Elucidating the pharmacokinetics/pharmacodynamics of aerosolized colistin against multidrug-resistant acinetobacter baumannii and klebsiella pneumoniae in a mouse lung infection model

Yu-Wei Lin, Qi Tony Zhou, Mei-Ling Han, Ke Chen, Nikolas J. Onufrak, Jiping Wang, John D. Turnidge, Benjamin P. Howden, Alan Forrest, Hak Kim Chan, Jian Li

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The pharmacokinetics/pharmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC) in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin.

Original languageEnglish
Article numbere01790
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume62
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • Acinetobacter baumannii
  • Gram-negative bacteria
  • Klebsiella pneumoniae
  • Polymyxin
  • Pulmonary administration
  • Respiratory tract infections

Cite this

@article{e94236fb3e6b447ab5dcc1292ded8423,
title = "Elucidating the pharmacokinetics/pharmacodynamics of aerosolized colistin against multidrug-resistant acinetobacter baumannii and klebsiella pneumoniae in a mouse lung infection model",
abstract = "The pharmacokinetics/pharmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC) in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin.",
keywords = "Acinetobacter baumannii, Gram-negative bacteria, Klebsiella pneumoniae, Polymyxin, Pulmonary administration, Respiratory tract infections",
author = "Yu-Wei Lin and Zhou, {Qi Tony} and Mei-Ling Han and Ke Chen and Onufrak, {Nikolas J.} and Jiping Wang and Turnidge, {John D.} and Howden, {Benjamin P.} and Alan Forrest and Chan, {Hak Kim} and Jian Li",
year = "2018",
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day = "1",
doi = "10.1128/AAC.01790-17",
language = "English",
volume = "62",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "1098-6596",
publisher = "American Society for Microbiology",
number = "2",

}

Elucidating the pharmacokinetics/pharmacodynamics of aerosolized colistin against multidrug-resistant acinetobacter baumannii and klebsiella pneumoniae in a mouse lung infection model. / Lin, Yu-Wei; Zhou, Qi Tony; Han, Mei-Ling; Chen, Ke; Onufrak, Nikolas J.; Wang, Jiping; Turnidge, John D.; Howden, Benjamin P.; Forrest, Alan; Chan, Hak Kim; Li, Jian.

In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 2, e01790, 01.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Elucidating the pharmacokinetics/pharmacodynamics of aerosolized colistin against multidrug-resistant acinetobacter baumannii and klebsiella pneumoniae in a mouse lung infection model

AU - Lin, Yu-Wei

AU - Zhou, Qi Tony

AU - Han, Mei-Ling

AU - Chen, Ke

AU - Onufrak, Nikolas J.

AU - Wang, Jiping

AU - Turnidge, John D.

AU - Howden, Benjamin P.

AU - Forrest, Alan

AU - Chan, Hak Kim

AU - Li, Jian

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AB - The pharmacokinetics/pharmacodynamics (PK/PD) of aerosolized colistin was investigated against Acinetobacter baumannii and Klebsiella pneumoniae over 24 h in a neutropenic mouse lung infection model. Dose fractionation studies were performed over 2.64 to 23.8 mg/kg/day, and the data were fitted to a sigmoid inhibitory model. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC) in the epithelial lining fluid was the most predictive PK/PD index for aerosolized colistin against both pathogens. Our study provides important pharmacological information for optimizing aerosolized colistin.

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KW - Gram-negative bacteria

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KW - Polymyxin

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