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阴沟肠杆菌中因获得携带bla的小pHAD28样质粒而导致的头孢他啶/阿维巴坦耐药性

Ceftazidime/avibactam resistance in Enterobacter cloacae due to the acquisition of a small pHAD28-like plasmid harbouring bla.

作者信息

Abril Deisy, Solorzano Paola, Leal Aura Lucía, Forero-Hurtado Daniela, Martínez Oscar, Prada Luisa F, Torres Mildred, Vanegas Gómez Natasha, Escobar-Perez Javier

机构信息

Bacterial Molecular Genetics Laboratory, Universidad El Bosque, Bogota, Colombia.

Bacterial Molecular Genetics Laboratory, Universidad El Bosque, Bogota, Colombia; Departamento de Patologia y Laboratorios, Fundacion Santa Fe de Bogota, Bogota, Colombia.

出版信息

Int J Antimicrob Agents. 2025 Sep;66(3):107540. doi: 10.1016/j.ijantimicag.2025.107540. Epub 2025 May 16.

DOI:10.1016/j.ijantimicag.2025.107540
PMID:40383207
Abstract

OBJECTIVE

Ceftazidime/avibactam (CZA) is a β-lactam/β-lactamase inhibitor combination with potent activity against class A β-lactamases of Gram-negative bacilli. In recent years, its use and the emergence of CZA-resistant isolates have increased worldwide, including in Colombia. This study aimed to determine the resistome of a CZA-resistant Enterobacter cloacae isolate and a mobile genetic element related to the bla gene.

METHODS

The isolate was recovered from a patient with a long hospital stay who had received initial CZA treatment for bla-positive E. cloacae (CZA-susceptible) bacteraemia. Later, the patient suffered a urinary tract infection where a carbapenem- and CZA-resistant E. cloacae (ST456; ≥256/4 µg/mL) was isolated. The genome of 37Ecl06 was sequenced via NovaSeq (Illumina, San Diego, CA, USA.) and MinION (Oxford Nanopore Technologies, Oxford, UK), antibiotic resistance genes were determined with ResFinder and CARD, and mobile genetic elements identified with PlasmidFinder and ISFinder.

RESULTS

Whole-genome sequencing revealed 10 resistance determinants in addition to bla, which was mobilised within the conventional Tn4401b transposon, which in turn appeared to be transposed within a small pHAD28-like plasmid. pHAD28-backbone plasmids have mainly been identified in Salmonella spp. isolates recovered from humans, animals, and food.

CONCLUSION

This is the first report of an E. cloacae isolate harbouring bla. These findings are relevant to continue to understand antimicrobial resistance dissemination mechanisms and to strengthen the One Health approach.

摘要

目的

头孢他啶/阿维巴坦(CZA)是一种β-内酰胺/β-内酰胺酶抑制剂组合,对革兰氏阴性杆菌的A类β-内酰胺酶具有强大活性。近年来,其使用以及CZA耐药菌株的出现在全球范围内有所增加,包括在哥伦比亚。本研究旨在确定一株CZA耐药阴沟肠杆菌分离株的耐药基因组以及与bla基因相关的可移动遗传元件。

方法

该分离株取自一名长期住院患者,该患者最初因bla阳性阴沟肠杆菌(CZA敏感)菌血症接受了CZA治疗。后来,该患者发生尿路感染,从中分离出一株耐碳青霉烯类和CZA的阴沟肠杆菌(ST456;≥256/4 µg/mL)。通过NovaSeq(美国加利福尼亚州圣地亚哥的Illumina公司)和MinION(英国牛津的牛津纳米孔技术公司)对37Ecl06的基因组进行测序,使用ResFinder和CARD确定抗生素耐药基因,使用PlasmidFinder和ISFinder鉴定可移动遗传元件。

结果

全基因组测序显示除bla外还有10个耐药决定簇,bla在传统的Tn4401b转座子内移动,而该转座子又似乎在一个小的类似pHAD28的质粒内转座。pHAD28主干质粒主要在从人、动物和食物中分离出的沙门氏菌属菌株中被鉴定到。

结论

这是关于一株携带bla的阴沟肠杆菌分离株的首次报告。这些发现对于继续了解抗菌药物耐药性传播机制以及加强“同一健康”方法具有重要意义。

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