头孢他啶/阿维巴坦联合不同抗菌药物对产金属酶肠杆菌目细菌体外活性分析  

In vitro activity analysis of ceftazidime/avibactam combined with different antimicrobial drugs on metallozyme-producing Enterobacterales

作　　者：董小雪 张鸿娟[1,2] 苏艳丹 李欣玥[1,2] 许云敏 朱晓雁 郭兰花[3] 单斌 Dong Xiaoxue;Zhang Hongjuan;Su Yandan;Li Xinyue;Xu Yunmin;Zhu Xiaoyan;Guo Lanhua;Shan Bin(Department of Clinical Laboratory,the First Affiliated Hospital of Kunming Medical University,Kunming 650032;Yunnan Province Clinical Research Center for Laboratory Medicine,Kunming,650032;Shizong County People’s Hospital,Shizong 655700)

机构地区：[1]昆明医科大学第一附属医院医学检验科,昆明650032 [2]云南省医学检验临床医学研究中心,昆明650032 [3]师宗县人民医院,师宗655700

出　　处：《中国抗生素杂志》2024年第10期1101-1106,共6页Chinese Journal of Antibiotics

基　　金：云南省“兴滇英才支持计划”(No.XDYC-MY-2022-0063);云南省科技厅-昆明医科大学应用基础研究联合专项(No.202301AY070001-291);云南省/昆医大附一院重大科技专项(No.2023zdpy05)。

摘　　要：目的研究头孢他啶/阿维巴坦联合氨曲南、亚胺培南和美罗培南对产金属酶肠杆菌目细菌的体外抑菌活性,为临床产金属酶肠杆菌目细菌的治疗提供依据。方法收集昆明医科大学第一附属医院2022年8月—2023年8月碳青霉烯类耐药肠杆菌目细菌,PCR方法检测bla_(KPC)、bla_(OXA-48)、bla_(VIM)、bla_(NDM)和bla_(IMP)等5种耐药基因,应用微量肉汤稀释法检测头孢他啶/阿维巴坦、氨曲南、亚胺培南和美罗培南的最低抑菌浓度,棋盘法检测头孢他啶/阿维巴坦联合氨曲南、亚胺培南和美罗培南的协同抑菌活性,计算联合药敏的部分抑菌浓度指数和敏感折点指数,判断两种组合之间的协同、相加、无关或拮抗作用,评估不同组合之间的协同效果。结果本研究共收集耐碳青霉烯类肠杆菌目细菌234株,其中产金属酶的菌株占12.8%(30/234),对头孢他啶/阿维巴坦的耐药率为100%(30/30)。分别从不同样本类型中选择6株产金属酶的代表性菌株进行联合药敏实验,结果头孢他啶/阿维巴坦联合氨曲南对6株菌株部分抑菌浓度指数均<0.5,表现出协同作用,协同率为100%(6/6),联合美罗培南和亚胺培南时,每个组合仅对1株菌株表现出协同作用,协同率为16.7%(1/6),但在美罗培南的组合中,有3株菌株表现出相加作用,相加率为50%(3/6),对2株双酶型菌株均无协同或相加作用,敏感折点指数头孢他啶/阿维巴坦联合氨曲南明显优于亚胺培南和美罗培南,协同效果显著。结论体外联合药敏结果显示,对产金属酶肠杆菌目细菌,头孢他啶/阿维巴坦联合氨曲南具有显著的协同效果,联合美罗培南和亚胺培南协同效果不明显,因此头孢他啶/阿维巴坦联合氨曲南可作为治疗产金属酶肠杆菌感染的方案之一。Objective To study the in vitro antibacterial activity of ceftazidime/avibactam combined with aztreonam,imipenem,and meropenem against metalloenzyme-producing Enterobacterales,and provide a basis for the clinical treatment of metalloenzyme-producing Enterobacterales.Methods Carbapenem-resistant Enterobacterales were collected from the First Affiliated Hospital of Kunming Medical University from August 2022 to August 2023,and five drug resistance genes(bla_(KPC),bla_(OXA-48),bla_(VIM),bla_(NDM),and bla_(IMP))were detected by the PCR method.The minimum inhibitory concentrations of ceftazidime/avibactam,aztreonam,imipenem,and meropenem were detected by the microbroth dilution method.The checkerboard method was used to detect the synergistic antibacterial activity of ceftazidime/avibactam combined with aztreonam,imipenem and meropenem.The partial inhibitory concentration index and sensitive breakpoint index of the combined drug susceptibility were calculated to judge the synergistic,additive,irrelevant or antagonistic effect between the two combinations,and to evaluate the synergistic effect between the different combinations.Results A total of 234 carbapenem-resistant strains of Enterobacterales were collected,of which 12.8%(30/234)were metalloenzyme-producing strains and 100%(30/30)were resistant to ceftazidime/avibactam.Six representative strains producing metalloenzymes were selected from different sample types for combined antimicrobial susceptibility experiments.A synergistic effect between ceftazidime/avibactam and aztreonam was observed in 6/6(100%)of the strains,with partial inhibitory concentration indices smaller than 0.5.When combined with meropenem and imipenem,each combination showed a synergistic effect on only 1 strain,and the synergistic rate was 16.7%(1/6).However,in the combination of meropenem,3 strains showed an additive effect,and the additive rate was 50%(3/6),and the 2 strains of the double enzyme type strain had no synergistic or additive effect.The sensitive breakpoint index of ceftazidime/a

关 键 词：联合药敏实验 碳青霉烯类 多重耐药 协同抑菌活性 金属酶 

分 类 号：R978.1[医药卫生—药品]