261 ELUCIDATING MECHANISMS FOR RISK OF URINARY TRACT INFECTION WITH NEUROGENIC BLADDER

Abstract

You have accessJournal of UrologyPediatrics: Basic Research1 Apr 2011261 ELUCIDATING MECHANISMS FOR RISK OF URINARY TRACT INFECTION WITH NEUROGENIC BLADDER Zarine Balsara, Patrick Seed, and Sherry Ross Zarine BalsaraZarine Balsara Durham, NC More articles by this author , Patrick SeedPatrick Seed Durham, NC More articles by this author , and Sherry RossSherry Ross Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.352AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Neurogenic bladder (NB) poses an increased risk for urinary tract infections (UTI) and progressive renal damage. Currently, there are no successful strategies to reduce incidence of recurrent UTI (rUTI). With the aim of developing new therapeutics, we report the development of a model of experimental E. coli UTI in spinal cord injured (SCI) rats. We hypothesized that SCI rats would require lower inocula of E. coli to establish infection, have an exaggerated inflammatory response, and have delayed clearance of infection compared to normally voiding rats. METHODS Following a 2-week recovery period from T10 spinal cord transection or sham surgery, female Spraque-Dawley rats were transurethrally inoculated with 107–108 colony forming units (CFU) of the prototypic E. coli cystitis strain, UTI89. At 24h post-infection (hpi), urine, bladders, and kidneys were harvested and plated to enumerate CFU. Histopathology was performed to score inflammation. RESULTS T10 transection resulted in a NB phenotype with elevated residual urine volumes that stabilized at 2.4ml (range = 0.5ml-6.0ml) at 2 weeks post-injury. An inoculum of 107 CFU produced infection in 82% of SCI animals. SCI and control rats had statistically equivalent CFU in all samples (Table 1) and similar inflammatory infiltrates, predominated by neutrophils. Intracellular bacterial communities (IBC), which are collections of bacteria that serve as intracellular foci for rapid bacterial replication protected from the host inflammatory response and antibiotics, were also found in the bladder epithelium of both groups. This demonstrates that the SCI epithelium retains competence for intracellular replication by E. coli. Table 1:. Recovery of E. coli UTI89 from genito-urinary organs of SCI and control rats at 24hpi SCI rats Control rats CFU/ml-organ(GeometricMean) 95%CI(Lower,Upper) CFU/ml-organ(GeometricMean) 95%CI(Lower,Upper) p-value(Mann-Whitney) Urine 1.08×106 3.18×104,3.67×107 1.04×106 2.00×102,2.80×1010 0.9479 Bladder 6.38×105 9.42×103,4.32×107 9.73×105 2.00×102,1.42×1010 0.9480 RightKidney 9.18×104 3.07×103,2.75×106 5.88×104 2.00×102,3.24×108 1.0000 LeftKidney 9.38×103 6.55×102,1.34×105 5.49×104 2.00×102,3.96×108 0.4727 CONCLUSIONS These data suggest that SCI and control rats have similar susceptibility to initiating UTI with E. coli. Other mechanisms, such as differences in clearance or establishment of persistent intracellular bacterial reservoirs, may account for higher rates of rUTI in patients with NB. Ongoing studies will address differences in clearance of infection and differential inflammatory responses between SCI and control rats. These studies will elucidate underlying mechanisms for increased rates of rUTI in NB and lay the groundwork for new antibiotic-sparing preventative therapies. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e105 Peer Review Report Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zarine Balsara Durham, NC More articles by this author Patrick Seed Durham, NC More articles by this author Sherry Ross Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...