Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages

Aasmund Fostervold; Niclas Raffelsberger; Marit A K Hetland; Ragna Bakksjø; Eva Bernhoff; Ørjan Samuelsen; Arnfinn Sundsfjord; Jan E Afset; Christopher F Berntsen; Roar Bævre-Jensen; Marit H Ebbesen; Karianne W Gammelsrud; Anja D Guleng; Nina Handal; Aleksandra Jakovljev; Simreen K Johal; Åshild Marvik; Ane Natvik; Rolf-Arne Sandnes; Ståle Tofteland; Jørgen V Bjørnholt; Iren H Löhr; Assoc. on behalf of The Norwegian Study Group on Klebsiella pneumoniae

doi:10.1016/j.jinf.2024.106155

Risk of death in Klebsiella pneumoniae bloodstream infections is associated with specific phylogenetic lineages

J Infect. 2024 Apr 2;88(5):106155. doi: 10.1016/j.jinf.2024.106155. Online ahead of print.

Authors

Aasmund Fostervold¹, Niclas Raffelsberger², Marit A K Hetland³, Ragna Bakksjø⁴, Eva Bernhoff⁴, Ørjan Samuelsen⁵, Arnfinn Sundsfjord⁶, Jan E Afset⁷, Christopher F Berntsen⁸, Roar Bævre-Jensen⁹, Marit H Ebbesen¹⁰, Karianne W Gammelsrud¹¹, Anja D Guleng¹², Nina Handal¹³, Aleksandra Jakovljev⁷, Simreen K Johal¹⁴, Åshild Marvik¹⁵, Ane Natvik¹⁶, Rolf-Arne Sandnes¹⁷, Ståle Tofteland¹⁸, Jørgen V Bjørnholt¹¹, Iren H Löhr¹⁹; Assoc. on behalf of The Norwegian Study Group on Klebsiella pneumoniae

Affiliations

¹ Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway; Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway. Electronic address: aasmund.fostervold@sus.no.
² Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway; Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
³ Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway; Department of Biological Sciences, Faculty of Mathematics and Natural Sciences, University of Bergen, Bergen, Norway.
⁴ Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway.
⁵ Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway; Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
⁶ Department of Medical Biology, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway; Norwegian National Advisory Unit on Detection of Antimicrobial Resistance, Department of Microbiology and Infection Control, University Hospital of North Norway, Tromsø, Norway.
⁷ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medical Microbiology, St. Olav's Hospital, Trondheim University hospital, Trondheim, Norway.
⁸ Department of Internal Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.
⁹ Department of Medical Microbiology, Vestre Viken Hospital Trust, Drammen, Norway.
¹⁰ Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
¹¹ Department of Microbiology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
¹² Centre for Laboratory Medicine, Østfold Hospital Trust, Kalnes, Norway.
¹³ Department of Microbiology and Infection control, Akershus University Hospital, Lørenskog, Norway.
¹⁴ Department of Medical Microbiology, Nordland Hospital Trust, Bodø, Norway.
¹⁵ Department of Microbiology, Vestfold Hospital Trust, Tønsberg, Norway.
¹⁶ Department of Medical Microbiology, Vestre Viken Hospital Trust, Bærum, Norway.
¹⁷ Department of Medical Microbiology, Innlandet Hospital Trust, Lillehammer, Norway.
¹⁸ Department of Microbiology, Hospital of Southern Norway Trust, Kristiansand, Norway.
¹⁹ Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway; Department of Medical Microbiology, Stavanger University Hospital, Stavanger, Norway.

PMID: 38574775
DOI: 10.1016/j.jinf.2024.106155

Abstract

Background: Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear.

Methods: In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages.

Findings: We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10-3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98-2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46).

Conclusion: Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.

Keywords: Bloodstream infection; Cohort; ESBL; Klebsiella; MDR; Multi-centre; Outcome; Variicola; Whole-genome sequencing.