Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States.
Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States.
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在美国抗碳青霉烯的肠杆菌中，colistin杂素的异质抗性在很大程度上未被发现。
DOI：
10.1128/mbio.02881-20
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发表时间：
2021-01-26
期刊：
影响因子：
6.4
通讯作者：
Weiss DS
中科院分区：
文献类型：
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作者：
Band VI;Satola SW;Smith RD;Hufnagel DA;Bower C;Conley AB;Rishishwar L;Dale SE;Hardy DJ;Vargas RL;Dumyati G;Kainer MA;Phipps EC;Pierce R;Wilson LE;Sorensen M;Nilsson E;Jordan IK;Burd EM;Farley MM;Jacob JT;Ernst RK;Weiss DS
异源耐药是一种未被充分认识的现象，可能是一些原因不明的抗生素治疗失败的原因。将异源耐药分离株错误分类为敏感分离株可能导致不适当的治疗。异源耐药性是抗生素耐药性的一种形式，其中细菌菌株由次要耐药亚群和主要敏感亚群组成。我们先前表明，粘菌素异源耐药性可以介导体内感染模型中粘菌素治疗的失败，即使是临床诊断指定为易感的分离株。我们试图描述高度耐药的碳青霉烯类耐药肠球菌（CRE）中粘菌素异质耐药的程度。我们筛选了408株菌株的粘菌素异源耐药性。这些分离株于2012年至2015年在美国8个州收集，作为CRE主动监测的一部分。粘菌素异质耐药率为10.1%（41/408），高于传统的同质耐药率（7.1%，29/408）。大多数（93.2%，38/41）的这些异源耐药菌株被归类为敏感的标准临床诊断测试粘菌素。粘菌素异源耐药的频率在2015年最高，这是该研究的最后一年。这在肠杆菌属分离株中尤其如此，其中特定菌种的异源耐药率最高。在肺炎克雷伯氏菌分离株中（占检测分离株的大多数），存在一个密切相关的粘菌素异质耐药ST-258分离株簇，主要在格鲁吉亚发现。然而，分支分析表明，总体而言，异源抗性K的遗传背景有显着的多样性。肺炎分离株。这些发现表明，由于在临床上很大程度上未被检测到，在美国，CRE中的粘菌素异源耐药性未被充分认识。
Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy. Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States.