Prudent Use of Tylosin for Treatment of Mycoplasma gallisepticum Based on Its Clinical Breakpoint and Lung Microbiota Shift

Anxiong Huang; Shuge Wang; Jinli Guo; Yufeng Gu; Jun Li; Lingli Huang; Xu Wang; Yanfei Tao; Zhenli Liu; Zonghui Yuan; Haihong Hao

doi:10.3389/fmicb.2021.712473

Prudent Use of Tylosin for Treatment of Mycoplasma gallisepticum Based on Its Clinical Breakpoint and Lung Microbiota Shift

Front Microbiol. 2021 Sep 9:12:712473. doi: 10.3389/fmicb.2021.712473. eCollection 2021.

Authors

Anxiong Huang^{1

2}, Shuge Wang³, Jinli Guo^{1

2}, Yufeng Gu^{1

2}, Jun Li⁴, Lingli Huang^{1

2}, Xu Wang^{1

2}, Yanfei Tao^{1

2}, Zhenli Liu^{1

2}, Zonghui Yuan^{1

2}, Haihong Hao^{1

2}

Affiliations

¹ National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, China.
² MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, China.
³ National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, China.
⁴ Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing, China.

Abstract

The aim of this study was to explore the prudent use of tylosin for the treatment of chronic respiratory infectious diseases in chickens caused by Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and its effect on lung microbiota. The CBP was established based on the wild-type/epidemiological cutoff value (CO_WT/ECV), pharmacokinetics-pharmacodynamics (PK-PD) cutoff value (CO_PD), and clinical cutoff value (CO_CL) of tylosin against MG. The minimum inhibitory concentration (MIC) of tylosin against 111 MG isolates was analyzed and the CO_WT was 2 μg/ml. M17 with MIC of 2 μg/ml was selected as a representative strain for the PK-PD study. The CO_PD of tylosin against MG was 1 μg/ml. The dosage regimen formulated by the PK-PD study was 3 days administration of tylosin at a dose of 45.88 mg/kg b.w. with a 24-h interval. Five different MIC MGs were selected for clinical trial, and the CO_CL of tylosin against MG was 0.5 μg/ml. According to the CLSI decision tree, the CBP of tylosin against MG was set up as 2 μg/ml. The effect of tylosin on lung microbiota of MG-infected chickens was analyzed by 16S rRNA gene sequencing. Significant change of the lung microbiota was observed in the infection group and treatment group based on the principal coordinate analysis and the Venn diagrams of the core and unique OTU. The phyla Firmicutes and Proteobacteria showed difference after MG infection and treatment. This study established the CBP of tylosin against MG. It also provided scientific data for the prudent use of tylosin based on the evaluation of MG infection and tylosin treatment on the lung microbiota.

Keywords: Mycoplasma gallisepticum; clinical breakpoint; dosage regimen; lung microbiota; tylosin.