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日本东京一家癌症中心发生涉及多个 IMP 生产肠杆菌科 cloacae 复合序列类型 78 群的多克隆爆发。

Institutional outbreak involving multiple clades of IMP-producing Enterobacter cloacae complex sequence type 78 at a cancer center in Tokyo, Japan.

机构信息

Department of Infection Control and Prevention, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Department of Infectious Diseases, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.

出版信息

BMC Infect Dis. 2021 Mar 22;21(1):289. doi: 10.1186/s12879-021-05952-9.

Abstract

BACKGROUND

Information about the clinical and microbiological characteristics of IMP-producing Enterobacterales has been limited. Here, we describe an institutional outbreak of IMP-producing Enterobacter cloacae complex (ECC) involving multiple clades of ECC sequence type (ST) 78 strains.

METHODS

Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation experiments of 18 IMP-producing ECC strains isolated during four-year study period were performed. Species and subspecies were determined by average nucleotide identity analysis and clonal relatedness of the isolates was analyzed with multilocus sequence typing and core-genome single nucleotide polymorphism (SNP) analysis. Relevant clinical information was extracted from medical records.

RESULTS

Fourteen of 18 IMP-producing ECC isolates were determined as Enterobacter hormaechei ST78. Sixteen isolates, including 13 isolates belonging to ST78, carried bla in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carrying bla on IncHI2 plasmids and for an isolate carrying bla on an IncL/M plasmid. Although isolation of ST78 strains was clustered in a 14-months period suggesting nosocomial transmission, these strains were subdivided into three clades by SNP analysis: clade A (n = 10), clade B (n = 1), clade C (n = 3). A part of clonal relatedness was unexpected by the epidemiological information at the time of isolation of the strains. Most of the IMP-producing ECC strains were susceptible to non-β-lactam antibiotics and had relatively low minimum inhibitory concentrations to carbapenems (≤4 μg/mL). Five of six infections caused by IMP-producing ECC were treated successfully.

CONCLUSIONS

Whole-genome sequencing analysis revealed the outbreak was caused by three different clades of ST78 strains, where patients had favorable treatment outcome of the infections compared with that caused by Enterobacterales producing other carbapenemases, possibly due to their non-multidrug-resistant phenotype.

摘要

背景

有关产IMP 型肠杆菌科细菌的临床和微生物学特征的信息有限。在这里,我们描述了涉及多个肠杆菌科序列型(ST)78 型 ECC 菌株克隆群的产 IMP 型阴沟肠杆菌复合群(ECC)的机构暴发。

方法

对四年研究期间分离的 18 株产 IMP 型 ECC 菌株进行了药敏试验、全基因组测序和接合实验。通过平均核苷酸同一性分析确定种和亚种,通过多位点序列分型和核心基因组单核苷酸多态性(SNP)分析分析分离株的克隆相关性。从病历中提取相关临床信息。

结果

18 株产 IMP 型 ECC 分离株中有 14 株被确定为阴沟肠杆菌 ST78。16 株分离株,包括 13 株属于 ST78 的分离株,携带 bla 在 In316 样 1 类整合子中,并且还携带 IncHI2 质粒。携带 bla 的 12 株携带 IncHI2 质粒的分离株和携带 bla 的 1 株携带 IncL/M 质粒的分离株的接合实验均成功。尽管携带 ST78 菌株的分离株在 14 个月的时间内呈簇状,提示存在医院内传播,但这些菌株通过 SNP 分析分为三个克隆群:A 群(n = 10)、B 群(n = 1)、C 群(n = 3)。部分克隆相关性与菌株分离时的流行病学信息不符。大多数产 IMP 型 ECC 分离株对非β-内酰胺类抗生素敏感,对碳青霉烯类的最低抑菌浓度相对较低(≤4μg/ml)。6 例产 IMP 型 ECC 感染中有 5 例成功治疗。

结论

全基因组测序分析显示,此次暴发是由三个不同的 ST78 菌株克隆群引起的,与产生其他碳青霉烯酶的肠杆菌科细菌引起的感染相比,患者的感染治疗结果较好,可能是由于其非多重耐药表型所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1b0/7983292/4021e0fd5476/12879_2021_5952_Fig1_HTML.jpg

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