Molecular epidemiological analysis and risk factors for acquisition of carbapenemase-producing Enterobacter cloacae complex in a Japanese university hospital

Tetsuka, Nobuyuki; Hirabayashi, Aki; Matsumoto, Ayaka; Oka, Kazuki; Hara, Yuki; Morioka, Hiroshi; Iguchi, Mitsutaka; Tomita, Yoshihiko; Suzuki, Masato; Shibayama, Keigo; Yagi, Tetsuya

doi:10.1186/s13756-019-0578-3

Cited by 21 publications

(20 citation statements)

References 28 publications

(28 reference statements)

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“…Class 1-integron-harboring bla IMP-68 in pTMTA63632 (Fig. 1), which was assigned to In1702 in the INTEGRALL database (22), was similar to previously reported IMP genes harboring class 1 integrons, as the gene cassettes were located between intI1 and qacEΔ1-sul1 (10, 23, 24). Specifically, In1702 was compared with the class 1 integrons harbored by pNUH14_ECL028_1 and pIMP-A2015-49 plasmids previously found in Japan (24), which carried IMP-1 and IMP-11, respectively (Fig.…”

Section: Observationsupporting

confidence: 84%

IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

Kubota

Suzuki

Okuno

et al. 2019

mSphere

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IMP-type metallo-β-lactamases comprise one group of the “Big 5” carbapenemases. Here, a novel blaIMP-68 gene encoding IMP-68 (harboring a Ser262Gly point mutant of IMP-11) was discovered from meropenem-resistant but imipenem-susceptible Klebsiella pneumoniae TA6363. The Ser262Gly substitution was previously identified as important for substrate specificity according to a study of other IMP variants, including IMP-6. We confirmed that IMP-68 exhibited weaker imipenem-hydrolyzing activity than that for other carbapenems, demonstrating that the antimicrobial susceptibility profile of TA6363 originated from IMP-68 substrate specificity, with this likely to affect treatment strategies using antibacterial agents in clinical settings. Notably, the carbapenem resistance conferred by IMP-68 was undetectable based on the MIC of imipenem as a carbapenem representative, which demonstrates a comparable antimicrobial susceptibility profile to IMP-6-producing Enterobacteriaceae that previously spread in Japan due to lack of awareness of its existence.

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Section: Observationsupporting

confidence: 84%

IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

Kubota

Suzuki

Okuno

et al. 2019

mSphere

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“…1,2 During the last decade, the emergence of carbapenem-resistant Enterobacteriaceae (CRE), which led to limited treatment options, has become the main cause of clinical anti-infective treatment failure. 3,4 It is worth noting that carbapenem-resistant Enterobacter cloacae (CR-ECL), which is one of the most common species that has been focused on in studies of a single species of Enterobacterales, 5 has been reported in many countries such as Korea, the United States, India, and China. [6][7][8] Resistance to carbapenems is associated with several mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the identification of risk factors for CR-ECL infection would improve the choice and effcacy of empirical therapy. 5,7 Therefore, it is urgent to explore the epidemiological characteristics of CR-ECL infection.…”

Section: Introductionmentioning

confidence: 99%

<p>Carbapenem-Resistant <em>Enterobacter cloacae</em> Causing Nosocomial Infections in Southwestern China: Molecular Epidemiology, Risk Factors, and Predictors of Mortality</p>

Tian¹,

Huang²,

Yang³

et al. 2020

IDR

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Background: The emergence and spread of carbapenem-resistant Enterobacter cloacae (CR-ECL) have posed a serious threat to clinical management. This retrospective study assessed the epidemiological characteristics of CR-ECL to explore the risk factors and predictors of mortality in patients with CR-ECL infection. Methods: We performed a retrospective 1:2 case-control study of hospitalized patients from January 2014 to December 2017. A total of 85 consecutive unique CR-ECL strains comprised the case group, and 170 matched patients with carbapenem-susceptible Enterobacter cloacae (CS-ECL) infection at the same period as the control group. Isolates were screened for potential resistance genes by polymerase chain reaction (PCR) and molecular typing was performed by multilocus sequence typing (MLST). Results: The results of drug resistance gene detection showed that blaNDM-1 was the most common carbapenem resistance gene. The MLST results showed that ST51 was the predominant epidemic type, followed by ST88. ICU admission (P<0.001), drainage tube (P=0.002), central venous catheter (P=0.005), and carbapenem exposure (P=0.003) were independent risk factors for CR-ECL infection. Significant predictors for 28-day mortality included solid tumours (P=0.005), septic shock (P=0.019), and mechanical ventilation (P=0.027). Conclusion: Our study indicated that ST51 and ST88, which are closely related, were the predominant epidemic types of CR-ECL producing blaNDM-1 in southwestern China. Strengthening the surveillance of patients with solid tumours, septic shock and mechanical ventilation is an urgent need.

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“…Notably, two non-ST78 isolates (TUM17947 and TUM17948) carried bla IMP-1 on IncHI2 plasmids. Carriage of bla IMP-1 on IncHI2 plasmids by ECC isolates of multiple STs (e.g., ST53, 78, 113, 513, 1047) has been documented in another area (Nagoya) in Japan [23]. Although ST78 isolates appears to predominate among IMP-producing ECC isolates in Tokyo according to our previous study, the nationwide epidemiology remains to be elucidated [6].…”

Section: Discussionmentioning

confidence: 85%

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

Harada

Aoki

Ohkushi

et al. 2020

Preprint

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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. Twelve isolates, including 10 isolates belonging to ST78, carried blaIMP-1 in In316-like class 1 integron located on 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 16-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). Four of five 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.

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Molecular epidemiological analysis and risk factors for acquisition of carbapenemase-producing Enterobacter cloacae complex in a Japanese university hospital

Cited by 21 publications

References 28 publications

IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

<p>Carbapenem-Resistant <em>Enterobacter cloacae</em> Causing Nosocomial Infections in Southwestern China: Molecular Epidemiology, Risk Factors, and Predictors of Mortality</p>

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

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