Is Pyuria Necessary to Diagnose Pediatric UTI?

Howard Uman, MD Pediatrician An Answer to Joe Breuner

 3-month-old female with fever >102, no localizing source.  Workup: UA (–), UC (+) >100,000 E coli  WBC 20, 75% PMN; blood culture (-),CRP 10 “10% of infants with have no pyuria”

 ? Early in course  ? Inadequate time to mild inflammatory response  ? “Immaturity of inflammatory response” Finding a reliable model…

 “diagnostic accuracy of the urinalysis for urinary tract in infants <3 months of age,” Shroeder, et al, pediatrics volume 135, #6, June 2015, PE. 965–971.  Sample: “True UTI”—urosepsis with (+)UC + (+)BC  (vs NOT “asymptomatic ”)  Invasion of renal parenchymabacterial multiply invade bloodstream  Damage occurs as a byproduct of the body’s own inflammatory response Findings from Schroeder, 2016

 “pyuria is a reliable finding in “true UTI”  Pyuria present in 96–99.5%  “UA sensitivity in bacteremic UTI is higher than previous reports in infants with UTI in general…”: >99% sensitivity for pyuria and/or LE  With UC(-): 87.8% LE (-) and WBC (-)  Previous studies promoted “faulty gold standards”—results skewed by inclusion of (+)UC caused by “contaminants or asymptomatic bacteriuria” Problem with Schroeder, 2016

 Definition of pyuria: >3 WBC/ high power field  Definition of (+) leukocyte esterase: “Any” ( trace–(1+)-(2+)-(3+) ) 2011 AAP guidelines

 Diagnosis of UTI based on pyuria and significant colony count in and “appropriately collected” urine specimen  Lowered threshold for (+)UC: 50,000 colonies of a recognized uropathogen  Pyuria definition: >5-10 WBC Questions remain

 What is the actual threshold for WBC in UA?  Cf: CSF, joint fluid Questions remain

 How reproducible is the UA?  Technique may effect the UA (semi quantitative)  Suggestion of “enhanced UA”: UA by hemocytometer Questions remain

 Correlation with acute phase reactants: CRP, pro calcitonin  Expect inflammatory markers should reflect invasive disease.  Compare UA results and acute phase reactants

 Use of DMSA scans to differentiate pyelonephritis vs asymptomatic bacteriuria What Schroeder, 2016 demonstrated

 A significant number of WBCs is usually present in bacteremic UTI/urosepsis  Noninflammatory bladder colonization (asymptomatic bacteriuria) exists in infants Parting thoughts

 Asymptomatic bacteriuria has been recognized since the 1970s  Treatment complicated the situation  RX temporary clearing recolonization, often with pathogens kidney damage J. Roberts, Peds 135, June, 2015,1126-1127 “The diagnosis of UTI: Liquid Gold and the Problem of a Gold Standards”  1956: >100,000 bact designated arbitrarily as dividing line, UTI vs colonization  1956–66: Adoption of 100,000 bacteria as gold standard; UA overlooked  1970s: Asymptomatic bacteriuria acknowledged; no morbidity  Treatment recognized as harmful  1999: Adjust culture threshold: > 50,000; adopted in 2011 AAP guideline  2016: What should be the threshold for WBC and LE in the UA?  2016: 10,000–50,000 significant with (+) UA (depending on organism?) references

 “association between uropathogen and pyuria” Shaikh, Peds 2016, p.1-5:  (+)UC less likely to exhibit pyuria with enterococcus, Klebsiella, Pseudomonas  need better biomarkers than WBC or LE to diagnose UTI

 “Reliability of UA for predicting UTI in young febrile children” Bachur, Arch Ped Adol Med 2001,p.60-65:  UA sensitivity 82%; UA specificity 92% (WBC>5; LE 1+)  T>38.5; M<1yo, F <2yo prevalence UTI 3.3% (Shaw); 2.1% (Bachur)  T>39: increased prevalence: F 5%; M 2.2% ( no data circ vs uncirc) references

 “screening for UTI in infants in the ER” Shaw, Peds 1998, p.1-5:  Enhanced UA (UA + gm stain) most sensitive, but 16% false positive.  (+) UA: 2+ LE or (+) nitrite

 “Dipstick screen for UTI in febrile infants” Glissmeyer, Peds, 2014, p.1121-27:  Dipstick compared favorably with microscopy, sating time and money

 “Enhanced UA screening for UTI in ED” Shah, Peds ID 2014, p. 272–5:  use of enhanced UA (hemocytometer + G-stain): Automated Uacomparable with manual UA for WBC; Gram stain superior for bacteria