1. Lab Rounds: Diagnosis of Pediatric UTI’s Chris McCrossin

2. Outline To Review methods of urine collection Sensitivity, specificity, and clinical use of: –Urinalysis –Microscopy –Culture

3. Case 1: Methods of Collection 18 m/o F presents with one day history of fever and one episode of vomiting; otherwise well looking child No clear focus of infection you want to rule out UTI How do you collect the urine?

4. Collection Options Infants and Non-toilet trained children Possibilities for collection –Catheter specimen –Suprapubic (gold standard) –Bagged specimen –Clean catch

5. Bag Specimen vs Clean Catch Best evidence topic report in EMJ 2006 Authors found two relevant papers between 1966 and 2005 Disclaimer: The following discussion is to look at the use of bag specimens and dip to screen who needs to be catheterized. Bagged specimens should never be sent for culture

6. Bag Specimen vs Clean Catch Alam et al 2005 191 children <3 yrs of age (125 were boys) All had attempts at clean catch and urine bag sampling Looked at bacterial contamination: »14.7% contamination with clean catch »26.6% contamination with bag specimen

7. Bag Specimen vs Clean Catch Hardy et al 1976 30 unwell children with suspected UTI Compared clean catch with bag and suprapubic aspiration of urine Results: »Bag specimens 4/30 pure growth, 22/30 contaminated »Clean catch 2/30 pure growth, 22/30 contaminated

8. Bag Specimen vs Clean Catch According to their “best evidence” review there is one paper (with significant weaknesses) that suggests clean-catch is a better non-invasive technique when compared with bag specimens

9. Bag vs Catheter McGillivray et al 2005 compared the use of bag versus catheter urinalysis in children under 3 “at risk for UTI” Results: Urine Dip »Bag 85% sensitive, 62% specific »Cath 71% sensitive, 97% specific »Neonates <90 days old had sensitivity of 69% for bag, 46% for cath

10. Bag vs Cath Authors conclude that although small sample size of infants, the low sensitivity of dip regardless of collection technique requires the culture of a catheter specimen in the under 90 day old age group Dipstick will miss 4-12% of UTI’s in this age group

11. Bag vs Cath Authors also suggest: “children with fever without source at low risk for UTI (no previous history of UTI, no anatomic abnormalities, not immunosuppressed, no urinary symptoms), a selective cath strategy as outlined in the AAP practice parameter appears reasonable” A reduction of catheterizations of 46% in non-toilet trained peds older than 90 days (reduction potentially even greater in a population with lower rate of UTI’s than in their study population

12. Questions for you Is it practical in a busy emerg to use bags or clean catch urines for screening who needs catheterization? Are we able to accurately assess who is at “low risk” for UTI in emerg?

13. In and Out Cath Cons: Invasive May need to do it several times to get urine Chance of introducing infection Chance of urethral trauma Pros Next best method after suprapubic cath in terms of avoiding a contaminated specimen

14. Use of Ultrasound in Urethral Catheterization Lei et al 2005 published in Pediatrics Prospective study using bedside U/S pre-cath to determine urine bladder volume in ages 0- 24 months Methods: »2 phases »1st phase: immediate cath in 136 patients »2nd phase: initial scanning in 112 patients prior to cath

15. Use of Ultrasound in Urethral Catheterization Results: –Initial phase: 72% success rate with initial catheterization –Intervention phase: »Sufficient urine identified in 76% with a success of first cath in 98% of those patients »Patients without sufficient urine were rescanned every 1/2 hour with all showing enough urine within 90 minutes. 93% underwent initial successful catheterization »Overall successful first cath in intervention phase was 96% Authors conclude able to avoid repeated cath with a safe non invasive procedure

16. AAP Recommendations Aspiration or urethral catheterization to establish a diagnosis of UTI in neonates and young children if antibiotics required In an infant or child 2 months to 2 years of age with unexplained fever not so ill as to require immediate antimicrobial therapy there are two options: –Obtain culture by SPA or cath –Perform urinalysis by most convenient means. If suggestive of UTI then do a cath/SPA. If cath urinalysis - then watch over time

17. Next Case: So now you have a 4 month old F patient who is febrile, no specific UTI risk factors, and normal R&M Do you send for culture? Would it make a difference if she was 3 years old and had burning with urination?

18. Urine Dip in Pediatric Population Overall has a sensitivity of 80% Prevalence of UTI is estimated at 5% Rate of UTI in a negative urinalysis is expected to be about 1.3% »Newman, Takayama: Urinary tract controversy and questions (letter). Pediatrics 101:731-732

19. Urine Dip Components: Leukocyte esterase Positive results from presence of significant leukocytes in the urine Anything that gives pyuria can result in a positive test A negative test result coupled with a lack of urinary symptoms is usually sufficient to rule out UTI »Liao et al 2001 Ped Clinics NA

20. Urine Dip Components: Nitrites Gram-negative rods (ie E Coli) contain the enzyme nitrate reductase (NR) This enzyme converts dietary nitrate in the urine to nitrite Causes of False Negatives: »Inadequate dietary nitrate »Bacteria lacking NR »Urine samples not incubated for long enough in the bladder First morning samples are most sensitive

21. …but keep in mind: Consequence of missing a UTI is significant in both the short and long term –Urosepsis –Missed urinary tract abnormality –Renal scarring leading to HTN, ESRD »Santen, Altieri. Pediatric Urinary Tract Infection. Emerg Med Clin N A. 2001: 19(3)

22. Potential Guidelines for sending cultures with negative Dip/Microscopy Send culture anyway for all febrile infants under 2 years of age Children with history of previous UTI Children on antibiotic therapy In children whom empiric therapy is started

23. Clinical pearl Girls less than 2 years and boys less than 6 months with fever and a probable source of fever (otitis media, URI) have a significant rate of UTI being about 5%

24. Case 3 3 month old F with fever Initial Test Results Dip »No Leukocyte Esterase »No Nitrites Microscopy »5-10 leuks »No erythrocytes Now what do we do? Treat as UTI? What if she was 4 years old with dysuria? 4 years old and no dysuria?

25. Pyuria on Microscopy >5 WBC/HPF Sensitivity: 54-85% Specificity: 70-81% Microscopic notation of bacteria Sensitivity: 60-90% Specificity: 80-90% Results depend on Volume of urine, observer error, force and duration of centrifugation

26. Urine Dip vs Microscopy Meta-analysis published in Pediatrics in 1999 by Gorelick and Shaw –Conclusions: Dipstick and gram stain perform similarly in detecting UTI in peds with high sensitivity and low FPR These tests have better sensitivity and specificity than the presence of pyuria in either centrifuged or uncentrifuged specimen TPRs and FPRs of the presence of >5 WBC/hpf in a centrifuged urine specimen is sufficiently poor that it cannot be recommended for making a presumptive diagnosis of UTI

27. Urine Dip vs Microscopy Meta-analysis in 2001 by Huicho and colleagues found conflicting results They conclude: “pyuria >/= 10 wbc/hpf and bacteriuria are best suited for assessing the risk of UTI in children” They felt that dipstick tests in the diagnosis of UTI’s in children could not be definitively assessed because number of studies addressing this specific point are small

28. To keep in mind… Incidence of UTI in the 2 and under age group is 5% and may cause few recognizable signs or symptoms other than possibly a fever Greater potential for renal damage compared with older children Meta-analysis by Huicho suggests that “enhanced urinalysis” with gram stain or hemocytometer cell count being positive is the most sensitive method for screening for UTI

29. Case 3 You are reviewing labs from a previous shift and find a positive urine culture in a 3 year old girl who had a normal urinalysis and microscopy You call the parents and she is intermittently febrile with a cough (a cold has been running through the family) Do you prescribe an antibiotic?

30. Case 4 3 y/o M with Fever Urine Dip and Microscopy are negative Are cultures necessary to rule out UTI?

31. Urine Cultures Gold standard for diagnosing UTIs Can get a false negative with betadine mixed in the sample or if child is on antibiotics Cultures can be positive with negative urinalysis »Thought to occur when sample is taken in early infection prior to local inflammatory response is present »May also mean contamination Debate whether children without pyuria but positive cultures should be treated

32. Urine Cultures Asymptomatic bacteriuria Wettergren et al followed 37 infants with culture proven bacteriuria over a 6 year period All went untreated One developed pyelonephritis and no evidence of decreased renal function at the end of the study Reasonable option: –If Child is asymptomatic then reasonable to repeat urinalysis and culture if no antibiotics started –Treat if symptomatic

33. AAP Guidelines Practice guidelines focus specifically on the diagnosis of febrile infants and children <2 years of age Exclude children older than 2 years of age with first presentation of UTI from their review because: –Less risk of renal scarring in this age group –More likely to have symptoms referable to the GU tract

34. Summary of Sens and Spec of urine dip and microscopy TestSensitivitySpecificity LE 8384 Nitrite 5098 LE or Nitrite 8893 LE and Nitrite 7296 Microscopy: WBCs 7381 Microscopy: Bacteria 8183 Enhances UA (cell count or gram stain) 9589

35. References Zorc et al Diagnosis and Management of Pediatric Urinary Tract Infections. Clinical Microbiology Reviews. 2005;18(2):417-22. Huicho et al Metaanalysis of urine screening for determining the risk of urinary tract infection in children. Pediatric Infectious Disease Journal. 2002; 21(1):1-11. Gorelick & Shaw Screening tests for urinary tract infection in children: a meta-analysis. Pediatrics. 1999; 104(5) Herr et al Enhanced urinalysis improves identification of febrile infants ages 60 days and younger at low risk for serious bacterial illness. Pediatrics. 2001; 108(4): 866-871. AAP. Practice Parameter: The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. 1999. www.aap.orgwww.aap.org Chen et al Utility of bedside bladder ultrasound before urethral catheterization in young children. Pediatrics. 2005; 115(1): 108-111. McGillivray et al A head-to-head comparison: clean-void bag versus catheter urinalysis in the diagnosis of urinary tract infection in young children. Journal of Pediatrics. 2005. pp451-456. Liao et al Pediatric Urine Testing. Pediatric Clinics of NA. 2001; 18(6). Santen and Altieri. Pediatric Urinary tract infection. Emergency Medicine Clinics of NA. 2001; 19(3). Jenner and Atzainia. Clean catch or bag specimen in UTI in non toilet trained children. Emergency Medicine Journal. 2006; 2:219-220. Chang & Shortliffe. Pediatric Urinary Tract Infections. Pediatric Clinics of NA. 2006; 53:379-400. Whiting. Rapid tests and urine sampling techniques for the diagnosis of UTI in children under fie years: a systematic review. BMC Pediatrics. 2005; 5(4).