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

Author:

Roach David J123ORCID,Sridhar Sushmita13ORCID,Oliver Elizabeth3,Rao Sowmya R4,Slater Damien M3,Hwang Wontae3,Hutt Vater Kian3,Dinesh Anupama3,Qadri Firdausi5,Chisti Mohammod J5,Pierce Virginia M6,Turbett Sarah E37ORCID,Bhattacharyya Roby P13,Worby Colin J1ORCID,Earl Ashlee M1,LaRocque Regina C3ORCID,Harris Jason B38

Affiliation:

1. The Broad Institute of MIT and Harvard , Boston, Massachusetts , USA

2. Division of Infectious Diseases, Brigham and Women's Hospital , Boston, Massachusetts , USA

3. Division of Infectious Diseases, Massachusetts General Hospital , Boston, Massachusetts , USA

4. Department of Global Health, Boston University , Boston, Massachusetts , USA

5. Dhaka Hospital, International Centre for Diarrheal Disease Research , Bangladesh

6. Department of Pathology, University of Michigan Medical School , Ann Arbor, Michigan , USA

7. Department of Pathology, Massachusetts General Hospital , Boston, Massachusetts , USA

8. Department of Pediatrics, Harvard Medical School , Boston, Massachusetts , USA

Abstract

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.

Funder

National Institutes of Health

Center for Global Health Research Development Award

National Institute of Allergy and Infectious Diseases

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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