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Evidence for Establishing the Clinical Breakpoint of Cefquinome against Haemophilus Parasuis in China.

ABSTRACT: Haemophilus parasuis can cause high morbidity and mortality in swine. Cefquinome possesses excellent antibacterial activity against pathogens causing diseases of the respiratory tract. This study aimed to establish the clinical breakpoint (CBP) of cefquinome against H. parasuis and to monitor the resistance change. Referring to the minimum inhibitory concentration (MIC) distribution of cefquinome against 131 H. parasuis isolates, the MIC₅₀ and MIC₉₀ were determined to be 0.125 and 1 ?g/mL, respectively. And the epidemiological cutoff (ECOFF) value was 1 ?g/mL. HPS42 was selected as a representative strain for the pharmacodynamic (PD) experiment, pharmacokinetic (PK) experiment and clinical experiments. The PK/PD index values, area under concentration-time curve (AUC)/MIC, of the bacteriostatic, bactericidal, and bacterial elimination effects were 23, 41, and 51 h, respectively. The PK/PD cutoff was calculated as 0.125 ?g/mL by Monte Carlo simulation (MCS), and the clinical cutoff was 0.25-4 ?g/mL by WindoW. Combing these three values, the CBP of cefquinome against H. parasuis was found to be 1 ?g/mL. In conclusion, this was the first study to integrate various cutoffs to establish the CBP in the laboratory. It is helpful to distinguish wild type H. parasuis and reduce the probability of treatment failure.

SUBMITTER: Mi K

PROVIDER: S-EPMC7912692 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Evidence for Establishing the Clinical Breakpoint of Cefquinome against Haemophilus Parasuis in China.

Mi Kun K Sun Da D Li Mei M Hao Haihong H Zhou Kaixiang K Liu Zhenli Z Yuan Zonghui Z Huang Lingli L

Pathogens (Basel, Switzerland) 20210122 2

Haemophilus parasuis can cause high morbidity and mortality in swine. Cefquinome possesses excellent antibacterial activity against pathogens causing diseases of the respiratory tract. This study aimed to establish the clinical breakpoint (CBP) of cefquinome against H. parasuis and to monitor the resistance change. Referring to the minimum inhibitory concentration (MIC) distribution of cefquinome against 131 H. parasuis isolates, the MIC50 and MIC90 wer ...[more]

PMID: 33498972

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Project description:Background: In order to establish the clinical breakpoint (CBP) of danofloxacin against G. parasuis, three cutoff values, including epidemiological cutoff value (ECV), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (COPD) and clinical cutoff value (COCL), were obtained in the present study. Methods: The ECV was calculated using ECOFFinder base on the MIC distribution of danfloxacin against 347 G. parasuis collected from disease pigs. The COPD was established based on in vivo and ex vivo PK-PD modeling of danofloxacin both in plasma and pulmonary epithelial lining fluid (PELF) using Hill formula and Monte Carlo analysis. The COCL was established based on the relationship between the possibility of cure (POC) and MIC in the clinical trials using the "WindoW" approach, nonlinear regression and CART analysis. Results: The MIC50 and MIC90 of danofloxacin against 347 G. parasuis were 2 μg/mL and 8 μg/mL, respectively. The ECV value was set to 8 μg/mL using ECOFFinder. Concentration-time curves of danofloxacin were fitted with a two-compartment PK model. The PK parameters of the maximum concentration (Cmax) and area under concentration-time curves (AUC) in PELF were 3.67 ± 0.25 μg/mL and 24.28 ± 2.70 h·μg/mL, higher than those in plasma (0.67 ± 0.01 μg/mL and 4.47 ± 0.51 h·μg/mL). The peak time (Tmax) in plasma was 0.23 ± 0.07 h, shorter than that in PELF (1.61 ± 0.15 h). The COPD in plasma and PELF were 0.125 μg/mL and 0.5 μg/mL, respectively. The COCL calculated by WindoW approach, nonlinear regression and CART analysis were 0.125-4 μg/mL, 0.428 μg/mL and 0.56 μg/mL, respectively. The 0.5 μg/mL was selected as eligible COCL. The ECV is much higher than the COPD and COCL, and the clinical breakpoint based on data in plasma was largely different from that of PELF. Conclusions: Our study firstly established three cutoff values of danofloxacin against G. parasuis. It suggested that non-wild-type danofloxacin-resistant G. parasuis may lead to ineffective treatment by danofloxacin.

Dataset Information

Evidence for Establishing the Clinical Breakpoint of Cefquinome against Haemophilus Parasuis in China.

Publications

Evidence for Establishing the Clinical Breakpoint of Cefquinome against Haemophilus Parasuis in China.

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