Practical Agar-Based Disk Diffusion Tests Using Sulfamoyl Heteroarylcarboxylic Acids for Identification of Subclass B1 Metallo-β-Lactamase-Producing <i>Enterobacterales</i>
Practical Agar-Based Disk Diffusion Tests Using Sulfamoyl Heteroarylcarboxylic Acids for Identification of Subclass B1 Metallo-β-Lactamase-Producing <i>Enterobacterales</i>
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使用磺胺酰杂芳基羧酸进行实用琼脂纸片扩散试验，鉴定产金属-β-内酰胺酶 B1 亚类<i>肠杆菌</i>
DOI：
10.1128/jcm.00761-21
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发表时间：
2021
影响因子：
9.4
通讯作者：
Arakawa Yoshichika
中科院分区：
文献类型：
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作者：
Norizuki Chihiro;Wachino Jun-ichi;Jin Wanchun;Kimura Kouji;Kawamura Kumiko;Nagano Noriyuki;Arakawa Yoshichika
产碳青霉烯酶肠球菌（CPE）的全球分布是一个严重的公共卫生问题，因为它们表现出碳青霉烯耐药性，从而限制了治疗CPE感染的抗菌药物的选择。β-内酰胺和一种新批准的β-内酰胺酶抑制剂（如阿维巴坦、阿替巴坦或伐硼巴坦）联合治疗为科普CPE提供了一种有价值的工具;然而，这些抑制剂仅对丝氨酸型碳青霉烯酶有效，对金属β-内酰胺酶（MβLs）无效。因此，重要的是通过使用简单可靠的方法容易地区分CPE产生的碳青霉烯酶，以选择适当的治疗。我们开发了三种实用的琼脂纸片扩散试验（双纸片协同试验[DDST]、纸片增强试验和改良碳青霉烯灭活法[mCIM]）来区分B1亚类MβLs（如IMP-、NDM-和VIM-型MβLs）与其他碳青霉烯酶（尤其是丝氨酸型碳青霉烯酶）的产生。这是使用我们最初开发的B1 Mβ L特异性氨磺酰基杂芳基羧酸抑制剂2，5-二甲基-4-氨磺酰基呋喃-3-羧酸（SFC）和2，5-二乙基-1-甲基-4-氨磺酰基吡咯-3-羧酸（SPC）来实现的。用SFC和SPC建立的DDST和mCIM对产B1 Mβ L的肠球菌的敏感性和特异性分别为95.3%和100%。在纸片增强试验中，SFC和SPC的敏感性分别为89.1%和93.8%，而两者的特异性均为100%。这些方法简单、廉价，准确率高。因此，这些方法对于临床微生物实验室特异性检测和区分产B1 Mβ L的肠球菌具有巨大的帮助，并将导致在临床环境中更好地预防此类多重耐药细菌的感染。
The worldwide distribution of carbapenemase-producingEnterobacterales(CPE) is a serious public health concern as they exhibit carbapenem resistance, thus limiting the choice of antimicrobials for treating CPE infections. Combination treatment with a β-lactam and one of the newly approved β-lactamase inhibitors, such as avibactam, relebactam, or vaborbactam, provides a valuable tool to cope with CPE; however, these inhibitors are active only against serine-type carbapenemases and not against metallo-β-lactamases (MβLs). Therefore, it is important to readily differentiate carbapenemases produced by CPE by using simple and reliable methods in order to choose an appropriate treatment. Here, we developed three practical agar-based disk diffusion tests (double-disk synergy test [DDST], disk potentiation test, and modified carbapenem inactivation method [mCIM]) to discriminate the production of subclass B1 MβLs, such as IMP-, NDM-, and VIM-type MβLs, from the other carbapenemases, especially serine-type carbapenemases. This was accomplished using B1 MβL-specific sulfamoyl heteroarylcarboxylic acid inhibitors, 2,5-dimethyl-4-sulfamoylfuran-3-carboxylic acid (SFC) and 2,5-diethyl-1-methyl-4-sulfamoylpyrrole-3-carboxylic acid (SPC), originally developed by us. The DDST and mCIM using SFC and SPC revealed high sensitivity (95.3%) and specificity (100%) in detecting B1 MβL-producingEnterobacterales. In the disk potentiation test, the sensitivities using SFC and SPC were 89.1% and 93.8%, respectively, whereas the specificities for both were 100%. These methods are simple and inexpensive and have a high accuracy rate. These methods would therefore be of immense assistance in the specific detection and discrimination of B1 MβL-producingEnterobacteralesin clinical microbiology laboratories and would lead to better prevention against infection with such multidrug-resistant bacteria in clinical settings.