艰难梭菌抗菌药物耐药机制研究进展

Progress on mechanisms of antibiotic resistance in Clostridioides difficile

艰难梭菌(Clostridioides difficil,CD)是医疗机构感染性腹泻最常见的病原之一,并被美国疾病控制和预防中心列为需要紧急和积极应对的耐药威胁。许多耐药基因可在医疗机构、社区和自然环境中不同菌种间转移,随着新耐药机制的产生与获得,CD的抗微生物药物耐药性(antimicrobial resistance,AMR)也在不断演变。CD的耐药机制多种多样,包括化学修饰造成失效、药物靶点的修饰以及药物的主动外排等。既往CD对大环内脂类和喹诺酮类药物耐药性及耐药机制研究较为充分,但对甲硝唑、万古霉素等艰难梭菌感染(Clostridioides difficile infection,CDI)治疗药物的耐药机制研究尚处于起步阶段。近年来研究发现,一些既往CD研究中未考虑的机制如质粒介导的耐药,同样可能在艰难梭菌AMR中发挥重要作用。本文主要综述了CD对甲硝唑、万古霉素和非达霉素等治疗用抗菌药物的耐药机制研究进展,以期为CDI的防治与新抗菌药物和新耐药菌检测试剂盒的研发提供参考。

Clostridioides difficile(CD)is one of the most common pathogens causing health-care-associated infectious diarrhea and is listed by the U.S.Centers for Disease Control and Prevention as an urgent antibiotic resistance(AR)threat.Many resistance genes can be transferred between different CD strains present in the clinical setting,community,and environment.The antimicrobial resistance(AMR)of CD continues to evolve with the emergence and acquisition of new drug resistance mechanisms.CD has developed diverse drug resistance mechanisms,such as drug alteration,modification of the target site,and extrusion of drugs via efflux pumps.Researches have provided comprehensive knowledge about resistance mechanisms of macrolides and quinolones in CD.However,the mechanisms of resistance for metronidazole,vancomycin,and other therapeutic antibiotics against Clostridioides difficile infection(CDI)are only beginning to be elucidated.Some previously unfound mechanisms,such as plasmid-mediated drug resistance in CD,may also play an important role.In this review,we summarize the research progress on drug resistance mechanisms of CD with antimicrobial drugs already used clinically,such as metronidazole,vancomycin,and fidaxomicin,thereby providing the references for the clinical treatment and prevention of CDI,as well as the development of new antibacterial drugs and detection kits for drug resistant bacteria.