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用3种不同方法研究头孢他啶-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分离株的协同作用。

Investigation of the synergistic effect of ceftazidime-avibactam and aztreonam combination on carbapenem-resistant Klebsiella pneumoniae isolates with 3 different methods.

作者信息

Uzunöner Yasemin, Kansak Nilgün, Aksaray Sebahat

机构信息

1Haydarpasa Numune Training and Research Hospital, Laboratory of Medical Microbiology, University of Health Sciences, Istanbul, Turkey.

2Department of Medical Microbiology, Hamidiye Medical Faculty, University of Health Sciences, Istanbul, Turkey.

出版信息

Acta Microbiol Immunol Hung. 2024 Dec 17;71(4):308-314. doi: 10.1556/030.2024.02395. Print 2024 Dec 19.

Abstract

Treatment options are limited for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates due to the production of metallo-β-lactamase (MBL). The ceftazidime-avibactam (CZA)/ aztreonam (ATM) combination represents a new therapeutic approach in MBL-positive isolates. Our study aims to determine distribution of carbapenemase genes in CRKP isolates and to investigate the in vitro synergistic effect of the CZA/ATM combination.Our study included 48 CRKP strains isolated from various clinical samples. Identification was performed using MALDI-TOF MS (bioMérieux, France), and susceptibility was tested with Vitek-2 (bioMérieux). The susceptibility to CZA and ATM was determined using CZA 30/20 µg and ATM 30 µg (Oxoid™,UK) disks. Carbapenemase genes VIM, NDM, IMP, KPC, OXA-23, OXA-58, OXA-48, and OXA-51 were investigated in only 44 isolates using the Bio-Speedy Carbapenem resistance qPCR (Bioexen, Turkiye) kit. Synergy testing was evaluated with double disk diffusion, gradient strip (bioMérieux)/disk diffusion, and broth disk elution methods.Out of 48 carbapenem-resistant isolates, 40 (83.3%) isolates showed resistance to CZA and 46 (95.8%) to aztreonam. Synergy was detected with all three methods in all isolates identified as resistant to CZA, CZA-sensitive isolates were not included in this evaluation. The most frequently detected carbapenemase genes were NDM+OXA-48, found in 28 (63.6%) of the isolates.Although the NDM+OXA-48 coexistence predominates in our center, in vitro synergy between CZA and ATM was detected in all of CZA-resistant isolates. Performing the CZA+ATM synergy test and reporting the result is crucial for choosing appropriate treatment in CRKP infection.

摘要

由于金属β-内酰胺酶(MBL)的产生,对于由耐碳青霉烯类肺炎克雷伯菌(CRKP)分离株引起的感染,治疗选择有限。头孢他啶-阿维巴坦(CZA)/氨曲南(ATM)联合用药是针对MBL阳性分离株的一种新的治疗方法。我们的研究旨在确定CRKP分离株中碳青霉烯酶基因的分布,并研究CZA/ATM联合用药的体外协同作用。我们的研究纳入了从各种临床样本中分离出的48株CRKP菌株。使用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS,法国生物梅里埃公司)进行鉴定,并用Vitek-2(生物梅里埃公司)检测药敏情况。使用CZA 30/20 μg和ATM 30 μg(英国Oxoid™)药敏纸片测定对CZA和ATM的敏感性。仅使用Bio-Speedy碳青霉烯耐药qPCR(土耳其Bioexen)试剂盒对44株分离株检测碳青霉烯酶基因VIM、NDM、IMP、KPC、OXA-23、OXA-58、OXA-48和OXA-51。采用双纸片扩散法、梯度纸条(生物梅里埃公司)/纸片扩散法和肉汤纸片洗脱法评估协同试验。在48株耐碳青霉烯类分离株中,40株(83.3%)对CZA耐药,46株(95.8%)对氨曲南耐药。在所有被鉴定为对CZA耐药的分离株中,三种方法均检测到协同作用,对CZA敏感的分离株未纳入该评估。最常检测到的碳青霉烯酶基因是NDM+OXA-48,在28株(63.6%)分离株中发现。尽管在我们中心NDM+OXA-48共存占主导,但在所有对CZA耐药的分离株中均检测到CZA和ATM之间的体外协同作用。进行CZA+ATM协同试验并报告结果对于选择CRKP感染的合适治疗方法至关重要。

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