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, Maria Angeles Argudín, Amélie Heinrichs, Judith Racapé, Ricardo de Mendonça, Louise Nienhaus, Alain Le Moine, Sandrine Roisin, Magali Dodémont, Frédérique Jacobs, Daniel Abramowicz, Brian D Johnston, James R Johnson, Olivier Denis

Research output: Contribution to journalArticle

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 presentation (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 sequencing 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 pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences 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 targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.

Original languageEnglish (US)
Pages (from-to)878-885
Number of pages8
JournalNephrology Dialysis Transplantation
Volume34
Issue number5
DOIs
StatePublished - Jan 1 2019

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Bacteriuria
Pyelonephritis
Genome
Prospective Studies
Escherichia coli
Kidney
Virulence
Genes
Operon
Transplant Recipients
Urinary Tract
Urinary Tract Infections
Fear
Immunity
Anatomy
Vaccination
Urinary Bladder
Anti-Bacterial Agents
Physicians
Transplants

Keywords

  • ExPEC
  • NGS
  • UPEC
  • Urinary tract infections
  • Virulome

Cite this

Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria : A prospective study using whole-genome sequencing. / Coussement, Julien; Argudín, Maria Angeles; Heinrichs, Amélie; Racapé, Judith; de Mendonça, Ricardo; Nienhaus, Louise; Le Moine, Alain; Roisin, Sandrine; Dodémont, Magali; Jacobs, Frédérique; Abramowicz, Daniel; Johnston, Brian D; Johnson, James R; Denis, Olivier.

In: Nephrology Dialysis Transplantation, Vol. 34, No. 5, 01.01.2019, p. 878-885.

Research output: Contribution to journalArticle

Coussement, J, Argudín, MA, Heinrichs, A, Racapé, J, de Mendonça, R, Nienhaus, L, Le Moine, A, Roisin, S, Dodémont, M, Jacobs, F, Abramowicz, D, Johnston, BD, Johnson, JR & Denis, O 2019, 'Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: A prospective study using whole-genome sequencing', Nephrology Dialysis Transplantation, vol. 34, no. 5, pp. 878-885. https://doi.org/10.1093/ndt/gfy292
Coussement, Julien ; Argudín, Maria Angeles ; Heinrichs, Amélie ; Racapé, Judith ; de Mendonça, Ricardo ; Nienhaus, Louise ; Le Moine, Alain ; Roisin, Sandrine ; Dodémont, Magali ; Jacobs, Frédérique ; Abramowicz, Daniel ; Johnston, Brian D ; Johnson, James R ; Denis, Olivier. / Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria : A prospective study using whole-genome sequencing. In: Nephrology Dialysis Transplantation. 2019 ; Vol. 34, No. 5. pp. 878-885.
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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 presentation (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 sequencing 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 pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39{\%},versus asymptomatic bacteriuria 0{\%}; P = 0.002). No other significant between-group differences 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 targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.",
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T1 - Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria

T2 - A prospective study using whole-genome sequencing

AU - Coussement, Julien

AU - Argudín, Maria Angeles

AU - Heinrichs, Amélie

AU - Racapé, Judith

AU - de Mendonça, Ricardo

AU - Nienhaus, Louise

AU - Le Moine, Alain

AU - Roisin, Sandrine

AU - Dodémont, Magali

AU - Jacobs, Frédérique

AU - Abramowicz, Daniel

AU - Johnston, Brian D

AU - Johnson, James R

AU - Denis, Olivier

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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 presentation (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 sequencing 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 pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences 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 targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.

AB - 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 presentation (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 sequencing 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 pyelonephritis and asymptomatic bacteriuria isolates exhibited a similar total virulence gene count per isolate [median 18 (range 5–33) and 18 (5–30), respectively; P = 0.57] and for individual virulence genes differed significantly only for the prevalence of the pap operon (pyelonephritis 39%,versus asymptomatic bacteriuria 0%; P = 0.002). No other significant between-group differences 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 targeted therapies (e.g. vaccination or inhibitors of fimbrial adhesion) has yet to be studied.

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