头孢他啶/阿维巴坦耐药肺炎克雷伯菌的体外抗菌药物治疗方案研究

目的 探索对头孢他啶/阿维巴坦耐药的肺炎克雷伯菌体外抗菌药物治疗方案，为临床治疗方案选择提供理论依据。方法 采用PCR对2株肺炎克雷伯菌株可能耐药基因进行鉴定，并对扩增产物进行测序。采用体外时间杀菌试验评估不同抗菌药物单药或联合用药对耐药菌株生长的影响。结果 膜孔蛋白严重缺失和产金属酶分别介导了两菌株对头孢他啶/阿维巴坦耐药；多黏菌素B、亚胺培南、美罗培南和磷霉素单药或两药合并不能显示足够抗菌效果，而多黏菌素B-美罗培南-磷霉素或多黏菌素B-头孢他啶-阿维巴坦三药联合方案可分别对这2株耐药株产生强大持续的杀菌作用。结论 多黏菌素B为基础三药联合可能是对抗具有不同机制介导的头孢他啶/阿维巴坦耐药肺炎克雷伯菌的有效方案。

Study on the in Vitro Antibacterials Therapy of Ceftazidime/Avibactam-resistant Klebsiella Pneumoniae

OBJECTIVE To explore the antibacterial therapy of ceftazidime/avibactam-resistant Klebsiella pneumoniae strains in vitro and to provide a basic theory for the clinical treatment against such resistant strains. METHODS The possible resistance genes of two Klebsiella pneumoniae strains were characterized by PCR, and then the amplicons were sequenced. The effect of monotherapy and combination of the different antibiotics against the resistant strains were evaluated by in vitro time-kill experiments. RESULTS Deficiency of outer membrane porins and production of metallo-beta-lactamase mediated the two strains to ceftazidime/avibatan-resistant, respectively. The time-kill experiment results showed that monotherapy and two-drug combinations of polymyxin B, imipenem, meropenem and fosfomycin could not obtain a satisfactory bactericidal effect. However, the triple therapy of polymyxin B-meropenem-fosfomycin or polymyxin B-ceftazidime-averbactam could produce strong and sustained bactericidal effect on the two drug-resistant strains respectively. CONCLUSION Different triple therapy based on polymyxin B may be an effective strategy against ceftazidime/avibactam-resistant Klebsiella pneumonia strains underlying a different resistant mechanism.