy. A two-compartment model was found to adequately describe the PK data. Creatinine clearance was identified as a significant covariate on clearance. The inclusion of inter-occasion variability significantly improved model fit. Simulations across body weights of 10-70 kg and creatinine clearance of 20-130 mL/min/1.73 m2 demonstrated that 6-15 mg/kg Q2H, or a 10 mg/kg loading dose followed by 1.0-2.75 mg/kg/h continuous infusion would achieve free PIP concentrations being above the minimum inhibitory concentration (MIC) for 100% of the dosing interval (100% fT >1× MIC). For achieving 100% fT >4× MIC, 25-55 mg/kg Q2H or a 20 mg/kg loading dose followed by 3.25-9.25 mg/kg/h continuous infusion was derived. The model-informed simulations indicated that both lower Q2H doses and continuous infusion methods are clinically viable options and potentially resolve current clinical challenges during intraoperative dosing.

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来源期刊
CiteScore
10.00
自引率
8.20%
发文量
762
审稿时长
3 months
期刊介绍: Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.
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