本研究旨在报告来自拉丁美洲27个国家的24,937个最新(2019-2021)肠杆菌临床分离株的参考方法抗菌药物敏感性结果,欧亚大陆,非洲/中东,和亚洲,重点是针对金属β-内酰胺酶(MBL)分离株的研究中氨曲南-阿维巴坦组合。通过CLSI肉汤微量稀释方法进行抗菌素敏感性测试。使用CLSI(2022)断点解释所有药物的最小抑制浓度(MIC),除了氨曲南-阿维巴坦(临时药代动力学/药效学敏感断点,≤8mg/L)和替加环素(US-FDA)。对美罗培南MIC≥2mg/L的分离株进行β-内酰胺酶基因的分子检测,头孢他啶-阿维巴坦MIC≥16mg/L,和/或氨曲南-阿维巴坦MIC≥16mg/L,和50%的大肠杆菌分离株,肺炎克雷伯菌,氧化克雷伯菌,Variicola克雷伯菌,头孢他啶和/或氨曲南MIC≥2mg/L的奇异变形杆菌测试氨曲南-阿维巴坦在≤8mg/L(MIC90,0.25mg/L)时抑制了99.8%的所有肠杆菌,并保持了针对多药耐药(MDR)表型耐药亚群的活性(99.5%敏感),广泛耐药(XDR)(98.7%),耐碳青霉烯类肠杆菌(CRE)(99.1%)。≤8mg/L时,氨曲南-阿维巴坦抑制100%,99.6%,99.6%,KPC的98.8%-,OXA-48-like-,ESBL-,和携带MBL的分离株,分别。MBL阳性分离株在印度最普遍(20.5%),危地马拉(13.8%),和约旦(13.2%)。在评估的全球区域中未观察到氨曲南-阿维巴坦的活性差异。在≤8mg/L的浓度下,氨曲南-阿维巴坦抑制了从发展中国家收集的几乎所有肠杆菌,包括产生MBL的分离株。MBL在肠杆菌中的广泛传播凸显了对诸如氨曲南-阿维巴坦之类的新药用于治疗CRE感染的需求尚未满足。
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 (MIC90, 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.