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. 2022 Mar 17;11(3):403.
doi: 10.3390/antibiotics11030403.

Rational Use of Danofloxacin for Treatment of Mycoplasma gallisepticum in Chickens Based on the Clinical Breakpoint and Lung Microbiota Shift

Shuge Wang  1   2   3 , Anxiong Huang  1   2 , Yufeng Gu  1   2 , Jun Li  4 , Lingli Huang  1   2 , Xu Wang  1   2 , Yanfei Tao  1   2 , Zhenli Liu  1   2 , Congming Wu  3 , Zonghui Yuan  1   2 , Haihong Hao  1   2
Affiliations

Rational Use of Danofloxacin for Treatment of Mycoplasma gallisepticum in Chickens Based on the Clinical Breakpoint and Lung Microbiota Shift

Shuge Wang et al. Antibiotics (Basel). .

Abstract

The study was to explore the rational use of danofloxacin against Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and the effect on lung microbiota. The CBP was established according to epidemiological cutoff value (ECV/COWT), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (COPD) and clinical cutoff value (COCL). The ECV was determined by the micro-broth dilution method and analyzed by ECOFFinder software. The COPD was determined according to PK-PD modeling of danofloxacin in infected lung tissue with Monte Carlo analysis. The COCL was performed based on the relationship between the minimum inhibitory concentration (MIC) and the possibility of cure (POC) from clinical trials. The CBP in infected lung tissue was 1 μg/mL according to CLSI M37-A3 decision tree. The 16S ribosomal RNA (rRNA) sequencing results showed that the lung microbiota, especially the phyla Firmicutes and Proteobacteria had changed significantly along with the process of cure regimen (the 24 h dosing interval of 16.60 mg/kg b.w for three consecutive days). Our study suggested that the rational use of danofloxacin for the treatment of MG infections should consider the MIC and effect of antibiotics on the respiratory microbiota.

Keywords: Mycoplasma gallisepticum; PK–PD cutoff values; clinical breakpoint; clinical cutoff values; danofloxacin; epidemiological cutoff values; lung microbiota.

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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
Nonlinear regression of MIC distribution of danofloxacin against MG (n = 111). Note: “Raw Count” was the measured MICs of danofloxacin; “Fitted” was the simulated MICs of danofloxacin.
Figure 2
Figure 2
The killing-time curves of danofloxacin against M19 in FM-4 broth (in vitro). Note: M19 is a highly pathogenic strain as determined by the chicken embryo virulence test. FM-4 is a medium for the culture of MG. MIC (2 μg/mL) is the minimum inhibitory concentration of danofloxacin against M19.
Figure 3
Figure 3
Ex vivo killing-time curves in infected lung tissue.
Figure 4
Figure 4
Mean concentration versus time for danofloxacin in healthy and diseased lung ((A): healthy lung (B): diseased lung).
Figure 5
Figure 5
Taxonomic classification of the 16S rRNA sequences at phylum. Note: HWK represents the control group; GW represents the infection group; ZW represents the treatment group, and ZHW represents the post-treatment group.
Figure 6
Figure 6
Venn diagrams of the common and unique OTUs of the four groups. Note: HWK represents the control group; GW represents the infection group; ZW represents the treatment group, and ZHW represents the post-treatment group. The numbers in the Venn diagram indicate the common (overlapping part) and unique OTUs of each sample group. The common OTUs represent the overlapping part between two or more groups, and the unique OTUs represent the part where no overlap occurred.
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