Population Pharmacokinetics and Pharmacodynamics of Extended-Infusion Piperacillin and Tazobactam in Critically Ill Children

被引:44
|
作者
Nichols, Kristen [1 ,2 ]
Chung, Eun Kyoung [3 ,4 ,6 ]
Knoderer, Chad A. [1 ]
Buenger, Lauren E. [2 ]
Healy, Daniel P. [5 ]
Dees, Jennifer [5 ]
Crumby, Ashley S. [2 ,3 ,4 ,7 ]
Kays, Michael B. [3 ,4 ]
机构
[1] Butler Univ, Coll Pharm & Hlth Sci, Indianapolis, IN 46208 USA
[2] Indiana Univ Hlth, Riley Hosp Children, Indianapolis, IN USA
[3] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA
[4] Purdue Univ, Coll Pharm, Indianapolis, IN USA
[5] Univ Cincinnati, James L Winkle Coll Pharm, Cincinnati, OH USA
[6] Kyung Hee Univ, Coll Pharm, Dept Pharm, Seoul, South Korea
[7] Univ Mississippi, University, MS 38677 USA
关键词
STEADY-STATE PHARMACOKINETICS; BETA-LACTAM ANTIBIOTICS; PROLONGED INFUSION; CYSTIC-FIBROSIS; DOSING STRATEGY; INFANTS; IMPLEMENTATION; NEUTROPENIA; COMBINATION; INFECTIONS;
D O I
10.1128/AAC.02089-15
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin-tazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) for a cumulative percentage of the dosing interval that the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (T-MIC) of >= 50% was calculated at MICs ranging from 0.25 to 64 mg/liter. The mean +/- standard deviation (SD) age, weight, and estimated glomerular filtration rate were 5 +/- 3 years, 17 +/- 6.2 kg, and 118 +/- 41 ml/min/1.73m(2), respectively. A one-compartment model with zero-order input and first-order elimination best fit the pharmacokinetic data for both drugs. Weight was significantly associated with piperacillin clearance, and weight and sex were significantly associated with tazobactam clearance. Pharmacokinetic parameters (mean +/- SD) for piperacillin and tazobactam were as follows: clearance, 0.22 +/- 0.07 and 0.19 +/- 0.07 liter/h/kg, respectively; volume of distribution, 0.43 +/- 0.16 and 0.37 +/- 0.14 liter/kg, respectively. All extended-infusion regimens achieved PTAs of >90% at MICs of <= 16 mg/liter. Only the 3-h infusion regimens given every 6 h achieved PTAs of >90% at an MIC of 32 mg/liter. For susceptible bacterial pathogens, piperacillin-tazobactam doses of >= 80/10 mg/kg given every 8 h and infused over 4 h achieve adequate pharmacodynamic exposures in critically ill children.
引用
收藏
页码:522 / 531
页数:10
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