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. 2021 Jan 22;10(2):105.
doi: 10.3390/pathogens10020105.

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

Kun Mi  1 , Da Sun  1 , Mei Li  2 , Haihong Hao  1   2 , Kaixiang Zhou  2 , Zhenli Liu  1   2 , Zonghui Yuan  1   2   3 , Lingli Huang  1   2   3
Affiliations

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

Kun Mi et al. Pathogens. .

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 μg/mL, respectively. And the epidemiological cutoff (ECOFF) value was 1 μg/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 μg/mL by Monte Carlo simulation (MCS), and the clinical cutoff was 0.25-4 μg/mL by WindoW. Combing these three values, the CBP of cefquinome against H. parasuis was found to be 1 μg/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.

Keywords: Haemophilus parasuis; PK/PD cutoff; cefquinome; clinical breakpoint; clinical cutoff; epidemiological cutoff.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Distribution of Minimum Inhibitory Concentration (MIC) of cefquinome against H. parasuis. (A) The number of strains is 131; (B) combined with Xiao’s result [12], the number of strains is 344.
Figure 2
Figure 2
The in vitro time–killing curve of cefquinome against HPS42.
Figure 3
Figure 3
The ex vivo time–killing curves in serum. (A) Represented curves in healthy group and (B) Represented curves in diseased group. Note: Bacterial number was determined at different time points by a variety of serum samples from the pharmacokinetic (PK) study. Legends represents the cefquinome concentration in the sampling time point.
Figure 3
Figure 3
The ex vivo time–killing curves in serum. (A) Represented curves in healthy group and (B) Represented curves in diseased group. Note: Bacterial number was determined at different time points by a variety of serum samples from the pharmacokinetic (PK) study. Legends represents the cefquinome concentration in the sampling time point.
Figure 4
Figure 4
The concentration–time curves of cefquinome in serum from the healthy pigs (n = 6) and the diseased pigs (n = 6) after I.M. administration 2mg/kg bodyweight (b.w.).
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