產食動物抗生素抗藥性：法國、日本及台灣之防疫一體分析

Abstract

抗生素抗藥性（AMR）為影響防疫一體（One Health）架構之重要議題。本報告視產食動物之抗生素使用為人為因素，以全面的觀點探討其傳播抗生素抗藥性之可能性。研究方法包括分析法國、日本及台灣之產食動物抗生素使用習慣及實地樣本之抗藥性分析。結果顯示相較於日本及台灣，法國具有較強力度之法規及較少之抗生素使用。相似趨勢亦發現於廢水宏基因體定序分析，與日本及台灣之集群相比，法國樣本之集群表現出較為獨立之趨勢。依據前述之研究結果，同時擁有β-內醯胺類抗生素及多黏菌素抗性之抗藥性基因被提議作為追溯產食動物抗藥性來源之指標基因。抗生素敏感性試驗更進一步的被用於探討產食動物相關樣品分離出之菌株抗藥性機制。自法國肉牛農場採集之動物及環境樣本篩選分離出之革蘭氏陰性菌菌株用於探討以質體為媒介之抗藥性傳播，而自日本蔬菜農場採集之含產食動物糞便肥料樣本篩選分離出之革蘭氏陽性菌菌株則被用於探討其可能之β-內醯胺類抗生素抗藥性。ESKAPEE病原體所屬之菌屬在抗藥性傳播中可能扮演的生態棲位也同時於本研究中探討。產食動物抗生素使用及抗生素抗藥性之間存在由多樣因子構成之關聯，現今之相關研究因而有所侷限，多元之研究方法因此被建議使用以彌補研究之不足。本報告提議以功能性宏基因體定序分析作為填補現今產食動物抗生素抗藥性研究缺口之方法，從而連接防疫一體及全球意識，提升抗生素抗藥性監測效能。整體而言，本研究提供關於產食動物抗生素抗藥性的全面見解，旨在守護所有生物與環境的健康與福祉，並為未來抗生素抗藥性提供可能之研究方向。

Antimicrobial resistance (AMR) is a serious concern that affects the One Health sectors. This report examines antibiotic use in food-producing animals as an anthropogenic factor, identifying its potential contribution to resistance spread by analyzing antibiotic use patterns and real-life sample resistance profiling in France, Japan, and Taiwan to provide a comprehensive perspective. The results indicated stricter policies and lower levels of antibiotic use in France compared to Japan and Taiwan. Similar trends were discovered in the wastewater metagenomic analyses, with samples from France forming more distinct clusters than the other two countries. Genes resistant to both beta-lactam and polymyxin are proposed as potential markers to track animal-originated sources. Phenotypic profiling was further performed to explore strain-specific, animal-originated resistance mechanisms by identifying plasmid-mediated resistance in Gram-negative isolates from France and possible beta-lactam resistance in Gram-positive isolates from Japan, alongside the consideration of possible ecological roles played by ESKAPEE-associated genera in resistance dissemination. The relationship between food-producing animal antibiotic practices and AMR is shaped by complex factors, which pose limitations for current studies. A multi-method approach is therefore recommended to complement existing constraints. Functional metagenomics is proposed as a potential solution to address current gaps in food-producing animals’ AMR research to bridge One Health and global efforts toward improved AMR surveillance. Overall, this study provides insights about AMR related to food-producing animals with the aim of protecting the health and welfare of all living beings, and offers possible directions for future AMR research.