Relationship Among Bacterial Virulence, Bladder Dysfunction, Vesicoureteral Reflux and Patterns of Urinary Tract Infection in Children
ABSTRACT We hypothesized that virulence levels of Escherichia coli isolates causing pediatric urinary tract infections differ according to severity of infection and also among various uropathies known to contribute to pediatric urinary tract infections. We evaluated these relationships using in vitro cytokine interleukin-6 elicitation.
E. coli isolates were cultured from children presenting with urinary tract infections. In vitro cytokine (interleukin-6) elicitation was quantified for each isolate and the bacteria were grouped according to type of infection and underlying uropathy (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary vesicoureteral reflux, no underlying etiology).
A total of 40 E. coli isolates were collected from children with a mean age of 61.5 months (range 1 to 204). Mean level of in vitro cytokine elicitation from febrile urinary tract infection producing E. coli was significantly lower than for nonfebrile strains (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no underlying etiology groups (p = 0.02).
In vitro interleukin-6 elicitation, an established marker to determine bacterial virulence, correlates inversely with clinical urinary tract infection severity. Less virulent, high cytokine producing E. coli were more likely to cause cystitis and were more commonly found in patients with neurogenic bladder and nonneurogenic bowel and bladder dysfunction, whereas higher virulence isolates were more likely to produce febrile urinary tract infections and to affect children with primary vesicoureteral reflux and no underlying etiology. These findings suggest that bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies.
[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE OF REVIEW: Recent guidelines on the management of urinary tract infections (UTIs) in children have seen a shift from aggressive imaging studies and the use of prophylactic antibiotics to a more restrictive and targeted approach. This review focuses on new additions to the literature on management of UTI from January 2011 to September 2012. RECENT FINDINGS: The causal relationship between UTI-vesicoureteral reflux (VUR) and renal scarring has been challenged by several studies. Concerns about unnecessary exposure to ionizing radiation, invasiveness of some of the procedures, and risk of infection have also been raised. With improved prenatal ultrasound, a 'top-down' approach to investigating febrile UTI in children using renal bladder ultrasound alone as an initial study has become popular. Several studies have reported that prophylactic antibiotics and imaging studies after first UTI can be reduced substantially without affecting the risk of recurrent UTI or renal scarring. SUMMARY: The use of targeted imaging approach in evaluating febrile UTI in children may lead to improved resource use and reduction of potential harmful procedures and interventions, without affecting outcomes of UTI in children. Providers using current guidelines should endeavor to collect practice-based evidence to validate and inform future guidelines.Current opinion in pediatrics 12/2012; DOI:10.1097/MOP.0b013e32835c14cc · 2.74 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1 (-/-) ) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1 (-/-) and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.PLoS ONE 10/2013; 8(10):e77714. DOI:10.1371/journal.pone.0077714 · 3.53 Impact Factor