title: Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates.
abstract: Despite 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 blaKPC 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 blaKPC-3 gene (30%) was restricted to ST258/wzi154, whereas blaKPC-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.
authors: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
authors: Angela
authors: A
authors: Gomez-Simmonds
authors: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
authors: Michelle
authors: M
authors: Greenman
authors: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
authors: Sean B
authors: SB
authors: Sullivan
authors: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
authors: Joshua P
authors: JP
authors: Tanner
authors: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
authors: Madeleine G
authors: MG
authors: Sowash
authors: Department of Pathology and Cell Biology, Clinical Microbiology Laboratory, Columbia University Medical Center, New York, New York, USA.
authors: Susan
authors: S
authors: Whittier
authors: Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA au2110@cumc.columbia.edu.
authors: Anne-Catrin
authors: AC
authors: Uhlemann
mesh_terms: D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D005798:Genes, Bacterial; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D009519:New York City / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D018805:Sepsis / Q000453:epidemiology / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D062606:Tertiary Care Centers