限制抗菌药物使用对降低耐药率作用的争议:解读与思考

Debate on impact of restriction on antimicrobial use on antimicrobial resistance rate:explanation and deliberation

抗菌药物耐药是广为关注的全球公共卫生问题,通过限制抗菌药物使用以降低耐药选择性压力为核心的抗菌药物管理成为应对耐药的主要策略。但是近年来关于限制抗菌药物使用对耐药的有益作用出现许多争议,重要原因之一是研究方法学上缺陷,特别是没有区分医院抗菌药物药敏谱与抗菌药物监测药敏谱,因为前者供临床经验性抗菌治疗参考,后者适用于评价影响耐药的各种因素,包括抗菌药物应用。细菌一旦产生耐药,既有适应性代价机制使其在进化中失去竞争力,恢复敏感性,又有补偿性进化等机制使耐药在菌群中持续,只有深入研究耐药菌分子遗传学和进化机制才有可能找到克服耐药的根本办法。当前需要坚持和改进抗菌药物管理,研发新药、新疗法,将健康中国战略与WHO等国际组织倡导的大健康理念对接,借鉴国际经验,遏制耐药,促进经济社会协调可持续发展。

Antimicrobial resistance(AMR)is a rising public health crisis worldwide.Antimicrobial stewardship,which core is restriction on antimicrobial use to decline selective pressure of AMR,becomes main strategy for tackling AMR.But there are lots of debates about beneficial impact of restriction to antimicrobial use on AMR in recent years.One of the important reasons of the debate is defects on research methodology,especially there are no differentiation between hospital antibiogram and surveillance antibiogram,because the former is used as a reference of empirical antibiotic therapy,and only the latter is appropriate for evaluating factors affecting resistance,including antibiotic use.Once bacteria develop drug resistance,there are both the fitness costs resulting its loss of competitiveness in evolution and restoration of sensitivity to antibiotics,and mechanism of compensatory evolution which allows AMR to persist in bacteria.It is suggested that only by deeply studying the molecular genetics and evolutionary mechanism of drug-resistant bacteria can we find the fundamental way to overcome AMR.At present,we need to adhere to and improve the antimicrobial stewardship,develop new anti-bacterial agents and therapies,connect the Healthy China strategy with the One Health concept advocated by WHO and other international organizations,learn from international experience to curb AMR,and promote coordinated and sustainable economic and social development.