The global epidemiology of carbapenemase-producing Enterobacteriaceae.
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ABSTRACT:
SUBMITTER: van Duin D
PROVIDER: S-EPMC5477705 | biostudies-other | 2017 May
REPOSITORIES: biostudies-other
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Project description:Carbapenemase-producing Enterobacteriaceae (CPE) were almost nonexistent up to the 1990s, but are today encountered routinely in hospitals and other healthcare facilities in many countries including the United States. KPC-producing Klebsiella pneumoniae was the first to emerge and spread globally and is endemic in the United States, Israel, Greece, and Italy. Recently, NDM-producing Enterobacteriaceae and OXA-48-producing K. pneumoniae appear to be disseminating from South Asia and Northern Africa, respectively. They are almost always resistant to all β-lactams including carbapenems and many other classes. Mortality from invasive CPE infections reaches up to 40%. To obtain the maximal benefit from the limited options available, dosing of antimicrobial agents should be optimized based on pharmacokinetic data, especially for colistin and carbapenems. In addition, multiple observational studies have associated combination antimicrobial therapy with lower mortality compared with monotherapy for these infections. The outcomes appear to be especially favorable when patients are treated with a carbapenem and a second agent such as colistin, tigecycline, and gentamicin, but the best approach is yet to be defined.
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Project description:In Portugal, the epidemiological stage for the spread of carbapenemase-producing Enterobacteriaceae (CPE) increased from sporadic isolates or single hospital clones (2010-2013), to hospital outbreaks, later. Here we report data from a 6-month study performed under the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE). During the study period, 67 isolates (61 Klebsiella pneumoniae and 6 Escherichia coli) non-susceptible to carbapenems were identified in participant hospital laboratories. We detected 37 bla KPC-type (including one new variant: bla KPC-21), 1 bla GES-5, and 1 bla GES-6 plus bla KPC-3, alone or in combination with other bla genes. Bioinformatics analysis of the KPC-21-producing E. coli identified the new variant bla KPC-21 in a 12,748 bp length plasmid. The bla KPC-21 gene was harbored on a non-Tn4401 element, presenting upstream a partial ISKpn6 (?ISKpn6/?traN) with the related left IR (IRL) and downstream a truncated Tn3 transposon. PFGE and MLST analysis showed an important diversity, as isolates belonged to distinct PFGE and STs profiles. In this study, we highlighted the presence of the high-risk clone E. coli sequence-type (ST) 131 clade C/H30. This worldwide disseminated E. coli lineage was already detected in Portugal among other antibiotic resistance reservoirs. This study highlights the intra- and inter-hospital spread and possible intercontinental circulation of CPE isolates.
| S-EPMC6277554 | biostudies-literature
Project description:International data on the molecular epidemiology of Enterobacteriaceae with IMP carbapenemases are lacking. We performed short-read (Illumina) whole-genome sequencing on a global collection of 38 IMP-producing clinical Enterobacteriaceae (2008 to 2014). IMP-producing Enterobacteriaceae (7 varieties within 11 class 1 integrons) were mainly present in the South Pacific and Asia. Specific blaIMP-containing integrons (In809 with blaIMP-4, In722 with blaIMP-6, and In687 with blaIMP-14) were circulating among different bacteria in countries such as Australia, Japan, and Thailand. In1312 with blaIMP-1 was present in Klebsiella pneumoniae from Japan and Citrobacter freundii from Brazil. Klebsiella pneumoniae (n = 22) was the most common species; clonal complex 14 (CC14) from Philippines and Japan was the most common clone and contained In1310 with blaIMP-26 and In1321 with blaIMP-6 The Enterobacter cloacae complex (n = 9) consisted of Enterobacter hormaechei and E. cloacae cluster III. CC78 (from Taiwan) containing In73 with blaIMP-8 was the most common clone among the E. cloacae complex. This study highlights the importance of surveillance programs using the latest molecular techniques for providing insight into the characteristics and global distribution of Enterobacteriaceae with blaIMP genes.
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Project description:BackgroundInternational data on the molecular epidemiology of Enterobacteriaceae with VIM carbapenemases are limited.MethodsWe performed short read (Illumina) WGS on a global collection of 89 VIM-producing clinical Enterobacteriaceae (2008-14).ResultsVIM-producing (11 varieties within 21 different integrons) isolates were mostly obtained from Europe. Certain integrons with bla VIM were specific to a country in different species and clonal complexes (CCs) (In 87 , In 624 , In 916 and In 1323 ), while others had spread globally among various Enterobacteriaceae species (In 110 and In 1209 ). Klebsiella pneumoniae was the most common species ( n = 45); CC147 from Greece was the most prevalent clone and contained In 590 -like integrons with four different bla VIM s. Enterobacter cloacae complex was the second most common species and mainly consisted of Enterobacter hormaechei ( Enterobacter xiangfangensis , subsp. steigerwaltii and Hoffmann cluster III). CC200 (from Croatia and Turkey), CC114 (Croatia, Greece, Italy and the USA) and CC78 (from Greece, Italy and Spain) containing bla VIM-1 were the most common clones among the E. cloacae complex.ConclusionsThis study highlights the importance of surveillance programmes using the latest molecular techniques in providing insight into the characteristics and global distribution of Enterobacteriaceae with bla VIM s.
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Project description:Carbapenemase-producing Enterobacteriaceae isolated from Hong Kong, China
| PRJNA595034 | ENA
Project description:We performed whole-genome sequencing on 170 clinical carbapenemase-producing Enterobacter spp. isolates collected globally during 2008-2014. The most common carbapenemase was VIM, followed by New Delhi metallo-β-lactamase (NDM), Klebsiella pneumoniae carbapenemase, oxacillin 48, and IMP. The isolates were of predominantly 2 species (E. xiangfangensis and E. hormaechei subsp. steigerwaltii) and 4 global clones (sequence type [ST] 114, ST93, ST90, and ST78) with different clades within ST114 and ST90. Particular genetic structures surrounding carbapenemase genes were circulating locally in various institutions within the same or between different STs in Greece, Guatemala, Italy, Spain, Serbia, and Vietnam. We found a common NDM genetic structure (NDM-GE-U.S.), previously described on pNDM-U.S. from Klebsiella pneumoniae ATCC BAA-214, in 14 different clones obtained from 6 countries spanning 4 continents. Our study highlights the importance of surveillance programs using whole-genome sequencing in providing insight into the molecular epidemiology of carbapenemase-producing Enterobacter spp.
| S-EPMC6004858 | biostudies-literature
Project description:Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.
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Project description:The dissemination of carbapenem resistance in Escherichia coli has major implications for the management of common infections. bla KPC, encoding a transmissible carbapenemase (KPC), has historically largely been associated with Klebsiella pneumoniae, a predominant plasmid (pKpQIL), and a specific transposable element (Tn4401, ~10 kb). Here we characterize the genetic features of bla KPC emergence in global E. coli, 2008-2013, using both long- and short-read whole-genome sequencing. Amongst 43/45 successfully sequenced bla KPC-E. coli strains, we identified substantial strain diversity (n = 21 sequence types, 18% of annotated genes in the core genome); substantial plasmid diversity (≥9 replicon types); and substantial bla KPC-associated, mobile genetic element (MGE) diversity (50% not within complete Tn4401 elements). We also found evidence of inter-species, regional and international plasmid spread. In several cases bla KPC was found on high copy number, small Col-like plasmids, previously associated with horizontal transmission of resistance genes in the absence of antimicrobial selection pressures. E. coli is a common human pathogen, but also a commensal in multiple environmental and animal reservoirs, and easily transmissible. The association of bla KPC with a range of MGEs previously linked to the successful spread of widely endemic resistance mechanisms (e.g. bla TEM, bla CTX-M) suggests that it may become similarly prevalent.
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Project description:We report the epidemiological impact of carbapenemase-producing Enterobacteriaceae (CPE) in Spain in 2012. Of the 237 carbapenemases detected, 163 were from the OXA-48 group, 60 were from VIM-1, 8 were from KPC-2, 5 were from IMP, and 1 was from NDM-1. Interhospital spread of carbapenemase-producing Klebsiella pneumoniae was due to a limited number of multilocus sequence types (MLST) and carbapenemase types, including ST15-VIM-1, ST11-OXA-48, ST405-OXA-48, ST101-KPC-2, and ST11-VIM-1. The number of CPE cases in Spain has increased sharply in recent years, due mainly to the emergence of OXA-48.
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Project description:The emergence of carbapenem resistance is a significant public health concern. The rate of infections caused by carbapenemase-producing Citrobacter spp., particularly C. freundii, is increasing. Concomitantly, comprehensive global genomic data on carbapenemase-producing Citrobacter spp. are scarce. We used short read whole-genome sequencing to describe the molecular epidemiology and international distribution of eighty-six carbapenemase-producing Citrobacter spp. obtained from two surveillance programs (2015 to 17). The common carbapenemases were KPC-2 (26%), VIM-1 (17%), IMP-4 (14%) and NDM-1 (10%). C. freundii and C. portucalensis were the principal species. C. freundii consisted of multiple clones obtained mainly from Colombia (with KPC-2), the United States (with KPC-2, -3), and Italy (with VIM-1). Two dominant C. freundii clones were identified: ST98 was linked with blaIMP-8 from Taiwan and blaKPC-2 from the United States, and ST22 was linked with blaKPC-2 from Colombia and blaVIM-1 from Italy. C. portucalensis consisted mainly of two clones: ST493 with blaIMP-4 which was limited to Australia, and ST545 with blaVIM-31 which was limited to Turkey. Class I integron (In916) with blaVIM-1 was circulating between multiple sequence types (STs) in Italy, Poland, and Portugal. In73 with blaIMP-8 was circulating between various STs in Taiwan, while In809 with blaIMP-4 was circulating between different STs in Australia. The global carbapenemase-producing Citrobacter spp. population is dominated by diverse STs with different characteristics and varied geographical distribution and thus requires continued monitoring. Ongoing genomic surveillance should use methodologies able to distinguish between C. freundii and C. portucalensis. IMPORTANCE Citrobacter spp. are gaining recognition as important causes of hospital-acquired infections in humans. Among Citrobacter spp., carbapenemase-producing strains are cause of utmost concern to health care services globally due to their ability to resist therapy with virtually any beta-lactam antibiotic. Here, we described the molecular characteristics of a global collection of carbapenemase-producing Citrobacter spp. C. freundii and C. portucalensis were the most common species among Citrobacter spp. with carbapenemases from this survey. Importantly, C. portucalensis was misidentified as C. freundii when using Vitek 2.0/MALDI-TOF MS (matrix-assisted laser desorption/ionization-time of flight mass spectrometry) phenotypic identification, which has important implications for future surveys. Among C. freundii, we identified two dominant clones: ST98 with blaIMP-8 from Taiwan and blaKPC-2 from the United States, and ST22 with blaKPC-2 from Colombia and blaVIM-1 from Italy. As for C. portucalensis, the dominant clones consisted of ST493 with blaIMP-4 from Australia and ST545 with blaVIM-31 from Turkey.
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