PDF(Pubmed)
Abstract：
Antimicrobial resistance is a major global health issue. Metallo-β-lactamases (MBL), in particular, are problematic because they can inactivate all classes of β-lactams except aztreonam. Unfortunately, the latter may be simultaneously inactivated by serine β-lactamases. The most dangerous known MBL is New Delhi Metallo-β-lactamase (NDM). This study aimed to test the in vitro susceptibility to aztreonam in combination with novel β-lactamase inhibitors (avibactam, relebactam, and vaborbactam) in clinical strains of Enterobacterales NDM which is resistant to aztreonam. We investigated 21 NDM isolates-including Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii-which are simultaneously resistant to aztreonam, ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam. MICs for aztreonam combinations with novel inhibitors were determined using the gradient strip superposition method. The most effective combination was aztreonam/avibactam, active in 80.95% strains, while combinations with relebactam and vaborbactam were effective in 61.90% and 47.62%, respectively. In three studied strains, none of the studied inhibitors restored aztreonam susceptibility. Aztreonam/avibactam has the most significant antimicrobial potential for NDM isolates. However, combinations with other inhibitors should not be rejected in advance because we identified strain susceptible only to tested combinations with inhibitors other than avibactam. Standardization committees should, as soon as possible, develop official methodology for antimicrobial susceptibility testing for aztreonam with β-lactamase inhibitors.
摘要：
抗菌素耐药性是一个重大的全球卫生问题。金属-β-内酰胺酶（MBL），特别是,是有问题的，因为它们可以使除氨曲南以外的所有类型的β-内酰胺失活。不幸的是,后者可以同时被丝氨酸β-内酰胺酶灭活。已知最危险的MBL是新德里金属-β-内酰胺酶(NDM)。本研究旨在测试氨曲南与新型β-内酰胺酶抑制剂（阿维巴坦，释放巴坦,和vaborbactam）在对氨曲南耐药的肠杆菌NDM临床菌株中。我们调查了21株NDM分离株，包括肺炎克雷伯菌，大肠杆菌,和freundii柠檬酸杆菌-它们同时对氨曲南具有抗性，头孢他啶/阿维巴坦,亚胺培南/雷巴坦，和美罗培南/vaborbactam。使用梯度条带叠加法确定氨曲南与新型抑制剂组合的MIC。最有效的组合是氨曲南/阿维巴坦，在80.95%的菌株中活跃，而雷巴坦和伐巴坦的组合有效率分别为61.90%和47.62%，分别。在三个研究的菌株中，研究的抑制剂均未恢复氨曲南的敏感性。氨曲南/阿维巴坦对NDM分离株具有最显著的抗微生物潜力。然而,不应提前拒绝与其他抑制剂的组合,因为我们确定的菌株仅对除阿维巴坦以外的抑制剂的测试组合敏感.标准化委员会应该，尽快,开发使用β-内酰胺酶抑制剂对氨曲南进行抗菌药敏试验的官方方法。
