Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection

Abstract

Background: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI.

Methods: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022.

Results: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found.

Conclusions: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.

Keywords: Klebsiella pneumoniae; bacteremia; mortality modeling; virulence factors; whole-genome sequencing.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/clinical-and-genomic-characterization-of-a-large-cohort-of-patients-with-klebsiella-pneumoniae-bloodstream-infection/update

Figure 1.

Outcome stratified by infection sources and distribution of cancer class. A, Number of each primary infection source resulting in bacteremia in the population, delineated by outcome (discharge vs in-hospital death). B, Primary infection sources in patients with cancer according to cancer type; “hematologic other” indicates hematologic cancer other than leukemia. Abbreviations: GI, gastrointestinal; HEENT, head, ears, eyes, nose, and throat; SSTI, skin and soft-tissue infection.

Figure 2.

Phylogenetic tree of the 94 Klebsiella pneumoniae bloodstream infection isolates, a midpoint-rooted tree based on core single-nucleotide polymorphism aligned to reference strain NTUH-K2044. Column 1 shows the sequence types (STs) with ≥3 isolates represented; column 2, ceftriaxone resistance pattern; and column 3, the infection source. Branches are colored black or red for community-acquired or hospital-acquired infections, respectively. Abbreviations: AST, antimicrobial susceptibility testing; SSTI, skin and soft-tissue infection.

Figure 3.

Acquired determinants of antimicrobial resistance (AMR) and virulence factors within the prospective cohort. A, Histogram of the number of AMR genes present across isolates, which demonstrates that most isolates lacked resistance genes. B, Histogram of the number of antibiotic classes present across isolates. C, Histogram of the individual virulence factors across the population, which shows low prevalence of all factors other than yersiniabactin. D, Histogram of virulence scores across the population.