IHMA, 2122 Palmer Drive, Schaumburg, IL, 60173, USA.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Eur J Clin Microbiol Infect Dis. 2023 Sep;42(9):1135-1143. doi: 10.1007/s10096-023-04645-2. Epub 2023 Aug 1.
This study aimed to report reference method antimicrobial susceptibility results for 24,937 recent (2019-2021) clinical isolates of Enterobacterales from 27 countries in Latin America, Eurasia, Africa/Middle East, and Asia with a focus on the investigational combination aztreonam-avibactam against metallo-β-lactamase (MBL) isolates. Antimicrobial susceptibility testing was performed by the CLSI broth microdilution methodology. Minimum inhibitory concentrations (MICs) were interpreted using the CLSI (2022) breakpoints for all agents except aztreonam-avibactam (provisional pharmacokinetic/pharmacodynamic susceptible breakpoint, ≤ 8 mg/L) and tigecycline (US-FDA). Molecular testing for β-lactamase genes was performed on isolates with meropenem MICs ≥ 2 mg/L, ceftazidime-avibactam MICs ≥ 16 mg/L, and/or aztreonam-avibactam MICs ≥ 16 mg/L, and 50% of isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella variicola, and Proteus mirabilis testing with ceftazidime and/or aztreonam MICs ≥ 2 mg/L. Aztreonam-avibactam inhibited 99.8% of all Enterobacterales at ≤ 8 mg/L (MIC, 0.25 mg/L) and maintained activity against phenotypically resistant subsets of multidrug-resistant (MDR) (99.5% susceptible), extensively drug-resistant (XDR) (98.7%), and carbapenem-resistant Enterobacterales (CRE) (99.1%) isolates. At ≤ 8 mg/L, aztreonam-avibactam inhibited 100%, 99.6%, 99.6%, and 98.8% of KPC-, OXA-48-like-, ESBL-, and MBL-carrying isolates, respectively. MBL-positive isolates were most prevalent in India (20.5%), Guatemala (13.8%), and Jordan (13.2%). No differences in the activity of aztreonam-avibactam were observed across the global regions evaluated. At a concentration of ≤ 8 mg/L, aztreonam-avibactam inhibited almost all Enterobacterales collected from developing countries, including MBL-producing isolates. The widespread dissemination of MBLs among Enterobacterales highlights the unmet need for new agents such as aztreonam-avibactam for the treatment of CRE infections.
本研究旨在报告 2019 年至 2021 年间拉丁美洲、欧亚大陆、非洲/中东和亚洲 27 个国家最近（2019-2021 年）临床分离的肠杆菌目 24937 株的参考方法抗菌药物敏感性结果，重点关注研究性组合药物氨曲南-阿维巴坦对金属β-内酰胺酶（MBL）分离株的作用。抗菌药物敏感性测试采用 CLSI 肉汤微量稀释法进行。除氨曲南-阿维巴坦（暂定药代动力学/药效学敏感折点，≤8mg/L）和替加环素（美国 FDA）外，所有药物的最低抑菌浓度（MIC）均采用 CLSI（2022 年）折点进行解释。对美罗培南 MIC≥2mg/L、头孢他啶-阿维巴坦 MIC≥16mg/L 和/或氨曲南-阿维巴坦 MIC≥16mg/L 的分离株以及 50%的大肠埃希菌、肺炎克雷伯菌、产酸克雷伯菌、奇异变形杆菌和普通变形杆菌的头孢噻肟和/或氨曲南 MIC≥2mg/L 分离株进行β-内酰胺酶基因的分子检测。在≤8mg/L（MIC0.25mg/L）时，氨曲南-阿维巴坦抑制所有肠杆菌目 99.8%，对表型耐药的多药耐药（MDR）（99.5%敏感）、广泛耐药（XDR）（98.7%）和耐碳青霉烯肠杆菌目（CRE）（99.1%）分离株保持活性。在≤8mg/L 时，氨曲南-阿维巴坦抑制 KPC-、OXA-48 样、ESBL-和 MBL 携带株的比例分别为 100%、99.6%、99.6%和 98.8%。MBL 阳性分离株在印度（20.5%）、危地马拉（13.8%）和约旦（13.2%）最为常见。在评估的全球区域中，氨曲南-阿维巴坦的活性没有差异。在≤8mg/L 浓度下，氨曲南-阿维巴坦抑制了来自发展中国家的几乎所有肠杆菌目分离株，包括产 MBL 分离株。肠杆菌目 MBL 的广泛传播突出表明，需要新的药物，如氨曲南-阿维巴坦，来治疗 CRE 感染。
