Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei

Roberts, Leah W.; Harris, Patrick N A; Forde, Brian M.; Zakour, Nouri L. Ben; Catchpoole, Elizabeth; Stanton-Cook, Mitchell; Phan, Minh-Duy; Sidjabat, Hanna E.; Bergh, Haakon; Heney, Claire; Gawthorne, Jayde A.; Lipman, Jeffrey; Allworth, Anthony; Chan, Kok‐Gan; Chong, Teik Min; Yin, Wai‐Fong; Schembri, Mark A.; Paterson, David L.; Beatson, Scott A.

doi:10.1038/s41467-019-14139-5

Cited by 42 publications

(55 citation statements)

References 69 publications

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“…Carbapenems are considered the drug of choice in treating such infections. However, the increased usage of these antibiotics has led to the emergence of carbapenem-resistant strains ( Roberts et al, 2020 ). Center for Disease Control (CDC) considers carbapenem-resistant Enterobacterales (CRE) as a serious global threat to patient health that limits treatment options, especially in chronically ill patients in intensive care units (ICU) and long-term care facilities ( McConville et al, 2017 ; Gupta et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic Plurality of OXA/NDM-Encoding Features Characterized From Enterobacterales Recovered From Czech Hospitals

et al. 2021

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The aim of this study was to characterize four Enterobacterales co-producing NDM- and OXA-48-like carbapenemases from Czech patients with travel history or/and previous hospitalization abroad. Klebsiella pneumoniae isolates belonged to “high risk” clones ST147, ST11, and ST15, while the Escherichia coli isolate was assigned to ST167. All isolates expressed resistance against most β-lactams, including carbapenems, while retaining susceptibility to colistin. Furthermore, analysis of WGS data showed that all four isolates co-produced OXA-48- and NDM-type carbapenemases, in different combinations (Kpn47733: blaNDM–5 + blaOXA–181; Kpn50595: blaNDM–1 + blaOXA–181; Kpn51015: blaNDM–1 + blaOXA–244; Eco52418: blaNDM–5 + blaOXA–244). In Kpn51015, the blaOXA–244 was found on plasmid p51015_OXA-244, while the respective gene was localized in the chromosomal contig of E. coli Eco52418. On the other hand, blaOXA–181 was identified on a ColKP3 plasmid in isolate Kpn47733, while a blaOXA–181-carrying plasmid being an IncX3-ColKP3 fusion was identified in Kpn50595. The blaNDM–1 gene was found on two different plasmids, p51015_NDM-1 belonging to a novel IncH plasmid group and p51015_NDM-1 being an IncFK1-FIB replicon. Furthermore, the blaNDM–5 was found in two IncFII plasmids exhibiting limited nucleotide similarity to each other. In both plasmids, the genetic environment of blaNDM–5 was identical. Finally, in all four carbapenemase-producing isolates, a diverse number of additional replicons, some of these associated with important resistance determinants, like blaCTX–M–15, arr-2 and ermB, were identified. In conclusion, this study reports the first description of OXA-244-producing Enterobacterales isolated from Czech hospitals. Additionally, our findings indicated the genetic plurality involved in the acquisition and dissemination of determinants encoding OXA/NDM carbapenemases.

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Section: Introductionmentioning

confidence: 99%

Genetic Plurality of OXA/NDM-Encoding Features Characterized From Enterobacterales Recovered From Czech Hospitals

et al. 2021

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“…Resistance to carbapenems in Enterobacteriaceae occurs via one or a combination of carbapenemase production, production of ESBLs and/or AmpC in combination with porin loss/deficiency, carbapenem efflux, or mutations in penicillin-binding proteins (PBPs) [6,7], among which carbapenemase gene acquisition is of greatest concern [8], as it most frequently occurs via transfer of plasmids, which usually co-harbor β-lactamases and other resistance determinants, rendering these carbapenemase-producing Enterobacteriaceae (CPE) strains multi-drug resistant (MDR) or extensively drug-resistant (XDR) [9]. CPE is the most problematic due to higher-level antimicrobial resistance, clonal spread and horizontal gene transfer [10].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

Jin

et al. 2020

Antimicrob Resist Infect Control

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Background Nosocomial carbapenemase-producing Enterobacterieceae (CPE) infections constitute a major global health concern and are associated with increased morbidity and mortality. Rectal colonization with CPE is a risk factor for bacterial translocation leading to subsequent endogenous CPE infections. This prospective observational study was aimed to investigate the prevalence and epidemiology of rectal colonization of CPE, the carbapenemase genotypes, and to identify the independent risk factors for the acquisition of CPE colonization in high-risk patients from ICU and HSCT wards in a university hospital in China. Methods In a prospective cohort study, 150 fecal samples from rectal swabs were consecutively obtained for inpatients from the intensive care unit (ICU) and hematopoietic stem cell transplantation (HSCT) wards from November 2018 to May 2019, and screening test for CPE was conducted by using prepared in-house trypsin soybean broth (TSB) selective media and MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and carbapenemase genes were characterized by both the GeneXpert Carba-R and PCR for blaKPC, blaNDM, blaIMP, blaVIM and blaOXA. Multi-locus sequence typing (MLST) was employed to characterize the genetic relationships among the carbapenemase-producing K. Pneumonia (CPKP) isolates. In order to further investigate the risk factors and clinical outcomes of CPE colonization, a prospective case-control study was also performed. Results Twenty-six suspected CPE strains, including 17 Klebsiella pneumoniae, 6 Escherichia coli, 1 Citrobacter freundii, 1 Enterobacter Kobe, and 1 Raoultella ornithinolytica, were identified in 25 non-duplicated rectal swab samples from 25 patients, with a carriage rate of 16.67% (25/150). Through GeneXpert Carba-R and subsequent PCR and sequencing, all the suspected CPE isolates were identified to be positive for the carbapenemase genes, of which 17 were blaKPC-carriers, and another 9 were blaNDM-producers. MLST designated all the CPKP isolates to be ST11 clone. Multivariate analysis indicated that urinary system diseases, operation of bronchoscopy, and combined use of antibiotics were independent risk factors for acquiring CPE colonization in high-risk patients from the ICU and HSCT wards. Conclusions This study revealed a high prevalence of rectal CPE colonization in high-risk patients from ICU and HSCT wards, and a predominant colonization of the KPC-producing K. pneumoniae clone ST11. Stricter infection control measures are urgently needed to limit the dissemination of CPE strains, especially in patients who were afflicted by urinary system diseases, have underwent bronchoscopy, and were previously exposed to combined antibiotic use.

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“…Resistance to carbapenems in Enterobacteriaceae occurs via one or a combination of the following four mechanisms: carbapenemase production, production of ESBLs and/or AmpC in combination with porin loss/deficiency, carbapenem efflux, or mutations in penicillin-binding proteins (PBPs) [6,7], among which carbapenemase gene acquisition is of greatest concern [8], as it most frequently occurs via transfer of plasmids, which usually co-harbor β-lactamases and other resistance determinants, rendering these carbapenemase-producing Enterobacteriaceae (CPE) strains multi-drug resistance (MDR) or extensively drug-resistant (XDR) [9]. CPE is the most problematic owing to higher-level antimicrobial resistance, clonal spread and horizontal gene transfer [10].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

Sun

et al. 2020

Preprint

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Background: Nosocomial infections caused by carbapenemase-producing Enterobacterieceae (CPE) constitute a major global health concern and are associated with increased morbidity and mortality. Rectal colonization with CPE is a risk factor for bacterial translocation leading to subsequent endogenous CPE infections. This prospective observational study was aimed to investigate the prevalence and epidemiology of rectal colonization of CPE, the carbapenemase genotypes, and to identify the independent risk factors for the acquisition of CPE colonization in high-risk patients from ICU and HSCT wards in a university hospital in China. Methods: In a prospective cohort study, 150 fecal samples from rectal swabs were consecutively obtained for inpatients from the ICU and HSCT wards from November 2018 to May 2019, and screening test for CPE was conducted by using home-made trypsin soybean broth (TSB) selective media and MacConkey agar. Antimicrobial susceptibility was determined by the broth microdilution method and carbapenemase genes were characterized by both the GeneXpert Carba-R and PCR for blaKPC, blaNDM, blaIMP, blaVIM and blaOXA. In order to further investigate the risk factors and clinical outcomes of CPE colonization, a prospective case-control study was also performed.Results: 26 suspected CPE strains, including 17 Klebsiella pneumoniae, 6 Escherichia coli, 1 Citrobacter freundii, 1 Enterobacter Kobe, and 1 Raoultella ornithinolytica, were identified in 25 non-duplicated fecal samples from 25 patients, with a carriage rate of 16.67% (25/150). Through GeneXpert Carba-R and subsequent PCR and sequencing, all the suspected CPE isolates were identified to be positive for the carbapenemase genes, of which 17 were blaKPC-carriers, and another 9 were blaNDM-producers. Multivariate analysis indicated that urinary system diseases, operation of bronchoscopy, and combined use of antibiotics were independent risk factors for acquiring CPE colonization in high-risk patients from the ICU and HSCT wards. Conclusions: This study revealed a high prevalence of rectal CPE colonization in high-risk patients from ICU and HSCT wards, and a predominant colonization of the KPC-producing K. pneumoniae strains. Stricter infection control measures are urgently needed to limit the dissemination of CPE strains, especially in patients who were afflicted by urinary system diseases, have underwent bronchoscopy, and were previously exposed to combined antibiotic use.

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Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei

Cited by 42 publications

References 69 publications

Genetic Plurality of OXA/NDM-Encoding Features Characterized From Enterobacterales Recovered From Czech Hospitals

Genetic Plurality of OXA/NDM-Encoding Features Characterized From Enterobacterales Recovered From Czech Hospitals

Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

Epidemiology and risk factors of rectal colonization of carbapenemase-producing Enterobacteriaceae among high-risk patients from ICU and HSCT wards in a university hospital

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