Community carriage of ESBL-producing Escherichia coli and Klebsiella pneumoniae: a cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates.

The global prevalence of infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) is increasing, and for Escherichia coli, observations indicate that this is partly driven by community-onset cases. The ESBL-E population structure in the community is scarcely described, and data on risk factors for carriage are conflicting. Here, we report the prevalence and population structure of fecal ESBL-producing E. coli and Klebsiella pneumoniae (ESBL-Ec/Kp) in a general adult population, examine risk factors, and compare carriage isolates with contemporary clinical isolates. Fecal samples obtained from 4,999 participants (54% women) ≥40 years in the seventh survey of the population-based Tromsø Study, Norway (2015, 2016), were screened for ESBL-Ec/Kp. In addition, we included 118 ESBL-Ec clinical isolates from the Norwegian surveillance program in 2014. All isolates were whole-genome sequenced. Risk factors associated with carriage were analyzed using multivariable logistic regression. ESBL-Ec gastrointestinal carriage prevalence was 3.3% [95% confidence interval (CI) 2.8%-3.9%, no sex difference] and 0.08% (0.02%-0.20%) for ESBL-Kp. For ESBL-Ec, travel to Asia was the only independent risk factor (adjusted odds ratio 3.46, 95% CI 2.18-5.49). E. coli ST131 was most prevalent in both collections. However, the ST131 proportion was significantly lower in carriage (24%) versus clinical isolates (58%, P < 0.001). Carriage isolates were genetically more diverse with a higher proportion of phylogroup A (26%) than clinical isolates (5%, P < 0.001), indicating that ESBL gene acquisition occurs in a variety of E. coli lineages colonizing the gut. STs commonly related to extraintestinal infections were more frequent in clinical isolates also carrying a higher prevalence of antimicrobial resistance, which could indicate clone-associated pathogenicity.IMPORTANCEESBL-Ec and ESBL-Kp are major pathogens in the global burden of antimicrobial resistance. However, there is a gap in knowledge concerning the bacterial population structure of human ESBL-Ec/Kp carriage isolates in the community. We have examined ESBL-Ec/Kp isolates from a population-based study and compared these to contemporary clinical isolates. The large genetic diversity of carriage isolates indicates frequent ESBL gene acquisition, while those causing invasive infections are more clone dependent and associated with a higher prevalence of antibiotic resistance. The knowledge of factors associated with ESBL carriage helps to identify patients at risk to combat the spread of resistant bacteria within the healthcare system. Particularly, previous travel to Asia stands out as a major risk factor for carriage and should be considered in selecting empirical antibiotic treatment in critically ill patients.

Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population: a cross-sectional study of risk factors and bacterial genomic diversity.

Antibiotic resistant Klebsiella pneumoniae is a leading public health threat and gastrointestinal carriage is an established risk factor for subsequent infections during hospitalization. Our study contributes new knowledge of risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonizing humans in a representative sample of a general population in a community setting. Altogether, 2,975 participants (54% women) >40 y in the population-based Tromsø Study: Tromsø7, Norway (2015-2016) were included. Fecal samples were screened for K. pneumoniae, which were characterized using whole-genome sequencing. Risk factors for carriage were analyzed using multivariable logistic regression on data from questionnaires and the Norwegian Prescription Database. Prevalence of K. pneumoniae gastrointestinal carriage was 16.3% (95% CI 15.0-17.7, no gender difference). Risk factors associated with carriage included age ≥60 y, 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 proton pump inhibitors (1.62, 1.18-2.22) and non-steroidal anti-inflammatory drugs past 6 months (1.38, 1.04-1.84), and antibiotic use the 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. Only 5.2% of isolates harbored acquired resistance and 11.6% had virulence factors. Identification of risk factors for gastrointestinal carriage allows for identification of individuals that may have higher risk of extraintestinal infection during hospitalization. The findings that specific diseases and drugs used were associated with carriage show an impact of these possibly through modulating the human gut microbiota promoting colonization. The diverse population structure of carriage isolates reflects the ecologically adaptive capacity of the bacterium and challenges for vaccine prospects and the identification of reservoirs as a potential source for human colonization.