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In vivo activity of cefquinome against Escherichia coli in the thighs of neutropenic mice

文献类型： 外文期刊

作者： Shan, Qi 1 ; Liang, Chaoping 1 ; Wang, Jing 1 ; Li, Jufeng 3 ; Zeng, Zhenling 1 ;

作者机构： 1.South China Agr Univ, Coll Vet Med, Natl Reference Lab Vet Drug Residues SCAU, Guangzhou, Guangdong, Peoples R China

2.Chinese Acad Fishery Sci, Pearl River Fisheries Res Inst, Minist Agr, Key Lab Trop & Subtrop Fishery Resource Applicat, Guangzhou, Guangdong, Peoples R China

3.Jinan Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China

期刊名称：ANTIMICROBIAL AGENTS AND CHEMOTHERAPY （ 影响因子：5.191； 五年影响因子：5.346 ）

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收录情况： SCI

摘要： Cefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against enteric Gram-negative bacilli such as Escherichia coli. We utilized a neutropenic mouse model of colibacillosis to examine the pharmacodynamic (PD) characteristics of cefquinome, as measured by organism number in homogenized thigh cultures after 24 h of therapy. Serum drug levels following 4-fold-escalating single doses of cefquinome were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic (PK) properties of cefquinome were linear over a dose range of 10 to 640 mg/kg of body weight. Serum half-lives ranged from 0.29 to 0.32 h. Dose fractionation studies over a 24-h dose range of 2.5 to 320 mg/kg were conducted every 3, 6,12, or 24 h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. The free percentage of the dosing interval that the serum levels exceed the MIC (fT>MIC) was the PK-PD index that best correlated with efficacy (R2= 73% for E. coli, compared with 13% for the maximum concentration of the free drug in serum [fcmax]/MIC and 45% for the free-drug area under the concentration-time curve from 0 to 24 h |/AUC0-24]/ MIC). Subsequently, we employed a similar dosing strategy by using 4-fold-increasing total cefquinome doses administered every 4 h to treat animals infected with four additional E. coli isolates. A sigmoid maximum-effect (Emax) model was used to estimate the magnitudes of the % T >MICassociated with net bacterial stasis, a 1 -log10CFU reduction from baseline, and a 2-log10CPU reduction from baseline; the corresponding values were 28.01% ?2.27%, 37.23% ?4.05%, and 51.69% ?9.72%. The potent bactericidal activity makes cefquinome an attractive option for the treatment of infections caused by E. coli.

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