Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: a prospective study using whole-genome sequencing Julien Coussement 1,2 , Maria Angeles Argudı ´n 1 , Ame ´lie Heinrichs 1 , Judith Racape ´ 3,4 , Ricardo de Mendonc ¸a 1 , Louise Nienhaus 1 , Alain Le Moine 4 , Sandrine Roisin 1 , Magali Dode ´mont 1 , Fre ´de ´rique Jacobs 2 , Daniel Abramowicz 5 , Brian D. Johnston 6 , James R. Johnson 6, * and Olivier Denis 1,7, * 1 Department of Microbiology, CUB-Ho ˆpital Erasme, Universite ´ Libre de Bruxelles, Brussels, Belgium, 2 Division of Infectious Diseases, CUB- Ho ˆpital Erasme, Universite ´ Libre de Bruxelles, Brussels, Belgium, 3 Research Center “Biostatistiques, Epide ´miologie et Recherche Clinique”, E ´ cole de Sante ´ Publique, Universite ´ Libre de Bruxelles, Brussels, Belgium, 4 Department of Nephrology, CUB-Ho ˆpital Erasme, Universite ´ Libre de Bruxelles, Brussels, Belgium, 5 Department of Nephrology-Hypertension, Universitair Ziekenhuis Antwerpen, Antwerp University, Antwerpen, Belgium, 6 Minneapolis Veterans Health Care System, Minneapolis, MN, USA and 7 E ´ cole de Sante ´ Publique, Universite ´ Libre de Bruxelles, Brussels, Belgium Correspondence and offprint requests to: Julien Coussement; E-mail: jcoussem@ulb.ac.be *These authors contributed equally to this work. ABSTRACT Background. Urinary tract infection is the most common infection among kidney transplant recipients (KTRs). Many transplant physicians fear that host compromise will allow low- virulence strains to cause pyelonephritis in KTRs, so they often treat asymptomatic bacteriuria with antibiotics. Identification of the host/microbe factors that determine the clinical presenta- tion (i.e. pyelonephritis versus asymptomatic bacteriuria) once an Escherichia coli strain enters a KTRs bladder could inform management decisions. Methods. We prospectively collected all E. coli isolates causing either pyelonephritis or asymptomatic bacteriuria in KTRs at our institution (December 2012–June 2015). Whole-genome se- quencing was used to assess bacterial characteristics (carriage of 48 virulence genes and phylogenetic and clonal background). Host parameters were also collected. Results. We analysed 72 bacteriuria episodes in 54 KTRs (53 pyelonephritis, 19 asymptomatic bacteriuria). The pyelonephri- tis and asymptomatic bacteriuria isolates exhibited a similar to- tal virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P ¼ 0.57] and for individual viru- lence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteri- uria 0%; P ¼ 0.002). No other significant between-group differ- ences were apparent for 86 other bacterial and host variables. Conclusions. Our findings suggest that bacterial adherence plays a role in the pathogenesis of pyelonephritis in KTRs despite significantly altered host urinary tract anatomy and weakened immunity. Whether KTRs might benefit from tar- geted therapies (e.g. vaccination or inhibitors of fimbrial adhe- sion) has yet to be studied. Keywords: ExPEC, NGS, UPEC, urinary tract infections, virulome INTRODUCTION Urinary tract infection (UTI) is the most common infection among kidney transplant recipients (KTRs) [1]. Graft pyelone- phritis (i.e. infection of the transplanted kidney) may decrease kidney function, be associated with graft rejection and reduce quality of life [2–4]. Accordingly, most transplant physicians screen for and treat asymptomatic bacteriuria among KTRs with the hope of reducing the incidence of subsequent UTI, in- cluding pyelonephritis [5]. However, this common practice is not supported by a recent systematic review [6]. Importantly, antibiotic use is a major driver for antimicrobial resistance and promotes Clostridium difficile infection. Several elements may explain why antibiotic therapy for asymptomatic bacteriuria is common after kidney transplanta- tion [7]. Specifically, KTRs have altered host defenses due to both immune deficiency (from anti-rejection drugs) and uri- nary tract abnormalities (from the heterotopic transplant itself and possible complications thereof, including vesicoureteral re- flux) [8]. Therefore many transplant physicians fear that low-- virulence bacteria may cause pyelonephritis and thus treat asymptomatic bacteriuria preemptively [9, 10]. V C The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. 1 ORIGINAL ARTICLE Nephrol Dial Transplant (2018) 1–8 doi: 10.1093/ndt/gfy292 Downloaded from https://academic.oup.com/ndt/advance-article-abstract/doi/10.1093/ndt/gfy292/5124339 by Kaohsiung Medical University Library user on 19 October 2018