Pharmacokinetic/pharmacodynamic modeling to predict in vivo effectiveness of various dosing regimens of piperacillin/tazobactam and piperacillin monotherapy against gram-negative pulmonary isolates from patients managed in intensive care units in 2002

Chris Frei, David S. Burgess

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Original languageEnglish
Pages (from-to)2335-2341
Number of pages7
JournalClinical Therapeutics
Volume30
Issue number12
DOIs
StatePublished - Dec 2008

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Piperacillin
Intensive Care Units
Pharmacokinetics
Enterobacteriaceae
Lung
Acinetobacter baumannii
Sample Size
Pseudomonas aeruginosa
Healthy Volunteers
tazobactam drug combination piperacillin
Serum

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{e592f5c7495b4c4abb6d2f2c27727d89,
title = "Pharmacokinetic/pharmacodynamic modeling to predict in vivo effectiveness of various dosing regimens of piperacillin/tazobactam and piperacillin monotherapy against gram-negative pulmonary isolates from patients managed in intensive care units in 2002",
abstract = "Objective: This study compared the pharmacokinetic/pharmacodynamic (PK/PD) properties of piperacillin/tazobactam (PTZ) combination treatment with those of piperacillin (PIP) monotherapy against clinical gram-negative pulmonary isolates from US patients treated in intensive care units. Methods: Computer modeling was used to integrate national in vitro microbiologic data from 2002 with pharmacokinetic data from published studies in healthy volunteers. PTZ (3.375 g q4h, 3.375 g q6h, 4.5 g q6h, and 4.5 g q8h) and PIP (3 g q4h, 3 g q6h, 4 g q6h, and 4 g q8h) were modeled using Monte Carlo simulations. The cumulative fraction of response (CFR) was determined for percentage of time that the free serum concentration remained above the MIC of ≥30{\%} (bacteriostatic) and ≥50{\%} (bactericidal). Because simulated comparisons with an artificially derived sample size were used, statistical methods were not applied. Results: Overall, 2584 gram-negative pulmonary isolates were evaluated, including Enterobacteriaceae (n = 1430), Pseudomonas aeruginosa (n = 799), Acinetobacter baumannii (n = 179), and {"}other{"} (n = 176). The percents susceptible with PTZ and PIP were as follows: Enterobacteriaceae, 86{\%} and 66{\%}, respectively; P aeruginosa, 89{\%} and 84{\%}; and A baumannii, 47{\%} and 34{\%}. CFR rates with PTZ were numerically higher than those with PIP against Enterobacteriaceae (ranges, 86{\%}-89{\%} and 66{\%}-73{\%}, respectively) and A baumannii (47{\%}-53{\%} and 33{\%}-42{\%}), but not against P aeruginosa (79{\%}-84{\%} and 75{\%}-81{\%}). Conclusion: Results from PK/PD models with Monte Carlo simulation suggested that susceptibility differences among these selected gram-negative isolates collected in 2002 may be of sufficient magnitude to result in notable PK/PD differences between PTZ and PIP.",
keywords = "aerobic gram-negative bacteria, infectious disease, Monte Carlo simulation, piperacillin/tazobactam, pulmonary disease",
author = "Chris Frei and Burgess, {David S.}",
year = "2008",
month = "12",
doi = "10.1016/j.clinthera.2008.12.009",
language = "English",
volume = "30",
pages = "2335--2341",
journal = "Clinical Therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",
number = "12",

}

TY - JOUR

T1 - Pharmacokinetic/pharmacodynamic modeling to predict in vivo effectiveness of various dosing regimens of piperacillin/tazobactam and piperacillin monotherapy against gram-negative pulmonary isolates from patients managed in intensive care units in 2002

AU - Frei, Chris

AU - Burgess, David S.

PY - 2008/12

Y1 - 2008/12

N2 - Objective: This study compared the pharmacokinetic/pharmacodynamic (PK/PD) properties of piperacillin/tazobactam (PTZ) combination treatment with those of piperacillin (PIP) monotherapy against clinical gram-negative pulmonary isolates from US patients treated in intensive care units. Methods: Computer modeling was used to integrate national in vitro microbiologic data from 2002 with pharmacokinetic data from published studies in healthy volunteers. PTZ (3.375 g q4h, 3.375 g q6h, 4.5 g q6h, and 4.5 g q8h) and PIP (3 g q4h, 3 g q6h, 4 g q6h, and 4 g q8h) were modeled using Monte Carlo simulations. The cumulative fraction of response (CFR) was determined for percentage of time that the free serum concentration remained above the MIC of ≥30% (bacteriostatic) and ≥50% (bactericidal). Because simulated comparisons with an artificially derived sample size were used, statistical methods were not applied. Results: Overall, 2584 gram-negative pulmonary isolates were evaluated, including Enterobacteriaceae (n = 1430), Pseudomonas aeruginosa (n = 799), Acinetobacter baumannii (n = 179), and "other" (n = 176). The percents susceptible with PTZ and PIP were as follows: Enterobacteriaceae, 86% and 66%, respectively; P aeruginosa, 89% and 84%; and A baumannii, 47% and 34%. CFR rates with PTZ were numerically higher than those with PIP against Enterobacteriaceae (ranges, 86%-89% and 66%-73%, respectively) and A baumannii (47%-53% and 33%-42%), but not against P aeruginosa (79%-84% and 75%-81%). Conclusion: Results from PK/PD models with Monte Carlo simulation suggested that susceptibility differences among these selected gram-negative isolates collected in 2002 may be of sufficient magnitude to result in notable PK/PD differences between PTZ and PIP.

AB - Objective: This study compared the pharmacokinetic/pharmacodynamic (PK/PD) properties of piperacillin/tazobactam (PTZ) combination treatment with those of piperacillin (PIP) monotherapy against clinical gram-negative pulmonary isolates from US patients treated in intensive care units. Methods: Computer modeling was used to integrate national in vitro microbiologic data from 2002 with pharmacokinetic data from published studies in healthy volunteers. PTZ (3.375 g q4h, 3.375 g q6h, 4.5 g q6h, and 4.5 g q8h) and PIP (3 g q4h, 3 g q6h, 4 g q6h, and 4 g q8h) were modeled using Monte Carlo simulations. The cumulative fraction of response (CFR) was determined for percentage of time that the free serum concentration remained above the MIC of ≥30% (bacteriostatic) and ≥50% (bactericidal). Because simulated comparisons with an artificially derived sample size were used, statistical methods were not applied. Results: Overall, 2584 gram-negative pulmonary isolates were evaluated, including Enterobacteriaceae (n = 1430), Pseudomonas aeruginosa (n = 799), Acinetobacter baumannii (n = 179), and "other" (n = 176). The percents susceptible with PTZ and PIP were as follows: Enterobacteriaceae, 86% and 66%, respectively; P aeruginosa, 89% and 84%; and A baumannii, 47% and 34%. CFR rates with PTZ were numerically higher than those with PIP against Enterobacteriaceae (ranges, 86%-89% and 66%-73%, respectively) and A baumannii (47%-53% and 33%-42%), but not against P aeruginosa (79%-84% and 75%-81%). Conclusion: Results from PK/PD models with Monte Carlo simulation suggested that susceptibility differences among these selected gram-negative isolates collected in 2002 may be of sufficient magnitude to result in notable PK/PD differences between PTZ and PIP.

KW - aerobic gram-negative bacteria

KW - infectious disease

KW - Monte Carlo simulation

KW - piperacillin/tazobactam

KW - pulmonary disease

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U2 - 10.1016/j.clinthera.2008.12.009

DO - 10.1016/j.clinthera.2008.12.009

M3 - Article

C2 - 19167592

AN - SCOPUS:58249144763

VL - 30

SP - 2335

EP - 2341

JO - Clinical Therapeutics

JF - Clinical Therapeutics

SN - 0149-2918

IS - 12

ER -