Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model

Cefquinome is a fourth-generation Cephalosporin approved for use in animals exclusively. The objective of this study was to explore the relationship of cefquinome pharmacokinetic/pharmacodynamic (PK/PD) indices with resistance selection of Staphylococcus aureus ATCC25923 in an in vitro model. Six do...

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Main Authors: Yafei eLi, Baoyi eFeng, Xiaoyan eGu, Dawei eYang, Zhenling eZeng, Bingxu eZhang, Huanzhong eDing
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-04-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00466/full
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author Yafei eLi
Baoyi eFeng
Xiaoyan eGu
Dawei eYang
Zhenling eZeng
Bingxu eZhang
Huanzhong eDing
author_facet Yafei eLi
Baoyi eFeng
Xiaoyan eGu
Dawei eYang
Zhenling eZeng
Bingxu eZhang
Huanzhong eDing
author_sort Yafei eLi
collection DOAJ
description Cefquinome is a fourth-generation Cephalosporin approved for use in animals exclusively. The objective of this study was to explore the relationship of cefquinome pharmacokinetic/pharmacodynamic (PK/PD) indices with resistance selection of Staphylococcus aureus ATCC25923 in an in vitro model. Six dosing regiments of cefquinome at an interval of 24 h for three consecutive times were simulated, resulting in maximum concentrations (Cmax) from 1/2 MIC to 16 MIC and half-lives (t1/2β) of 3 and 6 h, respectively. The in vitro sensitivity of S. aureus was monitored by bacterial susceptibility and dynamic time-kill curve experiments over the six cefquinome concentrations. The correlation between changes in bacterial susceptibility (MIC72/MIC0) and the percentage of time within mutant selection window (MSW) versus dosing interval (TMSW %) was subjected to Gaussian function and regression analysis. The results favored the consensus that time above MIC (T>MIC) was recognized as an important PK/PD parameter of cephalosporins for antibacterial efficiency. Cefquinome reached the maximum killing effect when T>MIC% attained approximately 40%~60%. The subsequent correlation analysis demonstrated that resistant S. aureus ATCC25923 was easy to occur when TMSW% attained an index of about 20% with t1/2β of 3 h after multiple dosing, and 40% with t1/2β of 6 h after multiple dosing.
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spelling doaj.art-42f793deecf64e7fa6589e55fd50938b2022-12-21T19:24:41ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-04-01710.3389/fmicb.2016.00466166929Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro ModelYafei eLi0Baoyi eFeng1Xiaoyan eGu2Dawei eYang3Zhenling eZeng4Bingxu eZhang5Huanzhong eDing6Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural UniversityLaboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural UniversityCentre for Veterinary Drug Residues,College of Veterinary Medicine,South China Agricultural UniversityChina Institute of Veterinary Drug ControlLaboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural UniversityLaboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural UniversityLaboratory of Veterinary Pharmacology, College of Veterinary Medicine, South China Agricultural UniversityCefquinome is a fourth-generation Cephalosporin approved for use in animals exclusively. The objective of this study was to explore the relationship of cefquinome pharmacokinetic/pharmacodynamic (PK/PD) indices with resistance selection of Staphylococcus aureus ATCC25923 in an in vitro model. Six dosing regiments of cefquinome at an interval of 24 h for three consecutive times were simulated, resulting in maximum concentrations (Cmax) from 1/2 MIC to 16 MIC and half-lives (t1/2β) of 3 and 6 h, respectively. The in vitro sensitivity of S. aureus was monitored by bacterial susceptibility and dynamic time-kill curve experiments over the six cefquinome concentrations. The correlation between changes in bacterial susceptibility (MIC72/MIC0) and the percentage of time within mutant selection window (MSW) versus dosing interval (TMSW %) was subjected to Gaussian function and regression analysis. The results favored the consensus that time above MIC (T>MIC) was recognized as an important PK/PD parameter of cephalosporins for antibacterial efficiency. Cefquinome reached the maximum killing effect when T>MIC% attained approximately 40%~60%. The subsequent correlation analysis demonstrated that resistant S. aureus ATCC25923 was easy to occur when TMSW% attained an index of about 20% with t1/2β of 3 h after multiple dosing, and 40% with t1/2β of 6 h after multiple dosing.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00466/fullStaphylococcus aureusin vitro modelMPCPK/PDCefquinome
spellingShingle Yafei eLi
Baoyi eFeng
Xiaoyan eGu
Dawei eYang
Zhenling eZeng
Bingxu eZhang
Huanzhong eDing
Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model
Frontiers in Microbiology
Staphylococcus aureus
in vitro model
MPC
PK/PD
Cefquinome
title Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model
title_full Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model
title_fullStr Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model
title_full_unstemmed Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model
title_short Correlation of PK/PD Indices with Resistance Selection for Cefquinome against Staphylococcus aureus in an in vitro Model
title_sort correlation of pk pd indices with resistance selection for cefquinome against staphylococcus aureus in an in vitro model
topic Staphylococcus aureus
in vitro model
MPC
PK/PD
Cefquinome
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00466/full
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