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
Authors: Raffelsberger Niclas , Buczek Dorota Julia , Svendsen Kristian , Småbrekke Lars , Pöntinen Anna Kaarina , Löhr Iren H. , Andreassen Lotte Leonore Eivindsdatter , Simonsen Gunnar Skov ,   Norwegian E. coli ESBL Study Group, Sundsfjord Arnfinn , Gravningen Kirsten , Samuelsen Ørjan , Handal Nina , Hafne Liv Jorunn , Lindemann Paul Christoffer , Norgaard Lovise Marie , Zaragkoulias Kyriakos , Nilsen Einar , Larsen Hege Elisabeth , Pino Marcela , Hermansen Nils Olav , Löhr Iren H. , Jakovljev Aleksandra , Tofteland Ståle , Papp Kristina , Simonsen Gunnar Skov , Marvik Åshild , Pullar Nadine Durema , Bævre-Jensen Roar Magne , Kanestrøm Anita 
Published: June 2023

ABSTRACT

The global prevalence of infections caused by extended-spectrum β-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.

IMPORTANCE
ESBL-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.