Liao Quanfeng, Deng Jin, Feng Yu, Zhang Weili, Wu Siying, Liu Ya, Che Huijuan, Xie Yi
Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
J Infect Public Health. 2022 May;15(5):545-549. doi: 10.1016/j.jiph.2022.04.002. Epub 2022 Apr 9.
Klebsiella pneumoniae carbapenemase (KPC)-producing K.pneumoniae has represented a serious health problem in worldwide. The resistance to ceftazidime-avibactam (CAZ-AVI) began to emerge since its approval in 2015. We aim to explore the resistance mechanism of CAZ-AVI.
Phenotypic test and whole-genome sequencing (WGS) analysis were performed in KP-HX0917 and KP-HX1016 Klebsiella pneumoniae isolates, collected from the same patient following treatment with CAZ-AVI.
We report a case of emergence of CAZ-AVI resistance in ST 11 KPC-2-producing K. pneumoniae (KP-HX1016) during 14 days of exposure with CZA-AVI. Molecular analysis highlighted the A533C mutation in the blaKPC-2 gene, resulting a D179A substitution in protein sequence, which restored the hydrolysis ability of imipenem and meropenem, but not for ertapenem, and the result of phenotypic test was negative. However, KP-HX0917 produced serine-carbapenemase by phenotypic detection and lost its capacity of hydrolyzing carbapenems.
The emergence of CAZ-AVI resistance should arouse our attention, the susceptibility testing should be followed by a combination of phenotypic and molecular methods, to make sure that no potential carbapenemase-producing bacteria are missed.
产肺炎克雷伯菌碳青霉烯酶（KPC）的肺炎克雷伯菌已成为全球严重的健康问题。自2015年获批以来，对头孢他啶-阿维巴坦（CAZ-AVI）的耐药性开始出现。我们旨在探究CAZ-AVI的耐药机制。
对从同一患者身上收集的肺炎克雷伯菌分离株KP-HX0917和KP-HX1016进行表型试验和全基因组测序（WGS）分析，这些分离株在接受CAZ-AVI治疗后获得。
我们报告了1例在使用CZA-AVI治疗14天期间，ST11型产KPC-2的肺炎克雷伯菌（KP-HX1016）出现CAZ-AVI耐药的病例。分子分析突出显示blaKPC-2基因中的A533C突变，导致蛋白质序列中的D179A替代，这恢复了亚胺培南和美罗培南的水解能力，但对厄他培南无效，且表型试验结果为阴性。然而，KP-HX0917通过表型检测产生丝氨酸碳青霉烯酶并丧失了水解碳青霉烯类的能力。
CAZ-AVI耐药性的出现应引起我们的关注，药敏试验应结合表型和分子方法，以确保不漏检任何潜在的产碳青霉烯酶细菌。
