头孢他啶/阿维巴坦对耐碳青霉烯肠杆菌科细菌的体外抗菌活性研究

目的 头孢他啶/阿维巴坦(CAZ/AVI)是第三代头孢菌素和新型的非β-内酰胺酶类的β-内酰胺酶抑制剂阿维巴坦相 结合的抗生素，对多重耐药菌具有抗菌活性，本研究评价CAZ/AVI对临床分离耐碳青霉烯肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae，CRE)的体外抗菌活性，同时评价CAZ/AVI对不同菌属的CRE菌和携带不同耐药基因型的CRE菌的体外抗菌 活性。方法 对收集来自解放军302医院和宁夏医科大学总医院2008年1月至2017年12月临床分离的266株CRE菌株进行了最低抑 菌浓度(minimum bacteriostatic concentration, MIC)的测定；采用特异引物扩增法进行耐药基因型的测定，进一步分析CAZ/AVI对 携带不同耐药基因型的CRE菌的体外抗菌活性。结果 CAZ/AVI体对临床分离CRE菌的体外抑菌活性为49.62%，明显优于头孢 他啶和其他对照药物(P=0)，但弱于多黏菌素B和替加环素(P=0.003)；对克雷伯菌属CRE菌的体外抑菌效果明显，可达到63.75% 的体外活性抑菌率，其次为肠杆菌属CRE菌(23.81%)，对埃希菌属CRE菌的体外抑菌率最低(13.33%)；对于携带blaKPC-2 基因型 的CRE菌株体外抑菌率可达到69.23%，而对于携带blaNDM 和blaIMP 的基因型的CRE菌株作用相当(P=0.889)，体外抑菌率分别为 2.22%和8.33%。结论 CAZ/AVI坦对CRE菌表现出了一定的体外抗菌活性优势，尤其是增强了头孢他啶的体外抗菌活性。对克 雷伯菌属CRE菌的体外抑菌活性明显，并且能够很好的抑制携带blaKPC-2 基因型的CRE菌。

Study on in vitro antimicrobial activities of ceftazidime/avibactam to carbapenemresistant Enterobacteriaceae

Objective Ceftazidime/avibactam(CAZ/AVI) is a combination of cephalosporin and a novel betalactamase inhibitor—avibactam with antibacterial activities against multi-drug resistant bacteria. This study was to evaluate the in vitro antimicrobial activities of CAZ/AVI against carbapenem-resistant Enterobacteriaceae (CRE) isolated from clinical samples and investigate the in vitro antibacterial activities of CAZ/AVI against different CRE genus and the isolated CRE carrying different resistant genotypes. Methods Minimum bacteriostatic concentrations (MIC) of CAZ/AVI against 266 strains of pathogenic bacteria isolated from clinical samples in the 302th hospital of PLA and general hospital of Ningxia Medical University during Janurary 2008 to December 2017 were determined. In vitro antimicrobial activities of CAZ/AVI against CRE strains with different resistant genotypes was further analyzed using specific primer amplification. Results The in vitro antibacterial activities of CAZ/AVI against clinically isolated CRE reached 49.62%, significantly better than that of ceftazidime and other control drugs (P=0), but weaker than that of polymyxin B and tigecycline (P=0.003). The in vitro bacteriostatic effects on Klebsiella spp. of CRE reached 63.75% in vitro, followed by Enterobacter spp. of CRE which reached 23.81%, and Escherichia spp. of CRE reached only 13.33%, which was the lowest. For CRE strains carrying KPC-2 genotypes, the bacteriostatic rate was 69.23% in vitro, the CRE strains carrying blaNDM and blaIMP genotypes had the same effects (P=0.889), and the inhibition rates in vitro were 2.22% and 8.33%, respectively. Conclusion CAZ/AVI had certain antibacterial activities against CER bacteria in vitro, especially enhanced the antibacterial activities of ceftazidime in vitro. CAZ/ AVI demonstrated significant antibacterial activities against Klebsiella spp. in vitro and could inhibit CRE strains carrying KPC-2 genotypes very