Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: a prospective study using whole-genome sequencing.

Abstract

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. 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. 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. 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.