The Global Ascendency of OXA-48-Type Carbapenemases

Pitout, Johann; Peirano, Gisele; Kock, Marleen M.; Strydom, Kathy-Anne; Matsumura, Yasufumi

doi:10.1128/cmr.00102-19

Cited by 320 publications

(379 citation statements)

References 300 publications

(500 reference statements)

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“…In line with previous reports 10 , K. pneumoniae was the most frequent pOXA-48-carrying species (n= 108). However, pOXA-48 was detected in an additional 7 enterobacterial species, with E. coli being the second most frequent carrier (n= 45, Figure 1D, Table S1).…”

Section: Resultssupporting

confidence: 92%

“…One of the most frequent carbapenemases in enterobacteria is OXA-48 10 . OXA-48 was first described in a K. pneumoniae strain isolated in Turkey in 2001 11 and is now distributed worldwide, with particularly high prevalence in North Africa, Middle Eastern countries, and Europe 10 . The bla oχA-48 gene is usually encoded in an IncL, broad-host-range conjugative plasmid called pOXA-48 8 (Figure S1).…”

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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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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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“…Spread of CPE has been increasingly reported worldwide since first description more than 20 years ago, with predominance of metallo-beta-lactamase (MBL) producers in Asia and Europe, KPC producers in the United States, and OXA-48 producers in the Mediterranean countries (6,9,21,22). These carbapenemases have been increasingly recovered in Spain, and OXA-48 isolates are currently the most prevalent ones (3,6).…”

Section: Discussionmentioning

confidence: 99%

“…The OXA-48 carbapenemase was first identified in 2003 from a Klebsiella pneumoniae clinical isolate recovered in Turkey (7). Since then, OXA-48 producers have increasingly been detected worldwide but particularly in Europe (8,9). This enzyme weakly hydrolyses carbapenems and spares extended-spectrum cephalosporins (10).…”

mentioning

confidence: 99%

Early OXA-48-Producing Enterobacterales Isolates Recovered in a Spanish Hospital Reveal a Complex Introduction Dominated by Sequence Type 11 (ST11) and ST405 Klebsiella pneumoniae Clones

Gijón

Tedim

Valverde

et al. 2020

mSphere

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Carbapenemase-producing Enterobacterales (CPE) have become an important public health concern. In our hospital, VIM enzymes were first detected in 2005, Klebsiella pneumoniae carbapenemase (KPC) enzymes in 2009, and OXA-48 enzymes in 2012. We assess the population biology of the first OXA-48-producing Enterobacterales isolates recovered in our hospital (2012 to 2013) where infections by other carbapenemases had been endemic for several years. Over a 21-month period, 71 isolates (61 Klebsiella pneumoniae, 5 Escherichia coli, 2 Klebsiella aerogenes, and 1 each of Enterobacter cloacae, Klebsiella oxytoca, and Citrobacter amalonaticus) recovered from clinical and surveillance specimens from 57 patients (22.8% nonhospitalized) were investigated for OXA-48-like-producing enzymes. Analyses for characterization and determination of the location of the blaOXA-48 gene, plasmid transferability, sequence, and clonal relatedness were performed. Most of the isolates also coproduced CTX-M-15 (57/71, 80.3%) and/or VIM-1 (7/71, 9.8%). K. pneumoniae was predominantly identified as sequence type 11 (ST11) (63.4%) and ST405 (9.8%) and E. coli as ST540, ST1406, ST3163, and ST4301. The blaOXA-48 gene was part of Tn1999.2 located at the tir gene of plasmids (ca. ≥50 kb) of the IncL/M group, also carrying blaVIM-1 and blaCTX-M-15 genes. We selected one ST11 K. pneumoniae isolate for whole-genome sequencing in which we studied the plasmid containing the blaOXA-48 gene. This plasmid was compared with indexed plasmids existing in NCBI database by the use of BRIG and MAUVE. Our data suggest a rapid spread of blaOXA-48 genes between commonly isolated high-risk clones of Enterobacterales species, frequently associated with antibiotic resistance. Moreover, the emergence of the multiresistant ST11 K. pneumoniae clone among nonhospitalized patients emphasizes the difficulty of preventing its dissemination into the community. IMPORTANCE We present results of microbiological analysis of the first Enterobacterales isolates that were isolated in 2012 in our institution expressing OXA-48 carbapenemase. This enzyme confers resistance to carbapenems, an important group of antibiotics widely used in the hospitals. OXA-48 carbapenemase is currently present in many parts of the world, but it is found particularly frequently in the Mediterranean area. It was disseminated at the Ramón y Cajal Hospital and found to be associated with a particular Klebsiella pneumoniae strain, so-called high-risk clone ST11, which was previously found in our institution in association with other enzymes such as CTX-M-15, VIM-1, and KPC-3. This clone might have acquired a plasmid harboring the blaOXA-48 gene. Our results point out the importance of local epidemiology in the dissemination and maintenance of multidrug-resistant bacteria.

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“…Nowadays, several outbreaks have been registered in many South America countries, including Colombia [18], Argentina [19], and Brazil [20]. There are 11 allelic variants of OXA-48-like that have been described up to now [21]. The gene blaOXA-48 is located in 60-to 70-kb conjugative plasmids, generally associated with the transposon Tn1999 and its variants Tn1999.2 and Tn1999.3, and in the majority of the published data it has been associated with a nearby copy of IS1R [18,22,23].…”

Section: Introductionmentioning

confidence: 99%

OXA-48 Carbapenemase in Klebsiella pneumoniae Sequence Type 307 in Ecuador

et al. 2020

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Antibiotic resistance is on the rise, leading to an increase in morbidity and mortality due to infectious diseases. Klebsiella pneumoniae is a Gram-negative bacterium that causes bronchopneumonia, abscesses, urinary tract infection, osteomyelitis, and a wide variety of infections. The ubiquity of this microorganism confounds with the great increase in antibiotic resistance and have bred great concern worldwide. K. pneumoniae sequence type (ST) 307 is a widespread emerging clone associated with hospital-acquired infections, although sporadic community infections have also been reported. The aim of our study is to describe the first case of Klebsiella pneumoniae (ST) 307 harboring the blaOXA-48-like gene in Ecuador. We characterized a new plasmid that carry OXA-48 and could be the source of future outbreaks. The strain was recovered from a patient with cancer previously admitted in a Ukrainian hospital, suggesting that this mechanism of resistance could be imported. These findings highlight the importance of programs based on active molecular surveillance for the intercontinental spread of multidrug-resistant microorganisms with emergent carbapenemases.

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The Global Ascendency of OXA-48-Type Carbapenemases

Cited by 320 publications

References 300 publications

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

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

Early OXA-48-Producing Enterobacterales Isolates Recovered in a Spanish Hospital Reveal a Complex Introduction Dominated by Sequence Type 11 (ST11) and ST405 Klebsiella pneumoniae Clones

OXA-48 Carbapenemase in Klebsiella pneumoniae Sequence Type 307 in Ecuador

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