Summary Background Klebsiella pneumoniae is a leading public health threat due to its increasing prevalence of antibiotic resistance. Gastrointestinal carriage of K. pneumoniae is a risk factor for subsequent infections in hospitalised patients. We determined risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonising humans in a representative sample of a general population. Methods 2,975 individuals (54% women) ≥40y participating in the population-based Tromso Study 7 (2015-2016) were included. Faecal samples were screened for K. pneumoniae which were characterised using whole-genome sequencing. Risk factors for carriage were analysed using data from the Norwegian Prescription Database and questionnaires, using multivariable logistic regression. Findings Prevalence of K. pneumoniae gastrointestinal carriage was 16·3% (95% CI 15·0-17·7%) with no gender difference. Risk factors associated with carriage included age ≥60y, travel to Greece or Asia past 12 months (adjusted odds ratio 1·49, 95% CI 1·11-2·00), Crohn’s disease/ulcerative colitis (2·26, 1·20-4·27), use of protein pump inhibitors (1·62, 1·18-2·22) and non-steroidal anti-inflammatory drugs past six months (1·38, 1·04-1·84), and antibiotic use last month (1·73, 1·05-2·86). Prevalence was higher among those having used combinations of drug classes and decreased over time with respect to preceding antibiotic use. The K. pneumoniae population was diverse with 300 sequence types among 484 isolates distributed across four phylogroups. Among the isolates, 5·2% and 11·6% harboured acquired resistance and virulence factors, respectively. Interpretation Identification of risk factors for gastrointestinal carriage in a representative sample of a general population allows for identification of individuals that may have a higher risk of extraintestinal infection during hospitalisation. The diverse population structure of K. pneumoniae carriage isolates reflects the ecologically adaptive capacity of the bacterium, and the low antibacterial consumption probably contributes to the low prevalence of resistance in clinical isolates in Norway.

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