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.

FIG 1

Multilocus sequence type and wzi allele type diversity in susceptible, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R), and carbapenem-resistant K. pneumoniae (CRKP) isolates. (a) ST diversity among all isolates, with the number of isolates belonging to each ST being represented by a section of the pie graph. (b) ST variability according to susceptibility phenotype. Among the 194 susceptible isolates, 127 different STs were identified, compared to 20 different STs among 30 Ceph-R isolates and only 10 STs among 48 CRKP isolates. (c) Numbers of STs shared by the 3 resistance groups, which were limited. (d and e) wzi allele type variability among Ceph-R and CRKP (d) and ST258 (e) isolates, with the number of isolates belonging to each allele type being depicted by a section of the pie graph. There were 18 wzi allele types identified among 30 Ceph-R isolates and 12 wzi allele types seen among 47 CRKP isolates. The 32 ST258 isolates were subdivided into six wzi allele types. Among Ceph-R and CRKP isolates, there were 4 shared wzi allele types.

FIG 2

Clonal diversity of serial K. pneumoniae bloodstream infections in select patients. There were 9 patients with multiple positive blood cultures for whom collected isolates were of more than one sequence type (ST). Each bloodstream isolate is depicted by a rectangle. Susceptibility phenotypes are differentiated by color; gray bars, susceptible isolates; pink bars, Ceph-R isolates; green bars, CRKP isolates. Isolates of different STs that have the same susceptibility phenotype are differentiated by pattern but share the same color background. Thus, only patients 1, 2, and 9 have isolates of different susceptibility phenotypes and STs; all others have multiple isolates with the same resistance pattern but differing STs.