By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Pyuria is common in asymptomatic children with neurogenic bladders, especially after bladder surgery. The simple presence of pyuria does not necessarily indicate a need for antibiotic treatment.

SOURCE: Su RR, Palta M, Lim A, Wald ER. Pyuria as a marker of urinary tract infection in neurogenic bladder: Is it reliable? Pediatr Infect Dis J 2019; Jun 20. [Epub ahead of print].

For children with neurogenic bladder due to myelomeningocele or other congenital abnormalities, urinary tract infection accounts for significant hospitalization and healthcare utilization. Unfortunately, there is not a consistent standard to guide the diagnosis of urinary tract infection in children with neurogenic bladders. Asymptomatic bacteriuria is common in this population, and the degree of pyuria is, at best, a controversial marker of urinary tract infection. Thus, the authors sought to determine the prevalence of pyuria in asymptomatic individual children with neurogenic bladders and how much the extent of pyuria varied over time. Presumably, if one knew the intensity of pyuria in asymptomatic children with neurogenic bladders, one would be better able to determine when pyuria is suggestive of an actual infection.

Potential study subjects were all children who enrolled in the spina bifida clinic at the University of Wisconsin from January 2004 through January 2015. There, the children underwent microscopic urine exams during each routine clinic visit. Symptoms were noted, and only samples taken from asymptomatic children were included. Thus, samples that coincided with fever, abdominal pain, abnormal urine odor, and altered urine function were excluded from the study. Researchers also excluded urine samples from the study if the patient received antibiotics for a presumed urinary tract infection during the two weeks before and after the time of sampling. When urine cultures were conducted, bacterial growth of more than 50,000 colony-forming units per milliliter was assumed to represent true bacteriuria. Investigators noted the use of intermittent catheterization and whether the child had undergone a surgical intervention that would introduce contact between the bladder and a usually non-sterile site (such as the creation of an appendiceal fistula for catheterization [Mitrofanoff procedure] or bladder augmentation).

The researchers included valid data for 305 urine samples from 50 different patients. Forty-eight of the patients had myelomeningocele, one had caudal regression syndrome, and one had cloacal exstrophy with a tethered spinal cord. Fourteen of the children had undergone surgical interventions.

Of the 305 urine samples, 70% contained fewer than five white blood cells per high power field. Of the total of 50 patients, 94% had at least one urine sample with less than five white blood cells per high power field. Sixteen patients had more than 50 white cells per high power field at least once and also had zero white cells at least once. Thus, there was a wide range of variability in the amount of pyuria, even within individual patients.

Age, gender, and whether the patient underwent routine intermittent catheterization were not significantly associated with pyuria, but a significant association occurred between pyuria and previous bladder surgery. More variability in the extent of pyuria occurred within a certain patient over time than occurred between different patients.

Overall, clinicians sent 36% of urine samples for bacterial culture; 75% of those were positive. Escherichia coli accounted for 48% of positive cultures. Klebsiella (23%) and gram-positive species (18%) were among the other bacteria isolated.

Thus, pyuria is common in asymptomatic children with neurogenic bladders and was seen in about 30% of samples. However, the presence and extent of pyuria varies significantly between, and especially within, individual patients at any given time. Significant bacteriuria also is fairly common, with about 27% of samples from these asymptomatic children showing growth of a pathogen.

COMMENTARY

Determining which children with neurogenic bladders actually have urinary tract infections that would benefit from treatment often can be difficult.1 A landmark study in 1995 followed urinary findings in asymptomatic children with neurogenic bladders without antibiotic treatment.2 Then, neither the presence of pyuria nor the finding of bacteriuria was associated with deterioration in renal function. An actual symptomatic infection developed in only a few cases.2 Now, the authors of this study have provided updated evidence that pyuria comes and goes in individual patients and is not necessarily indicative of a significant infection that requires antimicrobial treatment.

In a 2018 study of urine tests in children with neurogenic bladders (including symptomatic children), Enterococcus often was found in cultures even when pyuria or leukocyte esterase were not present in the urine.3 In that study, significant growth of Proteus usually was associated with the presence of both pyuria and leukocyte esterase. Pseudomonas was associated with leukocyte esterase positivity but not with pyuria.3 Thus, pyuria may be present with or without bacteriuria, and significant, even symptomatic, bacteriuria may be present even without pyuria.

Nearly two decades ago, asymptomatic children with neurogenic bladders who underwent routine intermittent catheterization were reviewed.4 Then, 81% of urine samples were abnormal: 51% with bacteriuria and pyuria, 26% with bacteriuria alone, and 5% with pyuria alone.4 Interestingly, interleukin-8 (IL-8) levels were elevated in 54% of the abnormal urine samples and in none of the normal samples; IL-8 was most likely to be elevated with pyuria.3 This prompted speculation that IL-8 was a marker for significant inflammation and, thus, for a true infection that might require antimicrobial treatment. Subsequently, elevated levels of urinary IL-8 were found to correlate with pyuria and bacteriuria in infected children,5 but it is not clear that IL-8 actually indicates that antimicrobial therapy would help asymptomatic patients with bacteriuria and/or pyuria.

What do clinicians do when faced with a child who has a neurogenic bladder and urinary findings? It depends. A recent scenario-based survey of hospitalists, nephrologists, and urologists revealed significant heterogeneity in how bacterial colonization (requiring no treatment) is distinguished from infection (and the need for antibiotic treatment).1 Although symptoms (incontinence between episodic catheterization, flank pain, fever) and urine findings (pyuria, heavy growth of a potential pathogen) tended to push toward considering the patient to be infected, broad variation occurred in both the diagnosis and the confidence with which the clinician made the diagnostic determination.1 The number of years in practice and the physician’s specialty accounted for some of the diagnostic variability.1

The authors have advanced knowledge by reminding us that pyuria is not necessarily abnormal in asymptomatic children with neurogenic bladders. For now, urinalyses are not needed to screen for urinary tract infection in asymptomatic children with neurogenic bladders. If for some reason pyuria is identified in an asymptomatic child, antibiotic treatment is not required. For children with symptoms of possible urinary tract infection, discretion is needed in interpreting clinical data.

REFERENCES

  1. Forster CS, Jackson E, Goldstein SL. Variation among subspecialists in the diagnosis of urinary tract infection in children with neurogenic bladders. J Pediatr Urol 2018;14:567.e1-567.e6.
  2. Schlager TA, Dilks S, Trudell J, et al. Bacteriuria in children with neurogenic bladder treated with intermittent catheterization: Natural history. J Pediatr 1995;126:490-496.
  3. Forster CS, Shaikh N, Hoberman A, Jackson E. Uropathogens and pyuria in children with neurogenic bladders. Pediatrics 2018;141:e20173006.
  4. Szucs K, O’Neil KM, Faden H. Urinary findings in asymptomatic subjects with spina bifida treated with intermittent catheterization. Pediatr Infect Dis J 2001;20:638-639.
  5. Zaki Mel S. Interleukin 8 is a surrogate marker for rapid diagnosis of bacteriuria. Immunol Invest 2008;37:694-703.