Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug 24;8(4):e0002523.
doi: 10.1128/msphere.00025-23. Epub 2023 Jun 12.

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

Niclas Raffelsberger  1   2 , Dorota Julia Buczek  2 , Kristian Svendsen  3 , Lars Småbrekke  3 , Anna Kaarina Pöntinen  4   5 , Iren H Löhr  6 , Lotte Leonore Eivindsdatter Andreassen  1 , Gunnar Skov Simonsen  1   2 ; Norwegian E. coli ESBL Study Group; Arnfinn Sundsfjord  2   4 , Kirsten Gravningen #  1   7   8 , Ørjan Samuelsen #  3   4
Collaborators, Affiliations

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

Niclas Raffelsberger et al. mSphere. .

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.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.

Keywords: Escherichia coli; Klebsiella pneumoniae; antimicrobial resistance; bacterial genomics; carriage; extended-spectrum β-lactamase; general population; risk factors.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig 1
Fig 1
Flow diagram of the study population, Tromsø7, 2015–2016. *Subgroup of the study population screened for K. pneumoniae carriage as previously described (25).
Fig 2
Fig 2
Flowchart and results of fecal sample screening for gastrointestinal carriage of ESBL-producing E. coli and K. pneumoniae in 4,999 participants in Tromsø7, 2015–2016.
Fig 3
Fig 3
Maximum-likelihood phylogenetic tree based on core genome alignment of the genomes of ESBL-E. coli carriage isolates from Tromsø7 (labeled gray, n = 166) and clinical isolates from NORM 2014 (blood isolates labeled with red and urine isolates with yellow, n = 118). The innermost ring illustrates phylogroups, followed by a ring with sequence types (STs), a ring with ST131 subclades, and a ring with fimH types (ND, not detected). The heatmap shows the presence (blue color) or absence (white) of ESBL gene variants and other relevant β-lactamases.
Fig 4
Fig 4
Phylogroup (labeled on the top) and sequence type (ST) distribution of ESBL-E. coli carriage isolates from Tromsø7 (n = 166) and clinical isolates from NORM 2014 (n = 118).
Fig 5
Fig 5
ESBL gene prevalence in ESBL-E. coli carriage isolates from the Tromsø7 study (n = 166) and clinical isolates from NORM 2014 (n = 118).
See this image and copyright information in PMC

References

    1. Antimicrobial Resistance C. 2022. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399:629–655. doi:10.1016/S0140-6736(21)02724-0 - DOI - PMC - PubMed
    1. NORM/NORM-VET 2021 . 2022. Usage of antimicrobial agents and occurrence of antimicrobial resistance in Norway. Tromsø/Oslo/Ås; ISSN: 1502-2307 (print)/1890- 9965 (electronic).
    1. Schwaber MJ, Carmeli Y. 2007. Mortality and delay in effective therapy associated with extended-spectrum beta-lactamase production in enterobacteriaceae bacteraemia: a systematic review and meta-analysis. J Antimicrob Chemother 60:913–920. doi:10.1093/jac/dkm318 - DOI - PubMed
    1. Scheuerman O, Schechner V, Carmeli Y, Gutiérrez-Gutiérrez B, Calbo E, Almirante B, Viale P-L, Oliver A, Ruiz-Garbajosa P, Gasch O, Gozalo M, Pitout J, Akova M, Peña C, Molina J, Hernández-Torres A, Venditti M, Prim N, Origüen J, Bou G, Tacconelli E, Tumbarello M, Hamprecht A, Karaiskos I, de la Calle C, Pérez F, Schwaber MJ, Bermejo J, Lowman W, Hsueh P-R, Navarro-San Francisco C, Bonomo RA, Paterson DL, Pascual A, Rodríguez-Baño J, REIPI/ESGBIS/INCREMENT investigators . 2018. Comparison of predictors and mortality between bloodstream infections caused by ESBL-producing Escherichia coli and ESBL-producing Klebsiella pneumoniae. Infect Control Hosp Epidemiol 39:660–667. doi:10.1017/ice.2018.63 - DOI - PubMed
    1. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N, Aboderin AO, Al-Abri SS, Awang Jalil N, Benzonana N, Bhattacharya S, Brink AJ, Burkert FR, Cars O, Cornaglia G, Dyar OJ, Friedrich AW, Gales AC, Gandra S, Giske CG, Goff DA, Goossens H, Gottlieb T, Guzman Blanco M, Hryniewicz W, Kattula D, Jinks T, Kanj SS, Kerr L, Kieny M-P, Kim YS, Kozlov RS, Labarca J, Laxminarayan R, Leder K, Leibovici L, Levy-Hara G, Littman J, Malhotra-Kumar S, Manchanda V, Moja L, Ndoye B, Pan A, Paterson DL, Paul M, Qiu H, Ramon-Pardo P, Rodríguez-Baño J, Sanguinetti M, Sengupta S, Sharland M, Si-Mehand M, Silver LL, Song W, Steinbakk M, Thomsen J, Thwaites GE, van der Meer JW, Van Kinh N, Vega S, Villegas MV, Wechsler-Fördös A, Wertheim HFL, Wesangula E, Woodford N, Yilmaz FO, Zorzet A. 2018. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318–327. doi:10.1016/S1473-3099(17)30753-3 - DOI - PubMed

Publication types

LinkOut - more resources