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

Kazumi Takehana,Keito Ida,Brian Hayama,Kyoji Moriya,Kotaro Aoki,Yoshikazu Ishii,Daigo Shoji,Tomomi Akatsuchi,Sohei Harada,Daisuke Ohkushi,Yohei Doi,Koh Okamoto

doi:10.1186/s12879-021-05952-9

Abstract

BackgroundInformation 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.MethodsAntimicrobial 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.ResultsFourteen of 18 IMP-producing ECC isolates were determined as Enterobacter hormaechei ST78. Sixteen isolates, including 13 isolates belonging to ST78, carried blaIMP-1 in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carrying blaIMP-1 on IncHI2 plasmids and for an isolate carrying blaIMP-11 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.ConclusionsWhole-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.

Highlights

Information about the clinical and microbiological characteristics of IMP-producing Enterobacterales has been limited
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
All six patients from whom Carbapenemase-producing Enterobacterales (CPE) was isolated within 3 days after surgery (Patient-2, − 5, − 10, − 14, − 15, and − 16) received routine airway nebulization and frequent airway suctioning at intensive care unit (ICU) and bronchoscopy was performed at operating rooms in two patients (Patient 5 and − 15)

Summary

Introduction

Information about the clinical and microbiological characteristics of IMP-producing Enterobacterales has been limited. We describe an institutional outbreak of IMP-producing Enterobacter cloacae complex (ECC) involving multiple clades of ECC sequence type (ST) 78 strains. Carbapenem-resistant Enterobacterales (CRE) has been spreading globally during the last decade and acknowledged as an imminent risk for public health due to the limited treatment options for the infections caused by the organisms [1]. A national surveillance conducted by National Institute of Infectious Diseases reported that resistance rates to meropenem of Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex (ECC) in 2018 were 0.1, 0.5, and 1.1%, respectively (https://janis.mhlw.go.jp/ english/report/open_report/2018/3/1/ken_Open_ Report_Eng_201800_clsi2012.pdf). IMP enzymes have been overwhelmingly dominant among carbapenemases produced by Enterobacterales in Japan, major species of CPE is different in each geographic area in Japan. While IMP-producing ECC is most common in Tokyo, IMP-producing K. pneumoniae and E. coli are more common around Osaka [5, 6]

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