Assefa Getnet M, Roberts Jason A, Aslan Abdullah T, Mohammed Solomon A, Sime Fekade B
Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia.
J Antimicrob Chemother. 2025 Feb 3;80(2):334-346. doi: 10.1093/jac/dkae451.
Carbapenem-resistant Gram-negative bacteria (CR-GNB) develop resistance to many antimicrobials. To effectively manage infections caused by these organisms, novel agents and/or combinations of antimicrobials are required.
Evaluated the in vitro efficacy of ceftazidime/avibactam in combination with other antimicrobials against CR-GNB.
PubMed, Web of Science, Embase and Scopus were searched. Study outcomes were quantified by counting the number of isolates exhibiting synergy, defined as a fractional inhibitory concentration index ≤ 0.5 for checkerboard and Etest, and a >2 log cfu/mL reduction for time-kill studies. The proportion of synergy was calculated as the ratio of isolates exhibiting synergy to the total number of isolates tested. These proportions were analysed using a random-effects model, following the Freeman-Tukey double-arcsine transformation.
Forty-five in vitro studies were included. A total of 734 isolates were tested, and 69.3% of them were resistant to ceftazidime/avibactam. The combination of ceftazidime/avibactam with aztreonam showed a high synergy rate against carbapenem-resistant Klebsiella pneumoniae (effect size, ES = 0.91-0.98) and Escherichia coli (ES = 0.75-1.00). Ceftazidime/avibactam also demonstrated a high synergy rate (ES = 1) in time-kill studies when combined with azithromycin, fosfomycin and gentamicin against K. pneumoniae. Compared to ceftazidime/avibactam alone, a higher bactericidal rate was reported when ceftazidime/avibactam was combined with other antimicrobials against carbapenem-resistant K. pneumoniae (57% versus 31%) and E. coli (93% versus 0%).
Ceftazidime/avibactam frequently demonstrates synergistic bactericidal activity when combined with various antimicrobials against CR-GNB in in vitro tests. Further pre-clinical and clinical studies are warranted to validate the utility of ceftazidime/avibactam-based combination regimens for CR-GNB infections.
耐碳青霉烯类革兰氏阴性菌（CR-GNB）对多种抗菌药物产生耐药性。为有效控制由这些病原体引起的感染，需要新型抗菌药物和/或抗菌药物组合。
评估头孢他啶/阿维巴坦与其他抗菌药物联合使用对CR-GNB的体外抗菌效果。
检索了PubMed、科学网、Embase和Scopus数据库。通过计算表现出协同作用的分离株数量来量化研究结果，协同作用定义为棋盘法和Etest的分数抑菌浓度指数≤0.5，以及时间杀菌研究中菌落形成单位/mL减少>2 log。协同作用的比例计算为表现出协同作用的分离株数量与测试的分离株总数之比。在进行Freeman-Tukey双反正弦变换后，使用随机效应模型分析这些比例。
纳入了45项体外研究。共测试了734株分离株，其中69.3%对头孢他啶/阿维巴坦耐药。头孢他啶/阿维巴坦与氨曲南联合使用对耐碳青霉烯类肺炎克雷伯菌（效应大小，ES = 0.91 - 0.98）和大肠杆菌（ES = 0.75 - 1.00）显示出较高的协同率。在时间杀菌研究中，头孢他啶/阿维巴坦与阿奇霉素、磷霉素和庆大霉素联合使用对肺炎克雷伯菌也显示出较高的协同率（ES = 1）。与单独使用头孢他啶/阿维巴坦相比，头孢他啶/阿维巴坦与其他抗菌药物联合使用对耐碳青霉烯类肺炎克雷伯菌（57%对31%）和大肠杆菌（93%对0%）的杀菌率更高。
在体外试验中，头孢他啶/阿维巴坦与多种抗菌药物联合使用时，经常表现出协同杀菌活性。有必要进一步开展临床前和临床研究，以验证基于头孢他啶/阿维巴坦的联合治疗方案对CR-GNB感染的效用。
