Community carriage of ESBL-producingEscherichia coliandKlebsiella pneumoniae: A cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates

Abstract

AbstractThe global prevalence of infections caused by ESBL-producing Enterobacterales (ESBL-E) is increasing and forEscherichia coliobservations 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-producingE. coliandKlebsiella pneumoniae(ESBL-Ec/Kp) in a general adult population, examine risk factors, and compare carriage isolates with contemporary clinical isolates.Fecal samples obtained from 4999 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% 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 (AOR 3.47, 95% CI 2.18-5.51).E. coliST131 was most prevalent in both collections. However, the ST131 proportion was significantly lower in carriage (24%) vs. clinical isolates (58%, p<0.001). Carriage isolates were genetically more diverse with a higher proportion of phylogroup A (26% vs. 5%, p<0.001), indicating that ESBL gene acquisition occurs in a variety ofE. colilineages colonizing the gut. STs commonly related to extra-intestinal infections were more frequent in clinical isolates also carrying a higher prevalence of antimicrobial resistance, which could indicate clone associated pathogenicity.ImportanceESBL-producingE. coli(ESBL-Ec) andK. pneumoniae(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.