Characterization of carbapenemase-producing Enterobacteriaceae from colonized patients in a university hospital in Madrid, Spain, during the R-GNOSIS project depicts increased clonal diversity over time with maintenance of high-risk clones

Hernández-García, Marta; Pérez-Viso, Blanca; Turrientes, María-Carmen; Díaz-Agero, Cristina; López‐Fresneña, Nieves; Bonten, Marc J. M.; Malhotra-Kumar, Surbhi; Ruíz-Garbajosa, Patricia; Cantón, Rafael

doi:10.1093/jac/dky284

Cited by 54 publications

(61 citation statements)

References 19 publications

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“…During the study period, the incidence of CPE colonization in our institution was 2%, and it was due to mainly the success and persistence of OXA-48-producing K. pneumoniae clones, particularly the sequence type 11 (ST11) high-risk clone (34). Similar results have been reported in other Spanish hospitals (35)(36)(37).…”

Section: Discussionsupporting

confidence: 84%

First Report of an OXA-48- and CTX-M-213-Producing Kluyvera Species Clone Recovered from Patients Admitted in a University Hospital in Madrid, Spain

Hernández-García

León‐Sampedro

Pérez-Viso

et al. 2018

Antimicrob Agents Chemother

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species other than also contribute to OXA-48 carbapenemase endemicity. We studied the emergence of an OXA-48-producing species clone, which expresses the novel CTX-M-213 enzyme, colonizing patients in our hospital. Rectal swabs from patients admitted in four wards (March 2014 to March 2016; R-GNOSIS project) were seeded onto Chromo ID-ESBL) and Chrom-CARB/OXA-48 chromogenic agar plates. Carbapenemases and extended-spectrum β-lactamases (ESBLs) were characterized (PCR, sequencing, cloning, and site-directed mutagenesis), and antibiotic susceptibility was determined. Clonal relatedness was established (XbaI pulsed-field gel electrophoresis [XbaI-PFGE]), and plasmid content was studied (transformation, S1 nuclease digestion-PFGE, SB-hybridization, restriction fragment length polymorphism [RFLP] analysis [DraI and HpaI], and PCR [incompatibility group and A,U, and A genes]). Whole-genome sequencing (WGS) (Illumina HiSeq-2500) and further bioinformatics analysis of plasmids (PLACNET and plasmidSPAdes) were performed. Patients' charts were reviewed. Six unrelated patients (median age, 75 years [range, 59 to 81 years]; 4/6 male patients) colonized with OXA-48-producing species isolates (>95% similarity of the PFGE pattern) were identified. Nosocomial acquisition was demonstrated. In two patients, OXA-48-producing species isolates coexisted with OXA-48-producing, , and The gene was located on an ∼60-kb IncL plasmid related to IncL/M-pOXA-48a and the novel gene in a conserved chromosomal region of species isolates. CTX-M-213, different from CTX-M-13 (K56E) but conferring a similar β-lactam resistance profile, was identified. Genomic analysis also revealed a 177-kb IncF plasmid (class I integron harboring and) and an 8-kb IncQ plasmid (IS- ). We describe the first plasmid in spp. and the novel chromosomal CTX-M-213 enzyme and highlight further nosocomial dissemination of through clonal lineages or plasmids related to IncL/M-pOXA-48a.

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Section: Discussionsupporting

confidence: 84%

First Report of an OXA-48- and CTX-M-213-Producing Kluyvera Species Clone Recovered from Patients Admitted in a University Hospital in Madrid, Spain

Hernández-García

León‐Sampedro

Pérez-Viso

et al. 2018

Antimicrob Agents Chemother

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“…The study enrolled all patients admitted to two medical wards (gastroenterology and pneumology) and two surgical wards (neurosurgery and urology) in the hospital. The full details of the R-GNOSIS study in our hospital, including the study population and CPE characterization, have been previously reported by Hernandez-Garcia et al 18,23 . Briefly, from March 2014 to March 2016, 28,089 rectal swabs were collected from 9,275 patients, and 171 pOXA-48-carrying enterobacteria strains were isolated and characterised from 105 patients (Figure 1, Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…We studied samples collected from patients admitted in a Spanish university hospital from March 4th, 2014, to March 31 st , 2016, as part of an active surveillance-screening program for detecting ESBL/carbapenemase-carriers (R-GNOSIS-FP7-HEALTH-F3-2011-282512, www.r-gnosis.eu/) 18,22,23,36 . This study was approved by the Ramón y Cajal University Hospital Ethics Committee (Reference 251/13), which waived the need for informed consent from patients on the basis that the study was assessing ward-level effects and it was of minimal risk.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were initially characterised as previously described, following the RGNOSIS protocol 23 . Briefly, swabs were plated on Chromo ID-ESBL and Chrom-CARB/OXA-48 selective agar media (BioMérieux, France) and bacterial colonies able to grow on these media were identified by MALDI-TOF MS (Bruker Daltonics, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…In the present study, we examined the between-patient and within-patient transfer dynamics of plasmid pOXA-48 in a tertiary hospital over a two-year period. For our analysis, we used a large and well-characterized collection of pOXA-48-carrying enterobacteria generated at the Hospital Universitario Ramon y Cajal in Madrid as part of the European project R-GNOSIS (Resistance of Gram-Negative Organisms: Studying Intervention Strategies) 22,23 . Using statistical models and combining epidemiological data from more than 9,000 patients with whole-genome sequence information from 250 enterobacteria clones, we aimed to define pOXA-48 transfer dynamics at an unprecedented resolution.…”

Section: Introductionmentioning

confidence: 99%

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Dissemination routes of the carbapenem resistance plasmid pOXA-48 in a hospital setting

León‐Sampedro

DelaFuente

Díaz-Agero

et al. 2020

Preprint

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Introductory paragraph 28 Infections caused by carbapenemase-producing enterobacteria (CPE) are a major 29 concern in clinical settings worldwide. Two fundamentally different processes shape 30 the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to 31 patient (between-patient transfer), and the transfer of carbapenemase-encoding 32 plasmids between enterobacteria in the gut microbiota of individual patients (within-33 patient transfer). The relative contribution of each process to the overall dissemination 34 of carbapenem resistance in hospitals remains poorly understood. Here, we used 35 mechanistic models combining epidemiological data from more than 9,000 patients 36 with whole genome sequence information from 250 enterobacteria clones to 37 characterise the dissemination routes of the carbapenemase-encoding plasmid pOXA-38 48 in a hospital setting over a two-year period. Our results revealed frequent between-39 patient transmission of high-risk pOXA-48-carrying clones, mostly of Klebsiella 40 pneumoniae and sporadically Escherichia coli. The results also identified pOXA-48 41 dissemination hotspots within the hospital, such as specific wards and individual rooms 42 within wards. Using high-resolution plasmid sequence analysis, we uncovered the 43 pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid 44 transfer occurs in the gut of virtually every colonised patient. The complex and 45 multifaceted epidemiological scenario exposed by this study provides new insights for 46 the development of intervention strategies to control the in-hospital spread of CPE. 47 48 frequency with which this occurs in the clinical settings and its importance for the 56 dissemination of resistance at a local level remain poorly defined. 57 One of the most clinically relevant groups of nosocomial pathogens are enterobacteria 58 that produce carbapenemases (ß-lactamase enzymes able to degrade carbapenem 59 antibiotics). Among carbapenemase-producing enterobacteria (CPE), clones of 60 Klebsiella pneumoniae and Escherichia coli carrying plasmid-encoded 61 carbapenemases pose the highest clinical threat 5 . Despite their clinical relevance, 62 major gaps remain in our understanding of the epidemiology of CPE and of 63 carbapenemase-encoding plasmids. Previous work has highlighted the importance of 64 in-hospital CPE transmission from patient to patient 6,7 (between-patient transfer). 65 However, the dissemination and evolution of CPE in hospitals present an additional 66 layer of complexity: the transfer of carbapenemase-encoding plasmids between 67 enterobacteria clones in the gut microbiota of individual patients (within-patient 68 transfer) 8,9 . Understanding the relative importance of between-patient and within-69 patient transfer is of central importance for understanding the epidemiology of CPE 70 and informing intervention strategies to control the spread of carbapenem resistance 71 in clinical settings. 72One of the most frequent carbapenemases in enterobacteria is O...

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NDM-5-carrying Klebsiella pneumoniae ST437 belonging to high-risk clonal complex (CC11) from an urban river in eastern India

Sahoo

Dixit

et al. 2023

3 Biotech

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Characterization of carbapenemase-producing Enterobacteriaceae from colonized patients in a university hospital in Madrid, Spain, during the R-GNOSIS project depicts increased clonal diversity over time with maintenance of high-risk clones

Abstract: We describe a polyclonal and changeable CPE population over time. Coexistence of worldwide disseminated clones, such as ST11-OXA-48- K. pneumoniae, with unrelated and emerging OXA-48-E. coli clones, depicts a disturbing CPE epidemiology in our institution.

Cited by 54 publications

References 19 publications

First Report of an OXA-48- and CTX-M-213-Producing Kluyvera Species Clone Recovered from Patients Admitted in a University Hospital in Madrid, Spain

First Report of an OXA-48- and CTX-M-213-Producing Kluyvera Species Clone Recovered from Patients Admitted in a University Hospital in Madrid, Spain

Dissemination routes of the carbapenem resistance plasmid pOXA-48 in a hospital setting

NDM-5-carrying Klebsiella pneumoniae ST437 belonging to high-risk clonal complex (CC11) from an urban river in eastern India

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