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UTI Without Pyuria

Nader Shaikh, MD, Michael Cosimini, MD, and Solomon Behar, MD
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Tags pyuria · UTI

Dr Cosimini and Dr Shaikh discuss UTI’s and pyuria. Circumcised males, Hispanic children, children without fever and children with grades 3 and 4 vesicoureteral reflux were more likely to have a UTI caused by organisms other than E. coli.

 

Pearls:

  • In a recent retrospective review of urinary tract infections diagnosed in the emergency room 13% of children with clinical symptoms consistent with UTI and a positive urine culture did not have pyuria.

  • Pyuria was less likely to be present in infections caused by Enterococcus or Klebsiella.

  • New biomarkers to detect urinary tract infection are being developed and will hopefully improve our diagnostic ability going forward.

 

Case

A nine-month-old white girl presents with fever for 2 days in the absence of other symptoms. The physical exam does not reveal a source of fever. Urinalysis(UA) and microscopy do not show signs of infection. The child is sent home and two days later the culture comes back as greater than 100,000 colony forming units of enterococcus. Does this child have a urinary tract infection (UTI)?

 
  • The 2011 American Academy of Pediatrics(AAP) guidelines state that  “To establish the diagnosis of UTI, clinicians should require both urinalysis results that suggest infection (pyuria and/or bacteriuria) and the presence of at least 50,000 colony-forming units (CFUs) per mL of a uropathogen cultured from a urine specimen obtained through catheterization or super pubic aspiration.”

  • Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011 Sep;128(3):595-610 PMID: 21873693

  • A recent study by Dr. Shaikh challenges the need for pyuria to establish the diagnosis of UTI.  The study is a retrospective review of UTIs diagnosed by culture in children with clinical symptoms suggestive of urinary tract infection in the University of Pittsburgh Emergency Department and evaluates which patients and pathogens are found to be associated with pyuria. Thirteen percent of these children with positive cultures and clinically consistent symptoms did not have pyuria by dipstick UA or microscopy.

 

Shaikh N et al. Association Between Uropathogen and Pyuria. Pediatrics. 2016 Jul;138(1). PubMed PMID: 27328921

 
  • Why is an abnormal urinalysis or microscopy part of the guidelines in the first place? The AAP probably was looking to reduce the excessive use of antibiotics for patients with positive cultures who did not really have  a UTI.

  • Going back through five years of cultures you found that pyuria was absent in 13% of these children that symptomatically and by culture seem to have UTI. Was this a surprising finding? This finding is consistent with the previous literature including a 2010 meta-analysis that found that rapid tests are negative for around 10% of children with urinary tract infections.

  • Williams GJ et al. Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis. Lancet Infect Dis. 2010 Apr;10(4):240-50. PMID: 20334847

  • One thing that stood out to me in your data was the breakdown by age. I had been taught to not trust the UA in the youngest children. This I believe is partially because it takes time for dietary nitrate to be metabolized by bacteria in the bladder to nitrite but I also expected to see a difference in the presence of white blood cells(WBCs). What difference did you see in those younger and older than two months of age? There was no difference in the frequency of pyuria in children with urinary tract infections between these two age groups. Some older data had suggested that it may be less common in those less than six-months of age but this study and other more recent studies have not shown this.

  • The most common pathogen is UTI and we saw bacteria often did elicit pyuria, which pathogens did not? Enterococcus and Klebsiella were both statistically significantly less likely to be associated with pyuria. Pseudomonas appeared to be less likely to be associated with pyuria but few cases were seen. An early hypothesis was the gram positive organisms would be less pyogenic but this did not seem to be the case. Biofilms were another consideration but bacteria that form these were found in both groups. Different bacteria seem to produce different degrees of inflammatory response.

  • What can we clinically take home from this study? While the urinalysis is a very good test we cannot trust it alone. If we catheterize a child for urine we should send the urine for culture even if the urinalysis is normal.

  • If I have really high suspicion for UTI could it be reasonable to treat empirically even in the face of a negative UA given this data? In a pre-verbal child it would be very difficult to get your pre-test probability to a point where you could decide to treat. Shaikh does not empirically treat patients with a negative UA.

Anything else we should discuss? Adding pyuria to the definition of UTI does increase the specificity of the diagnosis but at the cost of missing cases. Adding tests together does not solve the problem of the limitations of the test. What we need is new testing methods including urinary biomarkers that can improve our diagnostic ability. Studies to find better biomarkers are ongoing and hopefully will get us something we can use.

Roy B., MD -

Nice summary of an interesting study!

However, I have some misgivings about the conclusions. The authors seem to have disregarded the concept of asymptomatic bacteruria, redefining a UTI based only on culture counts. They probably have a point (that at least some true UTIs lack pyuria), but lacking a "gold standard" to determine a true UTI means that it's not meaningful to compare diagnosis by culture versus diagnosis by culture + UA. Which one is correct? There can be no objective measure of sensitivity or specificity unless you compare against an established gold standard. I think their conclusion -- that culture alone is better than the currently recommendation of culture + abnormal UA -- is not supported by their study, because they didn't actually show that their "culture pos/UA neg "UTIs"" were in fact UTIs. They needed a treatment arm or some other confirmation that their UTIs were true UTIs in order to reach that conclusion.

Michael C. -

Thanks for commenting Roy. I agree that this is a challenge for a study like this. Especially in a retrospective design.

How often does asymptomatic bacteruria really occur in such a population as to confound these results? An older study that did screening for this in asymptomatic Swedish infants with a bag/reflex SPA method (unfortunately with some lag between samples). They find it to be a fairly rare occurrence 0.17 to 0.79% of specimens in those over 2 months of age depending on age and gender. This may not be an insignificant percentage when we look at a study of 26,000 urine samples but in a given patient with fever, bacteruria and no other source I am still not holding back on the basis of a negative UA.

About half of these had pyuria as well which I think raises further questions.

Wettergren B, Jodal U, Jonasson G. Epidemiology of bacteriuria during the
first year of life. Acta Paediatr Scand. 1985 Nov;74(6):925-33. PubMed PMID:
4090969.

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