Comparative Genomic Analysis of KPC-Encoding pKpQIL-Like Plasmids and Their Distribution in New Jersey and New York Hospitals

Chen, Liang; Chavda, Kalyan D.; Melano, Roberto G.; Jacobs, Michael; Koll, Brian; Hong, Tao; Rojtman, Albert; Levi, Michael H.; Bonomo, Robert A.; Kreiswirth, Barry N.

doi:10.1128/aac.00120-14

Cited by 96 publications

(103 citation statements)

References 33 publications

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“…Given that bla KPC is found on plasmids that are transmissible among Enterobacteriaceae and can produce novel CRKP strains (24,25) The heterogeneity in wzi types and bla KPC variants among ST258 isolates encountered in our study is consistent with emerging literature on variability in capsule types and associated resistance determinants in this ST (10,11,26). We found that bla was almost entirely restricted to wzi154-positive ST258 CRKP isolates, whereas bla KPC-2 was detected in isolates with several sequence and wzi alleles.…”

Section: Discussionsupporting

confidence: 79%

“…Although ST258 accounted for the majority of CRKP infections, we detected a larger proportion of non-ST258 strains, com- pared to previous reports from New York and elsewhere (2,11,24). Given that bla KPC is found on plasmids that are transmissible among Enterobacteriaceae and can produce novel CRKP strains (24,25) The heterogeneity in wzi types and bla KPC variants among ST258 isolates encountered in our study is consistent with emerging literature on variability in capsule types and associated resistance determinants in this ST (10,11,26).…”

Section: Discussionsupporting

confidence: 79%

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Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

et al. 2015

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bDespite the growing importance of carbapenem-resistant Klebsiella pneumoniae (CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R) K. pneumoniae, and susceptible K. pneumoniae isolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of the wzi and bla KPC genes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. The bla KPC-3 gene (30%) was restricted to ST258/wzi154, whereas bla KPC-2 (70%) was observed for several wzi allele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas the K. pneumoniae susceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and the wzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted. Infections due to carbapenem-resistant Enterobacteriaceae have emerged as an important public health problem over the past decade and are now considered an urgent antibiotic-resistant threat by the Centers for Disease Control and Prevention (CDC), the category of greatest concern (1). In the United States, carbapenem resistance among Enterobacteriaceae is primarily attributable to the production of the Klebsiella pneumoniae carbapenemase (KPC) (2, 3), which is plasmid mediated and most commonly encountered in K. pneumoniae in nosocomial settings (4, 5). Bloodstream infections (BSIs) caused by carbapenem-resistant K. pneumoniae (CRKP) are associated with particularly high mortality rates (6-8), with previous studies reporting hospital mortality rates of 40 to 70%, compared to rates of 20 to 30% among matched patients with bacteremia due to susceptible K. pneumoniae (4, 9).A single clone, multilocus sequence type 258 (ST258), has been found to account for the majority of CRKP infections in the United States and was identified among 70% of isolates s...

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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 79%

Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

et al. 2015

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“…pKpQIL-like plasmids from the New York and New Jersey isolates were associated mostly with bla KPC-2 and to a lesser extent with bla KPC-3 , whereas the pKpQIL plasmids from Israel were associated mainly with bla (194,195). This suggests that ST258 isolates with bla KPC-3 on pKpQIL plasmids were introduced into Israel from the United States during the mid-2000s (a founder effect), followed by clonal expansion in Israel.…”

Section: Plasmids Associated With K Pneumoniae St258mentioning

confidence: 83%

“…A retrospective plasmid analysis of K. pneumoniae strains with bla KPC from the New York and New Jersey areas isolated during the early 2000s showed that ST258 contained bla KPC-2 and bla KPC-3 on pKpQIL-like plasmids, which were nearly identical to the Israeli plasmid pKpQIL described in 2006 (194). pKpQIL-like plasmids from the New York and New Jersey isolates were associated mostly with bla KPC-2 and to a lesser extent with bla KPC-3 , whereas the pKpQIL plasmids from Israel were associated mainly with bla (194,195).…”

Section: Plasmids Associated With K Pneumoniae St258mentioning

confidence: 99%

The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae

2015

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SUMMARY Escherichia coli sequence type 131 (ST131) and Klebsiella pneumoniae ST258 emerged in the 2000s as important human pathogens, have spread extensively throughout the world, and are responsible for the rapid increase in antimicrobial resistance among E. coli and K. pneumoniae strains, respectively. E. coli ST131 causes extraintestinal infections and is often fluoroquinolone resistant and associated with extended-spectrum β-lactamase production, especially CTX-M-15. K. pneumoniae ST258 causes urinary and respiratory tract infections and is associated with carbapenemases, most often KPC-2 and KPC-3. The most prevalent lineage within ST131 is named fimH30 because it contains the H30 variant of the type 1 fimbrial adhesin gene, and recent molecular studies have demonstrated that this lineage emerged in the early 2000s and was then followed by the rapid expansion of its sublineages H30-R and H30-Rx. K. pneumoniae ST258 comprises 2 distinct lineages, namely clade I and clade II. Moreover, it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Epidemic plasmids with bla CTX-M and bla KPC belonging to incompatibility group F have contributed significantly to the success of these clones. E. coli ST131 and K. pneumoniae ST258 are the quintessential examples of international multidrug-resistant high-risk clones.

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“…Members of the pKpQIL plasmid family have been responsible globally for a number of CRE outbreaks (3,5,7,31,(33)(34)(35)(36). In pKpQIL and related plasmids, the bla KPC gene is located within a Tn4401 transposon sequence (4,37,38).…”

Section: Discussionmentioning

confidence: 99%

A Rapid Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Method for Single-Plasmid Tracking in an Outbreak of Carbapenem-Resistant Enterobacteriaceae

et al. 2014

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e Carbapenem-resistant Enterobacteriaceae (CRE) have spread globally and represent a serious and growing threat to public health. Rapid methods for tracking plasmids carrying carbapenemase genes could greatly benefit infection control efforts. Here, we demonstrate that real-time, direct tracking of a single plasmid in a bacterial strain responsible for an outbreak is possible using a commercial matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. In this case, we retrospectively tracked the bla KPC carbapenemase gene-bearing pKpQIL plasmid responsible for a CRE outbreak that occurred at the NIH Clinical Center in 2011. An ϳ11,109-Da MS peak corresponding to a gene product of the bla KPC pKpQIL plasmid was identified and characterized using a combination of proteomics and molecular techniques. This plasmid peak was present in spectra from retrospectively analyzed K. pneumoniae outbreak isolates, concordant with results from whole-genome sequencing, and absent from a diverse control set of bla KPC -negative clinical Enterobacteriaceae isolates. Notably, the gene characterized here is located adjacent to the bla KPC Tn4401 transposon on the pKpQIL plasmid. Sequence analysis demonstrates the presence of this gene in other bla KPC Tn4401-containing plasmids and suggests that this signature MS peak may be useful in tracking other plasmids conferring carbapenem resistance. Plasmid identification using this MALDI-TOF MS method was accomplished in as little as 10 min from isolated colonies and 30 min from positive (spiked) blood cultures, demonstrating the potential clinical utility for real-time plasmid tracking in an outbreak.

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Comparative Genomic Analysis of KPC-Encoding pKpQIL-Like Plasmids and Their Distribution in New Jersey and New York Hospitals

Cited by 96 publications

References 33 publications

Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates

The Role of Epidemic Resistance Plasmids and International High-Risk Clones in the Spread of Multidrug-Resistant Enterobacteriaceae

A Rapid Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Method for Single-Plasmid Tracking in an Outbreak of Carbapenem-Resistant Enterobacteriaceae

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