B cell infiltration and lymphonodular hyperplasia in bladder submucosa of patients with persistent bacteriuria and recurrent urinary tract infections.

PURPOSE: We defined chronic inflammatory cell types in bladder submucosa and the presence of umbrella cells on the surface of bladder epithelium in patients 5 to 21 years old with persistent bacteriuria due to neurogenic bladder and recurrent urinary tract infections associated with vesicoureteral reflux. MATERIALS AND METHODS: Bladder mucosa biopsies from 12 patients and 6 controls were fixed in Carnoy's solution and examined for T cells (CD3, CD4, CD8), B cells (CD79) and plasma cells (CD138). The number of cells in a defined area of submucosa was determined by counting all nuclei in the area. A contiguous section was also stained for uroplakin expression with a monoclonal antibody against uroplakin III to ascertain the integrity of bladder umbrella cells. RESULTS: B cells, plasma cells and lymphoid nodules were found only in patient biopsies. T cell expression was evident in patient and control biopsies. Uroplakin staining of surface epithelium was uniform from control biopsies but spotty or entirely absent from patient biopsies. CONCLUSIONS: Patients with persistent bacteriuria or recurrent urinary tract infections had significant B cell infiltration in the submucosa, including lymphoid nodules. These inflammatory changes are likely due to antigenic stimulation from repeated exposure to bacteria. These changes are associated with frequent absence of uroplakin on surface epithelium.

Absence of bacterial reservoirs in the bladder epithelium of patients with chronic bacteriuria due to neurogenic bladder.

PURPOSE: Bacteriuria is common in patients with neurogenic bladder who are on clean intermittent catheterization for bladder emptying. In a longitudinal study patients carried 1 or 2 clones of Escherichia coli in the urine during months of surveillance. An explanation for persistent bacteriuria in this population could be that periurethral E. coli inoculated during clean intermittent catheterization would attach via type I adhesin, invade superficial bladder epithelial cells and establish reservoirs. Resurgence of bacteria from these reservoirs in bladder epithelium could later reenter the urine and establish a recurrent episode of bacteriuria. We investigated whether bacterial reservoirs were present in the superficial epithelium of patients with neurogenic bladder and chronic bacteriuria. MATERIALS AND METHODS: Bladder biopsies were obtained from patients with neurogenic bladder and a history of chronic recurrent bacteriuria. Biopsies were fixed in Carnoy's solution to preserve the material overlying the luminal surface of the superficial bladder epithelium. Following fixation biopsies were stained with hematoxylin and eosin to detect intracellular bacterial reservoirs and with periodic acid-Schiff for exopolysaccharide of biofilm. Fluorescence in situ hybridization was done to visualize individual bacteria. RESULTS: No evidence of bacterial reservoirs was found in the superficial bladder epithelium of 9 patients with neurogenic bladder. On hematoxylin and eosin staining epithelium with an intact luminal surface had no intracellular bacterial pods. On periodic acid-Schiff staining no biofilm or collection of exopolysaccharide surrounding bacterial communities was found. No collections or individual bacteria were seen on fluorescence in situ hybridization stained sections examined at 1,000x magnification with oil immersion. CONCLUSIONS: Bacterial reservoirs do not appear to be an important source of bacteriuria in patients with chronic recurrent bacteriuria due to neurogenic bladder.

Escherichia coli colonizing the neurogenic bladder are similar to widespread clones causing disease in patients with normal bladder function.

STUDY DESIGN: Clonal typing of neurogenic clones. OBJECTIVE: To determine whether neurogenic clones carried over weeks in the urine of asymptomatic children with neurogenic bladder were similar to known uropathogenic clones associated with disease. SETTING: Michigan State University; VA Medical Center, Minneapolis, MN, USA. METHODS: Escherichia coli isolates from the urine of 15 children previously followed were typed by multilocus sequence typing and compared to 2 human pyelonephritis genome strains, 29 pediatric or adult symptomatic urinary tract infection strains, 15 pediatric asymptomatic bacteriuria strains, 6 animal urinary tract infection strains and a neonatal meningitis-septicemia prototype K1 strain. Phylotypes and virulence genotypes were determined using PCR. RESULTS: Twenty-nine E. coli isolates were classified into 15 clones. Six of 15 clones were the same sequence type or a close relative to a clone that caused disease in a human or animal. These clones were considered uropathogens. The remaining nine clones were not closely related to a clone that caused disease and were considered commensal clones. Uropathogens were predominantly group B2, exhibited more virulence genes and were carried for more weeks in the neurogenic bladder compared to commensal clones. Nine of 15 children carried one or more uropathogenic clones; 4 children carried one or more commensal clones and 2 children carried both uropathogenic and commensal clones. CONCLUSION: Children with neurogenic bladder most commonly carried commensal clones. Uropathogenic clones were associated with prolonged carriage, however, carriage was not associated with symptomatic disease or deterioration of the upper urinary tract.

Effect of a phosphate supplement on urine pH in patients with neurogenic bladder receiving intermittent catheterization.

STUDY DESIGN: Pilot study; prospective design. SETTING: University Hospital, Virginia, USA. OBJECTIVE: To examine a phosphorus supplement as a urine-acidifying agent in patients with neurogenic bladder on clean intermittent catheterization. METHODS: Seven patients were followed for 4 weeks. For the first week of study urine pH was measured three times a day: first morning urine sample, afternoon sample, evening sample. For the second and third weeks urine pH was measured and the patients drank a phosphorus supplement three times a day. For the fourth week of study the patients did not take the phosphorus supplement but the measurement of urine pH was continued. The patients were visited in their homes twice a week. During each visit a sample of urine was collected for culture. A supplement container count was performed and urine pH recordings were checked. RESULTS: There was no significant change in urine pH during the 2-week period when a patient was on phosphorus supplementation compared to when the patient was off supplementation. In addition, urine acidification was not achieved over the time period when urine pH was monitored. CONCLUSION: Phosphate supplementation had no effect on urine pH in patients with neurogenic bladder.

Bladder epithelium is abnormal in patients with neurogenic bladder due to myelomeningocele.

OBJECTIVE: To describe the urothelium of the neurogenic bladder in patients with myelomeningocele on clean intermittent catheterization. SETTING: Outpatient practice. METHODS: Samples of bladder wall obtained from two groups of patients were examined for urothelium. The first group included 12 children and young adults with myelomeningocele and neurogenic bladder on intermittent catheterization for bladder emptying. The second group included eight children with vesicoureteral reflux and non-neurogenic bladder. Nine patients from the first group and four patients from the second group had urothelium. A contiguous section of each of the 13 samples with urothelium was stained for uroplakin expression, a marker of superficial bladder urothelium by immunohistochemistry. RESULTS: Samples from children with reflux revealed normal bladder epithelium and a uniform layer of umbrella cells (95% CI: 0-60%). In contrast, the epithelium from all patients with myelomeningocele was abnormal (95% CI: 66-100%). Epithelium from five patients (four children, one adult) revealed chronic inflammation. Three patients (two children, one adult) had squamous metaplasia. The apical surface of the epithelium in all patients with chronic inflammation had some reactivity with anti-uroplakin antibody, but the cells staining positive for uroplakin were scattered along the lumenal surface of the epithelium. The apical surface of patients with squamous metaplasia was negative for uroplakin. CONCLUSION: The urothelium of the neurogenic bladder in young patients with myelomeningocele is abnormal, with loss of uroplakin expression and altered urothelial proliferation.

Should we abandon standard microscopy when screening for urinary tract infections in young children?

Dipstick analysis is a screening test for urinary tract infection (UTI) in office practice. Standard urine microscopy is available offsite. We evaluated the usefulness of these tests on consecutive urine samples obtained by bladder catheterization in young children with a possible UTI. Thirty of 230 children had positive cultures. Dipstick analysis was specific (98%) but not sensitive (70%). Standard microscopy was not specific. Dipstick analysis and urine culture are useful tests for the diagnosis of UTI.

Effect of a single-use sterile catheter for each void on the frequency of bacteriuria in children with neurogenic bladder on intermittent catheterization for bladder emptying.

OBJECTIVE: The frequency of bacteriuria is high in children with neurogenic bladder on intermittent catheterization for bladder emptying. In an effort to decrease bacteriuria, we examined whether the method of catheter care was responsible for the high rate of bacteriuria. For this, the frequency of bacteriuria was examined in the same patient on single-use sterile catheters and on reused clean catheters. METHODS: A prospective, randomized, crossover trial was conducted with 10 patients who were randomized to 4 months of a new, sterile catheter for intermittent catheterization and 4 months of reuse of a clean catheter for intermittent catheterization. Each week, a urine sample was collected and symptoms of infection and medication use were recorded. RESULTS: A total of 158 urine samples were collected during 164 patient-weeks on the new catheter method for each void; 115 (73%) were positive for a pathogen. Of the 161 samples collected during 169 patient-weeks on the standard, reuse method for voiding, 123 (76%) were positive (115 [73%] of 158 vs 123 [76%] of 161). Escherichia coli was the most common pathogen detected during both method periods. CONCLUSION: A new, sterile catheter for each void did not decrease the high frequency of bacteriuria in patients with neurogenic bladder on intermittent catheterization.

Urinary tract infections in children younger than 5 years of age: epidemiology, diagnosis, treatment, outcomes and prevention.

Although the true incidence of urinary tract infections (UTIs) in children is difficult to estimate, they are one of the most common bacterial infections seen by clinicians who care for young children. Except for the first 8 to 12 weeks of life, when infection of the urinary tact may be secondary to a haematogenous source, UTI is believed to arise by the ascending route after entry of bacteria via the urethra. Enterobacteriaceae are the most common organisms isolated from uncomplicated UTI. Infection with Staphylococcus aureus is rare in children without in-dwelling catheters or other sources of infection, and coagulase-negative staphylococci and Candida spp. are associated with infections after instrumentation of the urinary tract. The diagnosis of UTI in young children is important as it is a marker for urinary tract abnormalities and, in the newborn, may be associated with bacteraemia. Early diagnosis is critical to preserve renal function of the growing kidney. A urine specimen for culture is necessary to document a UTI in a young child. Prior to culture, urinalysis may be useful to detect findings supporting a presumptive diagnosis of UTI. The goals of the management of UTI in a young child are: (i) prompt diagnosis of concomitant bacteraemia or meningitis, particularly in the infant; (ii) prevention of progressive renal disease by prompt eradication of the bacterial pathogen, identification of abnormalities of the urinary tract and prevention of recurrent infections; and (iii) resolution of the acute symptoms of the infection. Delay in initiation of the antibacterial therapy is associated with an increased risk of renal scarring. The initial choice of antibacterial therapy is based on the knowledge of the predominant pathogens in the patient's age group, antibacterial sensitivity patterns in the practice area, the clinical status of the patient and the opportunity for close follow-up. Imaging studies to detect congenital or acquired abnormalities are recommended following the first UTI in all children aged <6 years. Patients with significant urinary tract abnormalities and/or frequent symptomatic UTI may benefit from prophylactic antibacterials. The main long term consequence of UTI is renal scarring which may lead to hypertension and end-stage renal disease. Prevention of recurrent UTI focuses on detection, and correction if possible, of urinary tract abnormalities. Interventions that have been associated with a decrease in symptomatic UTI in children with a history of recurrent UTI include relief of constipation and voiding dysfunction.

Expression of virulence factors among Escherichia coli isolated from the periurethra and urine of children with neurogenic bladder on intermittent catheterization.

BACKGROUND: Patients with neurogenic bladder caused by spinal cord injury or myelomeningocele empty their bladder several times a day by intermittent catheterization. Bacteriuria without symptoms of infection is frequently present in these patients. Occasionally a clone of Escherichia coli that has been carried for weeks without symptoms causes a symptomatic urinary tract infection. Virulence factors are commonly expressed among E. coli causing infection in patients with normal urinary tracts. However, it is unknown whether expression of virulence factors by an E. coli clone colonizing the neurogenic bladder increases the risk of subsequent infection. In this study we examined the prevalence of virulence factor expression among E. coli isolated from the periurethra and urine of patients with neurogenic bladder. METHODS: The prevalence of virulence factors was examined among E. coli isolated from the periurethra and urine in patients with neurogenic bladder who received intermittent catheterization and were followed for 6 months. Representative isolates from the 37 clonal types of E. coli detected in the periurethra and urine of children with neurogenic bladder were assessed for O antigen, hemolysin, aerobactin, serum resistance and type I and P-adhesin. RESULTS: All clones were serum-resistant and expressed type I adhesin, none expressed aerobactin and two expressed hemolysin. The presence of P-adhesin was not unique to clones associated with symptomatic infection. The presence of P-adhesin carried for weeks in a clone did not predict subsequent infection in the neurogenic bladder. CONCLUSION: Bacterial virulence factors did not predict infection of the neurogenic bladder.

Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization.

OBJECTIVE: To determine the effect of cranberry prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with neurogenic bladder receiving clean intermittent catheterization. DESIGN: Double-blind, placebo-controlled, crossover study of 15 children receiving cranberry concentrate or placebo concentrate for 6 months (3 months receiving one concentrate, followed by 3 months of the other). Weekly home visits were made. During each visit, a sample of bladder urine was obtained by intermittent catheterization. Signs and symptoms of urinary tract infection and all medications were recorded, and juice containers were counted. RESULTS: During consumption of cranberry concentrate, the frequency of bacteriuria remained high. Cultures of 75% (114 of 151) of the 151 samples obtained during consumption of placebo were positive for a pathogen (>/=10(4) colony-forming units/mL) compared with 75% (120 of 160) of the 160 samples obtained during consumption of cranberry concentrate. Escherichia coli remained the most common pathogen during placebo and cranberry periods. Three symptomatic infections each occurred during the placebo and cranberry periods. No significant difference was observed in the acidification of urine in the placebo group versus the cranberry group (median, 5.5 and 6.0, respectively). CONCLUSION: The frequency of bacteriuria in patients with neurogenic bladder receiving intermittent catheterization is 70%; cranberry concentrate had no effect on bacteriuria in this population.

Detection of group A streptococci in children under 3 years of age with pharyngitis.

OBJECTIVE: To determine the frequency of group A streptococcal pharyngitis in young preschool children presenting to the emergency department with upper respiratory tract infection. METHODS: A prospective, observational study performed between September 1995 and September 1997. Throat swabs were obtained on young children less than 3 years old with pharyngeal erythema as well as age- and time-matched controls without pharyngeal erythema or exudate. Signs and symptoms that were recorded included: age, temperature, pharyngeal erythema, tonsillar exudate, cervical adenopathy, scarlatini-form rash, rhinorrhea, school-aged child in the home, day care attendance. Swabs were inoculated on 5% sheep blood agar and incubated for 48 hours. Beta-hemolytic colonies were sero-grouped by latex agglutination. RESULTS: Seventy-eight children with pharyngeal erythema, and 152 controls had pharyngeal specimens obtained and signs or symptoms recorded. Under 2 years of age, the detection of group A streptococci was similar to controls. Detection of group A streptococci was significantly different from controls in children over 2 years of age. Ten (29%) of 35 children over 2 years were positive for group A streptococci compared to 2 (7%) of 29 controls of the same age group (P = 0.03, odds ratio 5, 95% CI: 1.2-24). Findings on clinical examination in children with pharyngeal erythema did not distinguish those that would be culture-positive for group A streptococci. CONCLUSION: In our emergency department, group A streptococci caused 30% of pharyngitis seen in children between 2 and 3 years of age. Diagnostic testing is recommended because physical examination may not accurately distinguish etiology in this age group.

Group A streptococcal pharyngitis in adults 30 to 65 years of age.

BACKGROUND: Although the frequency of group A streptococcal pharyngitis in adults is assumed to be low, there is little information on frequency other than in military populations. METHODS: A prospective, observational study was done to determine the frequency of group A streptococcal pharyngitis in adults seen in the emergency department. Throat swabs were obtained on adults (30 to 65 years of age) with sore throat and pharyngitis on examination. Swabs were also obtained in a group of control subjects. RESULTS: Of the 148 adults with pharyngitis, 65 (44%) had throat specimens positive for group A streptococci. In the 50 control subjects, all throat cultures were negative for group A streptococci. A significant number of patients with group A streptococcal pharyngitis had school-aged children at home. CONCLUSION: The high rate of detection of group A streptococci in adults outside the military has not been previously reported.

Correlation of periurethral bacterial flora with bacteriuria and urinary tract infection in children with neurogenic bladder receiving intermittent catheterization.

Periurethral bacteria are inoculated daily into the urine of children with neurogenic bladder during clean intermittent catheterization (CIC). We examined how frequently periurethral bacterial species produced bacteriuria in children followed longitudinally. When Escherichia coli was detected on the periurethra, bacteriuria was also present 93% of the time. When Klebsiella, Pseudomonas, or Enterococcus species or nonpathogens were detected on the periurethra, bacteriuria was present 80%, 40%, 40%, and 25% of the time, respectively. Clonal typing of multiple colonies of E. coli from each periurethral and urine culture revealed that children carried only one or two E. coli clones in their urinary tracts over months of surveillance. When E. coli was detected in the urine, the identical clone was on the periurethra. E. coli persisted for weeks in the urine without causing symptoms. Occasionally the same E. coli clone carried for weeks caused a urinary tract infection. Bacteriuria frequently occurs after inoculation of periurethral E. coli into the urine during CIC.

Nitrofurantoin prophylaxis for bacteriuria and urinary tract infection in children with neurogenic bladder on intermittent catheterization.

OBJECTIVE: To determine the effect of nitrofurantoin prophylaxis on rates of bacteriuria and symptomatic urinary tract infection in children with chronic neurogenic bladder receiving clean intermittent catheterization. DESIGN: Double-blind, placebo-controlled, crossover trial of 15 children receiving nitrofurantoin or placebo for 11 months (5 months receiving one drug, then 1 month of washout followed by 5 months of the alternate drug). Weekly home visits were made. During each visit a sample of bladder urine was obtained by intermittent catheterization, signs and symptoms of urinary tract infection were recorded, and all medications were recorded as well as a capsule count of the study drug. RESULTS: During nitrofurantoin the frequency of bacteriuria remained high. Cultures of 74% (203 of 274) of the 274 samples on placebo were positive for a pathogen (> or = 10(4) colony-forming units per milliliter) compared with 65% (165 of 252) of the 252 samples on nitrofurantoin. The bacterial species responsible for bacteriuria, however, were altered; Escherichia coli, the most common pathogen isolated during placebo, was replaced by resistant Klebsiella spp. and Pseudomonas spp. during nitrofurantoin. The carriage of these resistant organisms tripled during nitrofurantoin. Symptomatic infection dropped in half on nitrofurantoin, but this decline was due solely to infections caused by E. coli. Despite an increased frequency of resistant organisms on nitrofurantoin prophylaxis, an increase in urinary tract infections caused by these resistant organisms did not occur. CONCLUSION: Routine use of nitrofurantoin prophylaxis in an attempt to eradicate bacteriuria in patients with chronic neurogenic bladder is not effective.

Intravascular catheter colonization in critically ill children.

In a prospective study, cultures were obtained of all intravascular catheters removed from children in an intensive care unit. Of 366 catheters removed from 217 children, 110 (30%) were found to be colonized, most commonly with coagulase-negative staphylococci. Despite the high rate of colonization, there were only nine instances (2%) of catheter-related bacteremia.

The ability of periurethral Escherichia coli to grow in a voiding system is a key for the dominance of E. coli cystitis.

The generally accepted concept of the pathogenesis of cystitis is that bacteria on the periurethra migrate via the urethra to the bladder urine. To explore why Escherichia coli is the dominant organism isolated from cystitis, we examined two potential mechanisms that might account for the dominance of E. coli as the etiologic agent in cystitis in prepubertal, non-sexually active girls. First, the frequency of carriage of aerobic bacteria on the periurethra of two populations-healthy girls and girls after their first episode of cystitis was determined. Second, the survival capability of periurethral bacteria in urine under voiding conditions was examined. Two voids were simulated over 6 h by 10(2) dilution. A control was run in broth instead of urine. We found that Gram-positive bacteria, particularly coagulase-negative staphylococci, were much more common on the periurethra than E. coli. E. coli did grow well in urine in an in vitro voiding system whereas most Gram-positive bacteria did not. Growth in urine despite voiding may be the key reason for the dominance of E. coli in cystitis.

Optical immunoassay for rapid detection of group A beta-hemolytic streptococci. Should culture be replaced?

OBJECTIVE: To evaluate an optical immunoassay rapid antigen test to detect group A beta-hemolytic streptococci directly from throat swab specimens. DESIGN: Criterion standard with "blinded" comparison. Double-swab pharyngeal samples were obtained; one swab was cultured and the other was used for the rapid antigen test. SETTING: Microbiology laboratory in a primary care center at a university teaching hospital. PATIENTS: Two hundred sixty-two outpatients with pharyngitis. MAIN OUTCOME MEASURE: The results of the optical immunoassay rapid antigen test were compared with results of standard aerobic culture. RESULTS: Sixty-two (24%) of 262 samples were culture-positive; 48 of these 62 were positive by the optical immunoassay rapid test (sensitivity, 77%). Of the 200 culture-negative samples, seven (4%) were positive by the rapid test (specificity, 96%). CONCLUSION: The optical immunoassay performed well, but like other rapid tests, is not sensitive enough to replace standard culture for detection of group A beta-hemolytic streptococci.