A Cross-Sectional Cohort Study of Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Patients with Traveler's Diarrhea

Oskar Ljungquist, Angela Camporeale, Shoeib Nematzadeh, Christian G Giske, Fredrik Resman, Kristian Riesbeck, Johan Tham, Oskar Ljungquist, Angela Camporeale, Shoeib Nematzadeh, Christian G Giske, Fredrik Resman, Kristian Riesbeck, Johan Tham

Abstract

Patients with traveler's diarrhea (TD) can acquire extended-spectrum-beta-lactamase (ESBL)-producing members of the Enterobacterales (EPE) during travel to areas of endemicity. The aim of the present study was to investigate the prevalence and characteristics of EPE carriage in travelers from southern Sweden who were sampled for bacterial diagnostics of TD compared to those of EPE carriage 10 years ago. Clinical samples sent for culture of common causes of bacterial enterocolitis, if the referral stated foreign travel, were included in the study. Antimicrobial susceptibility testing was done according to the EUCAST disk diffusion test method. EPE strains were subjected to whole-genome sequencing (WGS). Eighty-four of 303 patients carried a total of 92 ESBL-producing members of the Enterobacterales The overall prevalence of EPE in tested samples was thus 28%, compared to 24% 10 years earlier (P = 0.33). Among 86 strains available for WGS, 47 different sequence types (STs) were identified, and there were only 5 ST131 strains. Of the 79 Escherichia coli isolates, 76% carried at least one fim (type 1 fimbria) gene, 29% carried at least one pap (p-fimbriae) gene, and 43% were extraintestinal pathogenic E. coli (ExPEC) or uropathogenic E. coli (UPEC). Over half of the E. coli strains (57%) were intestinal pathogenic E. coli, most commonly enteroaggregative E. coli (EAEC) (33%), and enteroinvasive E. coli EIEC (22%). A relatively high proportion of patients with traveler's diarrhea carry EPE, but there was no significant increase compared to 10 years ago. Most E. coli strains were intestinal pathogenic strains. A comparatively high proportion of the strains were ExPEC/UPEC, many expressing the virulence genes pap and/or fim (This project was assigned ClinicalTrials.gov number NCT03866291.).

Keywords: E. coli; ESBL; beta-lactamases; pAmpC.

Copyright © 2020 Ljungquist et al.

Figures

FIG 1
FIG 1
Susceptibility testing of EPE strains (n = 92). The percentages of strains classified as susceptible; susceptible, increased exposure; and resistant are shown. Abbreviations: pip-taz, piperacillin-tazobactam; cefta-avi, ceftazidime-avibactam; cefta, ceftazidime; cefto-taz, ceftolozane tazobactam; imi, imipenem; mero, meropenem; genta, gentamicin; tobm, tobramycin; amika, amikacin; tmx, trimethoprim-sulfamethoxazole; cipro, ciprofloxacin; temo, temocillin. All percentages were rounded off to the nearest integer.

References

    1. Tham J, Odenholt I, Walder M, Brolund A, Ahl J, Melander E. 2010. Extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers' diarrhoea. Scand J Infect Dis 42:275–280. doi:10.3109/00365540903493715.
    1. Peirano G, Laupland KB, Gregson DB, Pitout JD. 2011. Colonization of returning travelers with CTX-M-producing Escherichia coli. J Travel Med 18:299–303. doi:10.1111/j.1708-8305.2011.00548.x.
    1. Tangden T, Cars O, Melhus A, Lowdin E. 2010. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers. Antimicrob Agents Chemother 54:3564–3568. doi:10.1128/AAC.00220-10.
    1. Barreto Miranda I, Ignatius R, Pfuller R, Friedrich-Janicke B, Steiner F, Paland M, Dieckmann S, Schaufler K, Wieler LH, Guenther S, Mockenhaupt FP. 2016. High carriage rate of ESBL-producing Enterobacteriaceae at presentation and follow-up among travellers with gastrointestinal complaints returning from India and Southeast Asia. J Travel Med 23:tav024. doi:10.1093/jtm/tav024.
    1. Lubbert C, Straube L, Stein C, Makarewicz O, Schubert S, Mossner J, Pletz MW, Rodloff AC. 2015. Colonization with extended-spectrum beta-lactamase-producing and carbapenemase-producing Enterobacteriaceae in international travelers returning to Germany. Int J Med Microbiol 305:148–156. doi:10.1016/j.ijmm.2014.12.001.
    1. Ostholm-Balkhed A, Tarnberg M, Nilsson M, Nilsson LE, Hanberger H, Hallgren A, Travel Study Group of Southeast Sweden. 2013. Travel-associated faecal colonization with ESBL-producing Enterobacteriaceae: incidence and risk factors. J Antimicrob Chemother 68:2144–2153. doi:10.1093/jac/dkt167.
    1. Kuenzli E, Jaeger VK, Frei R, Neumayr A, DeCrom S, Haller S, Blum J, Widmer AF, Furrer H, Battegay M, Endimiani A, Hatz C. 2014. High colonization rates of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in Swiss travellers to South Asia—a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors. BMC Infect Dis 14:528. doi:10.1186/1471-2334-14-528.
    1. Ruppe E, Armand-Lefevre L, Estellat C, Consigny PH, El Mniai A, Boussadia Y, Goujon C, Ralaimazava P, Campa P, Girard PM, Wyplosz B, Vittecoq D, Bouchaud O, Le Loup G, Pialoux G, Perrier M, Wieder I, Moussa N, Esposito-Farese M, Hoffmann I, Coignard B, Lucet JC, Andremont A, Matheron S. 2015. High rate of acquisition but short duration of carriage of multidrug-resistant Enterobacteriaceae after travel to the tropics. Clin Infect Dis 61:593–600. doi:10.1093/cid/civ333.
    1. Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A, Grobusch MP, Lashof AMO, Molhoek N, Schultsz C, Stobberingh EE, Verbrugh HA, de Jong MD, Melles DC, Penders J. 2017. Import and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis 17:78–85. doi:10.1016/S1473-3099(16)30319-X.
    1. Vading M, Kabir MH, Kalin M, Iversen A, Wiklund S, Naucler P, Giske CG. 2016. Frequent acquisition of low-virulence strains of ESBL-producing Escherichia coli in travellers. J Antimicrob Chemother 71:3548–3555. doi:10.1093/jac/dkw335.
    1. European Antimicrobial Resistance Surveillance Network. 2018. Surveillance of antimicrobial resistance in Europe 2018. .
    1. Sweden Public Health Agency. 2020. Extended Spectrum Betalactamase (ESBL)-producerande Enterobacteriaceae 2020. .
    1. Woerther PL, Andremont A, Kantele A. 2017. Travel-acquired ESBL-producing Enterobacteriaceae: impact of colonization at individual and community level. J Travel Med 24:S29–S34. doi:10.1093/jtm/taw101.
    1. Woerther PL, Burdet C, Chachaty E, Andremont A. 2013. Trends in human fecal carriage of extended-spectrum beta-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 26:744–758. doi:10.1128/CMR.00023-13.
    1. Frost I, Van Boeckel TP, Pires J, Craig J, Laxminarayan R. 2019. Global geographic trends in antimicrobial resistance: the role of international travel. J Travel Med 26:taz036. doi:10.1093/jtm/taz036.
    1. Van Aken S, Lund N, Ahl J, Odenholt I, Tham J. 2014. Risk factors, outcome and impact of empirical antimicrobial treatment in extended-spectrum beta-lactamase-producing Escherichia coli bacteraemia. Scand J Infect Dis 46:753–762. doi:10.3109/00365548.2014.937454.
    1. Laaveri T, Vilkman K, Pakkanen SH, Kirveskari J, Kantele A. 2018. A prospective study of travellers' diarrhoea: analysis of pathogen findings by destination in various (sub)tropical regions. Clin Microbiol Infect 24:908.E9–908.E16. doi:10.1016/j.cmi.2017.10.034.
    1. Zboromyrska Y, Hurtado JC, Salvador P, Alvarez-Martinez MJ, Valls ME, Mas J, Marcos MA, Gascon J, Vila J. 2014. Aetiology of traveller's diarrhoea: evaluation of a multiplex PCR tool to detect different enteropathogens. Clin Microbiol Infect 20:O753–O759. doi:10.1111/1469-0691.12621.
    1. Max Roser. 2017. Tourism. Our World in Data. .
    1. Angelin M, Forsell J, Granlund M, Evengard B, Palmgren H, Johansson A. 2015. Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad: a prospective study. Travel Med Infect Dis 13:223–229. doi:10.1016/j.tmaid.2015.04.007.
    1. Lausch KR, Fuursted K, Larsen CS, Storgaard M. 2013. Colonisation with multi-resistant Enterobacteriaceae in hospitalised Danish patients with a history of recent travel: a cross-sectional study. Travel Med Infect Dis 11:320–323. doi:10.1016/j.tmaid.2013.06.004.
    1. Kantele A, Laaveri T, Mero S, Vilkman K, Pakkanen SH, Ollgren J, Antikainen J, Kirveskari J. 2015. Antimicrobials increase travelers' risk of colonization by extended-spectrum betalactamase-producing Enterobacteriaceae. Clin Infect Dis 60:837–846. doi:10.1093/cid/ciu957.
    1. Ny S, Lofmark S, Borjesson S, Englund S, Ringman M, Bergstrom J, Naucler P, Giske CG, Byfors S. 2017. Community carriage of ESBL-producing Escherichia coli is associated with strains of low pathogenicity: a Swedish nationwide study. J Antimicrob Chemother 72:582–588. doi:10.1093/jac/dkw419.
    1. Dhanji H, Patel R, Wall R, Doumith M, Patel B, Hope R, Livermore DM, Woodford N. 2011. Variation in the genetic environments of bla(CTX-M-15) in Escherichia coli from the faeces of travellers returning to the United Kingdom. J Antimicrob Chemother 66:1005–1012. doi:10.1093/jac/dkr041.
    1. Kantele A, Laaveri T, Mero S, Hakkinen IMK, Kirveskari J, Johnston BD, Johnson JR. 2020. Despite predominance of uropathogenic/extraintestinal pathotypes among travel-acquired extended-spectrum beta-lactamase-producing Escherichia coli, the most commonly associated clinical manifestation is travelers' diarrhea. Clin Infect Dis 70:210–218. doi:10.1093/cid/ciz182.
    1. Statistics Sweden Population and Economic Welfare Statistics Unit. 2019. Population in the country, counties and municipalities on 31 December 2017 and population change in 2017 Stockholm. SCB, Stockholm, Sweden: . Accessed 11 January 2020.
    1. Wick RR, Judd LM, Gorrie CL, Holt KE. 2017. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 13:e1005595. doi:10.1371/journal.pcbi.1005595.
    1. Joensen KG, Scheutz F, Lund O, Hasman H, Kaas RS, Nielsen EM, Aarestrup FM. 2014. Real-time whole-genome sequencing for routine typing, surveillance, and outbreak detection of verotoxigenic Escherichia coli. J Clin Microbiol 52:1501–1510. doi:10.1128/JCM.03617-13.
    1. Liu B, Zheng D, Jin Q, Chen L, Yang J. 2019. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res 47:D687–D692. doi:10.1093/nar/gky1080.
    1. Johnson JR, Murray AC, Gajewski A, Sullivan M, Snippes P, Kuskowski MA, Smith KE. 2003. Isolation and molecular characterization of nalidixic acid-resistant extraintestinal pathogenic Escherichia coli from retail chicken products. Antimicrob Agents Chemother 47:2161–2168. doi:10.1128/AAC.47.7.2161-2168.2003.
    1. Spurbeck RR, Dinh PC Jr, Walk ST, Stapleton AE, Hooton TM, Nolan LK, Kim KS, Johnson JR, Mobley HL. 2012. Escherichia coli isolates that carry vat, fyuA, chuA, and yfcV efficiently colonize the urinary tract. Infect Immun 80:4115–4122. doi:10.1128/IAI.00752-12.
    1. Beghain J, Bridier-Nahmias A, Le Nagard H, Denamur E, Clermont O. 2018. ClermonTyping: an easy-to-use and accurate in silico method for Escherichia genus strain phylotyping. Microb Genom 4:e000192. doi:10.1099/mgen.0.000192.

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