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

Abstract

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...

Combination Regimens for Treatment of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

“…Exclusion of these patients may also account for the paradoxically lower mortality rates seen in immunosuppressed patients. Although we did not perform molecular testing on all isolates to identify carbapenem resistance mechanisms, two recent studies of CRKP BSI in New York City, both of which included the centers in this study, reported that 94% and 100% of CRKP isolates were KPC producers (29,30). Our molecular testing of a limited number of isolates in this study confirmed these findings.…”

Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection

“…This is illustrated by the phenotypically heterogeneous K. pneumoniae strains that were isolated repeatedly from the airway and blood over a 3-month period of a nonneutropenic mechanically ventilated patient ( Figure 1A). We used a murine model of pulmonary infection to characterize the innate immune response to ST258 isolate 35 (KP35), a CRKP isolate representative of many strains recovered from our hospital, expressing the most common cps (capsular protein) and wzi (cps component) genotypes (1). Following intranasal delivery of a high inoculum (10 8 CFU) to WT C57BL/6J mice, greater than 10 4 CFU/ml were isolated from the lungs and airways, accompanied by high-grade bacteremia and weight loss over the 96-hour course of infection ( Figure 1, B and C).…”

“…We selected the representative clinical isolate KP35 from a patient with bacteremia for comprehensive study (1). It was chosen because it is a common isolate recovered in our institution and it expresses the most common cps and wzi genotypes.…”

Klebsiella pneumoniae: Going on the Offense with a Strong Defense

“…K antigens have been traditionally assigned by using serological methods (201). Recently, however, K-antigen typing is often performed by sequencing of the wzi locus (206)(207)(208)(209)(210). This locus is present in all capsular types of K. pneumoniae, and different wzi locus sequences are strongly associated with specific K antigens.…”