Lu Guoping, Tang Hao, Xia Zhaoxin, Yang Wensu, Xu Huaming, Liu Zhen, Ni Shenwang, Wang Zhaofei, Shen Jilu
Department of Laboratory Medicine, The First Affiliated Hospital of Anhui Medical University; Anhui Public Health Clinical Center, Hefei, People's Republic of China.
Department of Laboratory Medicine, The Affiliated Fuyang Hospital of Anhui Medical University, Fuyang, People's Republic of China.
Infect Drug Resist. 2022 Dec 5;15:7107-7116. doi: 10.2147/IDR.S385240. eCollection 2022.
To examine the in vitro and in vivo antimicrobial activities of ceftazidime/avibactam (CZA) alone or in combination with aztreonam (ATM) against KPC-, NDM-, IMP-, KPC+IMP-, KPC+NDM-producing strains.
A total of 67 clinical non-repetitive carbapenem-resistant Enterobacterales (CRE) strains were selected for the microdilution broth method that was performed to analyze the minimal inhibitory concentration (MIC) and the combination antimicrobial susceptibility test using checkerboard titration method. The fractional inhibitory concentration (FIC) was calculated to determine the antimicrobial effect. The time-kill assays and the mouse infection model were used to study the bactericidal effect and therapeutic effect of CZA alone or in combination with ATM.
The CZA minimal inhibitory concentration (MIC) values of CZA revealed that 29 KPC-producing strains and 1 OXA-producing strain were ≤4µg/mL. The CZA MIC values of 37 metal-β-lactamase (MBLs)-producing strains such as NDM-, IMP-, KPC+IMP-, KPC+NDM-producing strains were ≥128µg/mL, after combining with ATM, the FIC values were all below 0.51. The time-kill assays revealed that CZA at various concentrations of 2, 4 and 8 MIC showed significant bactericidal efficiency to the KPC-producing strains. For NDM-, IMP-producing strains, no colony growth was detected after 8 hours of incubation with CZA in combination with ATM. Six percent of the mice in the treatment group and 58% of the mice in the infection group died within 3 days.
Our in vitro results showed that CZA had a good antimicrobial effect on the KPC-producing and OXA-producing strains. CZA combined with ATM showed synergistic bacteriostatic or bactericidal activity against NDM-, IMP-, KPC+IMP-, KPC+NDM-producing strains. The combination of CZA and ATM reduced mortality and prolonged lifespan of mice infected with NDM-, IMP-, KPC+IMP-, and KPC+NDM-producing strains, which provides fundamental knowledge for improving treatment strategies and initializing clinical trials.
研究头孢他啶/阿维巴坦（CZA）单独或与氨曲南（ATM）联合对产KPC、NDM、IMP、KPC+IMP、KPC+NDM菌株的体外和体内抗菌活性。
共选择67株临床非重复性耐碳青霉烯类肠杆菌科细菌（CRE）菌株，采用微量肉汤稀释法分析最低抑菌浓度（MIC），并使用棋盘滴定法进行联合抗菌药敏试验。计算部分抑菌浓度（FIC）以确定抗菌效果。采用时间杀菌试验和小鼠感染模型研究CZA单独或与ATM联合的杀菌效果和治疗效果。
CZA的最低抑菌浓度（MIC）值显示，29株产KPC菌株和1株产OXA菌株≤4μg/mL。37株产金属β-内酰胺酶（MBL）菌株（如产NDM、IMP、KPC+IMP、KPC+NDM菌株）的CZA MIC值≥128μg/mL，与ATM联合后，FIC值均低于0.51。时间杀菌试验表明，2、4和8倍MIC的不同浓度CZA对产KPC菌株显示出显著的杀菌效率。对于产NDM、IMP菌株，与CZA联合ATM孵育8小时后未检测到菌落生长。治疗组6%的小鼠和感染组58%的小鼠在3天内死亡。
我们的体外结果表明，CZA对产KPC和产OXA菌株具有良好的抗菌效果。CZA与ATM联合对产NDM、IMP、KPC+IMP、KPC+NDM菌株显示出协同抑菌或杀菌活性。CZA和ATM联合降低了感染产NDM、IMP、KPC+IMP和KPC+NDM菌株小鼠的死亡率并延长了其生存期，这为改进治疗策略和启动临床试验提供了基础知识。
Zotero 插件
