Abstract:Objective: To evaluate the antibacterial activity of amtraxam (ATM) combined with Ceftazidime/avibactam (CZA) against carbapenem resistant enterobacter cloacae complex group in vitro, and to analyze the production and genotype distribution of carbapenase in CRECC. Methods: A total of 46 CRECC strains were collected from 2021 to 2023. The combined antibacterial effect of ATM and CZA was evaluated by microbroth dilution checkerboard method, and the type of action was determined according to fractional inhibitory concentration (FIC). The modified carbapenem inactivation method (mCIM) and EDTA modified carbapenem inactivation method (eCIM) were used to confirm whether the strain produced carbapenase and preliminatively distinguish class A and Class B carbapenase, and the carbapenase genotypes were further confirmed by immunochromatography. Results: In 46 strains of CRECC, ATM combined with CZA showed synergistic effect (FIC≤0.5) in 39 strains, additive effect (0.5<FIC≤1) in 7 strains, no unrelated or antagonistic effect was found. The minimum inhibitory concentration (MIC) of ATM decreased significantly from 256 mg/L to 0.008 mg/L, which was reduced by 32,000 times. The MIC of CZA was reduced from 64 mg/L to 0.015 mg/L, a 4,267-fold decrease. Carbapenase genotype analysis confirmed that 38 of 46 CRECC strains produced carbapenase NDM (82.61%), and 8 strains did not produce carbapenase (17.39%). The combination of ATM and CZA showed synergistic effect (31 strains, 81.58%) or additive effect (7 strains, 18.42%) in 38 enzyme-producing strains, and synergistic effect in 8 strains without enzyme-producing CRECC strains. Conclusion: The popular CRECC in this region mainly produces NDM carbapenemase. ATM combined with CZA showed significant antibacterial activity against CRECC in vitro. The combination regimen has shown promising potential in combating CRECC and is expected to be an effective regimen for the treatment of such infections. In the future, it is necessary to further study the clinical application effect and safety to optimize the treatment strategy.
[1] Davin-Regli A,Lavigne J P,Pages J M.Enterobacter spp.:update on taxonomy,clinical aspects,and emerging antimicrobial resistance[J].Clin Microbiol Rev,2019,32(4):2-19. [2] 员静,单斌,孟雪斐,等.2018-2020年多中心耐碳青霉烯类肠杆菌目细菌的流行病学特征及耐药性分析[J].中国抗生素杂志,2021,46(11):1038-1043. [3] Mavroidi A,Froukala E,Tsakris A.Comparative genomics of an emerging multidrug-resistant blaNDM-carrying ST182 lineage in Enterobacter cloacae complex[J].Antibiotics (Basel),2024,13(6):535. [4] Liu Y,Kim D W,Lee J H,et al.Perspectives on metallo-β-lactamase inhibitors:challenges and implications of metallo-β-lactamase variants[J].Iran Public Health,2024,53(10):2389-2391. [5] 张晓辉,李敏,王明,等.氨曲南联合头孢他啶-阿维巴坦对产金属β-内酰胺酶肺炎克雷伯菌和铜绿假单胞菌的体外抗菌活性研究[J].中国感染控制杂志,2022,21(5):437-442. [6] Pages J M,Pescatori M,Rodrigues A,et al.The complex regulation of porinpermeability in Enterobacteriaceae:from homeostatic control of membrane permeability to the optimization of antibiotic uptake[J].Antimicrob Chemother,2021,76(1):1-11. [7] Du D,Wang-Kan X,Neuenschwander A,et al.Multidrug efflux pumps:structure,function and regulation[J].Nat Rev Microbiol,2018,16(9):523-539. [8] 顾全,柳朔怡,韩素桂,等.我院耐碳青霉烯类阴沟肠杆菌耐药机制与同源性分析[J].标记免疫分析与临床,2022,29(9):1501-1506. [9] Cai Y,Chen C,Zhao M,et al.High prevalence of metallo-β-lactamase-producing Enterobacter cloacae from three tertiary hospitals in China[J].FrontMicrobiol,2019(10):1610. [10] 陈善健,郑芷怡,林宇岚,等.胶体金免疫层析法在产碳青霉烯酶肠杆菌目细菌检测中的应用评价[J].临床检验杂志,2023,41(2):96-99.