In the JournalsPerspective

Current guidelines may lead to untreated UTIs in children

Nader Shaikh

Study findings published in The Journal of Pediatrics suggest that following current guidelines for the diagnosis of UTI in children may result in many children with a UTI going untreated, researchers said.

A systematic review and meta-analysis found that the prevalence of asymptomatic bacteriuria (ABU) is “considerably lower” than the prevalence of UTI in most children aged 19 years or younger, the researchers reported.

Although some clinicians are concerned that children who present with ABU and develop a non-localizing febrile illness may be mistakenly diagnosed with a UTI, the researchers said the low prevalence of ABU noted in this study means this will occur “extremely rarely” — suggesting a need to revise AAP guidelines.

“The current guidelines require pyuria or leukocyte esterase to be present when diagnosing a UTI,” Nader Shaikh, MD, MPH, professor of pediatrics at the University of Pittsburg School of Medicine and Children’s Hospital of Pittsburgh, told Healio. “This requirement probably does more harm than good. Had the prevalence of ABU been high relative to the prevalence of [UTI], then this requirement may have benefited children.”

Shaikh estimated that, under current guidelines, for every child with ABU who is not given antibiotics, 12 children with febrile UTI risk going untreated. The CDC recommends against antibiotic treatment for asymptomatic bacteriuria in children and requires urinalysis suggestive of infection with presence of pyuria, nitrites or bacteriuria for a diagnosis of pediatric UTI.

Shaikh and colleagues included 14 studies in their review with data on bacteriuria in 49,806 asymptomatic children aged 19 years or younger who had urine collected via bladder catheterization, bladder aspiration or three consecutive clean catch samples.

ABU prevalence in the studies was 0.47% in girls (95% CI, 0.36%-0.59%) and 0.37% in boys (95% CI, 0.09%-0.82%), with corresponding values for ABU without pyuria of 0.38% (95% CI, 0.22%-0.58%) and 0.18% (95% CI, 0.02%-0.51%), respectively, according to Shaikh and colleagues.

ABU prevalence was previously assumed to be between 1% and 2% on average, Shaikh said, an assumption based primarily on screening programs from the 1950s and 1960s.

“Even though many of these screening programs were aimed at detecting urinary tract infection, and thus included symptomatic children, those with bacteriuria detected in these studies came to be referred to as children with ‘asymptomatic bacteriuria,’” he said.

Circumcised boys aged 1 year or younger and girls aged 2 years or older were the subgroups with the highest ABU prevalence. The prevalence of ABU in boys following infancy was 0.08% (95% CI, 0.01%-0.37%). Median duration of ABU in untreated boys and girls was found to be 1.5 and 2 months, respectively, in the one study that included this outcome.

“Pyuria and leukocyte esterase are not always present in children with UTI. Requiring it will lead to missed UTIs,” Shaikh said. “Until better biomarkers are available, febrile infants should receive the gold standard test for UTI, which is the urine culture. Although a small number of children with ABU may be incorrectly diagnosed with a UTI as a result, this number is far less than the number of children with UTI that are being missed using our current definition of UTI.” – by Eamon Dreisbach

Reference:

CDC. Pediatric Treatment Recommendations. https://www.cdc.gov/antibiotic-use/community/for-hcp/outpatient-hcp/pediatric-treatment-rec.html. Accessed Dec. 12, 2019.

Shaikh N, et al. J Pediatr. 2019;doi:10.1016/j.jpeds.2019.10.019.

Disclosures: The authors report no relevant financial disclosures.

Nader Shaikh

Study findings published in The Journal of Pediatrics suggest that following current guidelines for the diagnosis of UTI in children may result in many children with a UTI going untreated, researchers said.

A systematic review and meta-analysis found that the prevalence of asymptomatic bacteriuria (ABU) is “considerably lower” than the prevalence of UTI in most children aged 19 years or younger, the researchers reported.

Although some clinicians are concerned that children who present with ABU and develop a non-localizing febrile illness may be mistakenly diagnosed with a UTI, the researchers said the low prevalence of ABU noted in this study means this will occur “extremely rarely” — suggesting a need to revise AAP guidelines.

“The current guidelines require pyuria or leukocyte esterase to be present when diagnosing a UTI,” Nader Shaikh, MD, MPH, professor of pediatrics at the University of Pittsburg School of Medicine and Children’s Hospital of Pittsburgh, told Healio. “This requirement probably does more harm than good. Had the prevalence of ABU been high relative to the prevalence of [UTI], then this requirement may have benefited children.”

Shaikh estimated that, under current guidelines, for every child with ABU who is not given antibiotics, 12 children with febrile UTI risk going untreated. The CDC recommends against antibiotic treatment for asymptomatic bacteriuria in children and requires urinalysis suggestive of infection with presence of pyuria, nitrites or bacteriuria for a diagnosis of pediatric UTI.

Shaikh and colleagues included 14 studies in their review with data on bacteriuria in 49,806 asymptomatic children aged 19 years or younger who had urine collected via bladder catheterization, bladder aspiration or three consecutive clean catch samples.

ABU prevalence in the studies was 0.47% in girls (95% CI, 0.36%-0.59%) and 0.37% in boys (95% CI, 0.09%-0.82%), with corresponding values for ABU without pyuria of 0.38% (95% CI, 0.22%-0.58%) and 0.18% (95% CI, 0.02%-0.51%), respectively, according to Shaikh and colleagues.

ABU prevalence was previously assumed to be between 1% and 2% on average, Shaikh said, an assumption based primarily on screening programs from the 1950s and 1960s.

“Even though many of these screening programs were aimed at detecting urinary tract infection, and thus included symptomatic children, those with bacteriuria detected in these studies came to be referred to as children with ‘asymptomatic bacteriuria,’” he said.

Circumcised boys aged 1 year or younger and girls aged 2 years or older were the subgroups with the highest ABU prevalence. The prevalence of ABU in boys following infancy was 0.08% (95% CI, 0.01%-0.37%). Median duration of ABU in untreated boys and girls was found to be 1.5 and 2 months, respectively, in the one study that included this outcome.

“Pyuria and leukocyte esterase are not always present in children with UTI. Requiring it will lead to missed UTIs,” Shaikh said. “Until better biomarkers are available, febrile infants should receive the gold standard test for UTI, which is the urine culture. Although a small number of children with ABU may be incorrectly diagnosed with a UTI as a result, this number is far less than the number of children with UTI that are being missed using our current definition of UTI.” – by Eamon Dreisbach

Reference:

CDC. Pediatric Treatment Recommendations. https://www.cdc.gov/antibiotic-use/community/for-hcp/outpatient-hcp/pediatric-treatment-rec.html. Accessed Dec. 12, 2019.

Shaikh N, et al. J Pediatr. 2019;doi:10.1016/j.jpeds.2019.10.019.

Disclosures: The authors report no relevant financial disclosures.

    Perspective

    As a pediatric urologist, I am frequently asked to give lectures on pediatric UTIs. It is always very humbling as ‘the expert’ to admit to the audience that I do not know the definition of a UTI. In fact, the definition of UTI varies across time and space. 

    Different countries follow different organizations’ guidelines, which have different urine culture colony-forming unit (CFU) cutoffs for making the diagnosis of a UTI. These cutoffs also vary depending on the differently recommended techniques of obtaining the urine sample (ie, voided, catheterization, suprapubic aspiration). Over time, the AAP changed its definition of a UTI in children aged 2 to 24 months. The most recent AAP definition reduced the culture results cutoff from 100,000 CFU/mL to 50,000 CFU/mL but at the same time introduced a requirement for having pyuria. The thought process behind this was that a true infection as opposed to asymptomatic bacteriuria should cause some form of host response identified by pyuria on urinalysis. By restricting the definition of a UTI in this manner, the logic was that fewer children with harmless asymptomatic bacteriuria would be misdiagnosed as having a UTI and subjected to unnecessary treatment with antibiotics.

    Shaikh and colleagues’ meta-analysis demonstrates that the prevalence of asymptomatic bacteriuria and asymptomatic bacteriuria with pyuria is at least an order of magnitude less than the prevalence of UTI. With these findings, the authors of the study make the valid point that it is a rare situation when a child with harmless asymptomatic bacteriuria would be diagnosed with a UTI. For this to happen, a preverbal child would need to have developed a febrile illness with nonspecific symptoms and have a urine sample collected that demonstrates no pyuria but a positive urine culture. 

    Going further, the authors make the point that since the prevalence of asymptomatic bacteriuria is very low relative to the prevalence of UTIs, it is much more likely that among febrile preverbal children being tested for UTI, those with a true UTI will have a negative leukocyte esterase test and, therefore, the diagnosis of a UTI would be missed. The authors estimate that as a result of the AAP’s change in the definition of UTI, up to 12 children with true UTIs are being missed to protect one child with asymptomatic bacteriuria from receiving unnecessary antibiotics. Ultimately, this translates into children with pyelonephritis not receiving timely antibiotics, which increases the risk of kidney damage. and therefore, more harm than good is likely to be done by the requirement of a positive leukocyte esterase urinalysis test. 

    Life was simpler when we falsely believed that urine was sterile. We now know this isn’t the case and that there is even a urinary microbiota. Although on a superficial level the logic behind the AAP’s requirement for a positive urinalysis to better define when bacteriuria becomes a UTI makes sense, the data from this and other studies show this is too simplistic. There are indeed children with a UTI and pyelonephritis who will have a negative urinalysis. In fact, multiple studies have demonstrated leukocyte esterase test is less likely to be positive when the uropathogenic organisms are Enterococcus, Klebsiella or Pseudomonas. A better urine test or marker is needed to help differentiate children with a UTI from those with asymptomatic and harmless bacteriuria. Unfortunately, in the meantime, clinicians cannot, and should not, rely on the urinalysis alone to rule out a UTI.

    • Christopher S. Cooper, MD, FACS, FAAP
    • Tyrone D. Artz Chair in Urology
      Professor and Vice Chairman of Urology
      University of Iowa, Carver College of Medicine

    Disclosures: Cooper reports no relevant financial disclosures.