1. Unanswered Questions and Unquestioned AnswersTM
Prepared for your next patient.
AAP Guideline for the Diagnosis and Management of UTIs in Febrile Infants
Unanswered Questions and Unquestioned Answers
Kenneth B. Roberts, MD, FAAP
Professor of Pediatrics (Emeritus)
University of North Carolina
Welcome slide for use during audience walk-in.

2. Disclaimers
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Session agenda

3. AAP 2011 Clinical Practice Guideline
Diagnosis and Management of the Initial UTI in Febrile Infants and Children, 2 to 24 Months*
*Guideline: Pediatrics. 2011;128(3):595–610
Technical report: Pediatrics. 2011;128(3):e749–e770

4. Revision of 1999 Guideline
Routine for American Academy of Pediatrics (AAP) to revise guidelines
New evidence since 1999
New explicit reporting format
“Recommendations” now “Action Statements”
Aggregate evidence quality
Benefits
Harms/risks/costs
Benefit-harms assessment
Value judgments
Role of patient preferences
Exclusions
Intentional vagueness
Policy level (strength of recommendation)

5. Preponderance of Benefit or Harm Balance of Benefit and Harm
Evidence Quality
Preponderance of Benefit or Harm
Balance of Benefit and Harm
A. Well-designed RCTs or diagnostic studies on relevant population
Strong Recommendation
B. RCTs or diagnostic studies with minor limitations; overwhelmingly consistent evidence from observational studies
C. Observational studies (case-control and cohort design)
Recommendation
D. Expert opinion, case reports, reasoning from first principles
Option
No Recommendation
Option
Abbreviation: RCTs, randomized controlled trials.

6. Preponderance of Benefit or Harm
Evidence Quality
Preponderance of Benefit or Harm
X. Exceptional situations where validating studies cannot be performed and there is a clear preponderance of benefit or harm
Strong Recommendation
Recommendation

7. AAP Subcommittee on Urinary Tract Infection (UTI)
Stephen M. Downs, MD, MS: Epidemiology/informatics
S. Maria E. Finnell, MD, MS: Epidemiology/informatics
Stanley Hellerstein, MD: Pediatric nephrology
Kenneth B. Roberts, MD, Chair: General pediatrics
Linda D. Shortliffe, MD: Pediatric urology
Ellen R. Wald, MD: Pediatric infectious diseases
J. Michael Zerin, MD: Pediatric radiology
Caryn Davidson, MA: AAP staff

8. Driving Force from the 1960s

9. Used with permission, ScienceCartoonsPlus.com

10. What’s New in This Revision
Diagnosis
Abnormal urinalysis as well as positive culture
Positive culture = ≥50,000 colony-forming units (cfu)/mL
Assessment of likelihood of UTI
Treatment: Oral as effective as parenteral
Imaging: Voiding cystourethrography (VCUG) not recommended routinely after first febrile UTI
Follow-up: Emphasis on urine testing with subsequent febrile illnesses

11. Population Addressed
Infants and young children, 2–24 months of age, with unexplained fever
Rate of UTI: ~5%
Rate of scarring: Higher than in older children

12. Population Addressed
Infants and young children, 2–24 months of age, with unexplained fever
Rate of UTI: ~5%
Rate of scarring: Higher than in older children
Excludes: <2 months of age
Excludes: >24 months of age

13. Content Action Statements: 7 Diagnosis: 3 Treatment: 1 Imaging: 2
Follow-up: 1
Areas for Research: 8

14. Action Statement 1
If a clinician decides that a febrile infant with no apparent source for the fever requires antimicrobial therapy because of ill appearance or another pressing reason, a urine specimen should be obtained by catheterization for both culture and urinalysis before an antimicrobial is given.
Evidence quality: A
Strong recommendation

15. Methods of Collecting Specimen
Suprapubic aspiration: “Gold standard,” but
Variable success rates: 23–90% (higher with ultrasound guidance)
Requires technical expertise and experience
Often viewed as invasive
More painful than catheterization
May be no alternative in boys with severe phimosis or girls with tight labial adhesions

16. Methods of Collecting Specimen
Bag urine
Can’t avoid getting “vaginal wash” in girl or contamination in uncircumcised boy.
Not suitable for culture.
Negative culture rules out UTI, but
Positive culture likely to be false-positive
88% false-positive overall
95% in boys
99% in circumcised boys
Positive culture requires confirmation, which is not possible once antibiotic is started.

17. Methods of Collecting Specimen
Catheterization
Compared to suprapubic aspiration:
Sensitivity = 95%
Specificity = 99%
Requires some skill, particularly in small infant girls. (Tip: If unsuccessful, leave catheter in.)

18. Action Statement 2
If a febrile infant is assessed as not requiring immediate antimicrobial therapy, then the likelihood of UTI should be assessed.
If likelihood is low (<1%, <2%), it is reasonable to follow the child clinically.
If the likelihood is not low, there are two options:
Obtain specimen by catheter for culture and urinary analysis (UA).
Obtain specimen by any means for UA and only culture those with positive UA.

19. Probability of UTI: Infant GIRLS
Individual Factors
Probability of UTI
# of Factors Present
Race: White
Age: <12 months
Temperature: ≥39⁰C
Fever: ≥2 days
Absence of another source of infection
≤1%
No more than 1
≤2%
No more than 2

20. Probability of UTI: Infant BOYS
Individual Factors
Probability of UTI
# of Factors Present
Race: Nonblack
Temperature: ≥39⁰C
Fever: >24 hours
Absence of another source of infection
Circumcised No
Yes
≤1% *
No more than 2
≤2%
None
No more than 3
*Probability of UTI exceeds 1% even with no risk factors other than being uncircumcised.

21. Action Statement 3 Diagnosis of UTI requires both: Positive culture
≥50,000 cfu/mL of uropathogen cultured from catheter specimen, AND
Positive urinalysis
Evidence quality: C
Recommendation

22. Where Did 100,000 Come From?
>106
Kass E. Asymptomatic infections of the urinary tract. Trans Assoc Am Phys. 1956;69:56–64

23. Urinalysis Positive urinalysis required for diagnosis Positive
Positive culture with “negative” urinalysis
Contamination
Asymptomatic bacteriuria
Urinalysis not sensitive enough
Positive
Dipstick: +LE (leukocyte esterase) and/or +nitrite
Microscopy: White blood cells ± bacteria

24. Action Statement 4
Choice of route: Initiating treatment orally or parenterally is equally efficacious, so choice is based on practical considerations.
Evidence quality: A
Strong recommendation

25. Action Statement 4
Choice of route: Initiating treatment orally or parenterally is equally efficacious, so choice is based on practical considerations.
Evidence quality: A
Strong recommendation
Choice of drug: Based on local sensitivity patterns, adjusted according to sensitivity of particular uropathogen

26. Action Statement 4
Choice of route: Initiating treatment orally or parenterally is equally efficacious, so choice is based on practical considerations.
Evidence quality: A
Strong recommendation
Choice of drug: Based on local sensitivity patterns, adjusted according to sensitivity of particular uropathogen
Duration of treatment: 7–14 days
Evidence quality: B
Recommendation

27. Action Statement 5
Febrile infants with UTIs should undergo renal and bladder ultrasonography (RBUS),
Evidence quality: C
Recommendation

28. Action Statement 5 Febrile infants with UTIs should undergo RBUS. Why:
Evidence quality: C
Recommendation
Why:
Yield of abnormal findings: 12–16%
Permanent renal damage (1 year later)
Sensitivity: 41%
Specificity: 81%
Actionable findings sufficient to warrant?

29. Action Statement 5 Febrile infants with UTIs should undergo RBUS.
Evidence quality: C
Recommendation
When:
Decide clinically: Within 48 hours if not responding to treatment as expected, unusually ill, or extenuating circumstances; otherwise, when convenient.

30. Action Statement 6
VCUG is not recommended to be performed routinely after the first febrile UTI if RBUS is normal.
Evidence quality: B
Recommendation

31. Vesico-Ureteral Reflux
Law &
Order
Vesico-Ureteral Reflux

32. Action Statement 6
Garin EH, Olavarrio F, Garcia Nieto V, et al. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized controlled study. Pediatrics. 2006;117(3):626–632
Pennesi M, Travan L, Peratoner L, et al. Is antibiotic prophylaxis in childrfen with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized controlled trial. Pediatrics. 2008;121(6):e1489–e1494
Montini G, Rigon L, Zuccheta P, et al. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Pediatrics. 2008;122(5):1064–1071
Roussey-Kesler G, Gadjos V, Idres N, et al. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux results from a prospective randomized study. J Urol. 2008;179(2):674–679
Craig JC, Simpson JM, Williams GJ, et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med. 2009;361(18):1748–1759
Brandström P, Esbjörner E, Herthelius M, et al. The Swedish reflux trial in children: III. Urinary tract infection pattern. J Urol. 2010;184(1):286–291

33. Action Statement 6 Reflux Grade N Prophylaxis No Prophylaxis P None
# of Recurrences / Total N
None
373
7 / 210
11 / 163
0.15
Grade I 72
2 / 37
2 / 35
1.00
Grade II
257
11 / 133
10 / 124
0.95
Grade III
285
31 / 140
40 / 145
0.29
Grade IV
104
16 / 55
21 / 49
0.14
1,091

34. Grade of Vesico-Ureteral Reflux (VUR)
Recurrence Rate of Febrile UTI By Reflux Grade, 1,091 Infants 2–24 Months NS NS NS NS NS
Grade of Vesico-Ureteral Reflux (VUR)

35. Recurrence Rate of Febrile UTI By Reflux Grade, 1,091 Infants 2–24 MonthsNS NS NS NS NS
(N=373) (N=100) (N=257) (N=285) (N=104)
Grade of VUR

36. Action Statement 6
If RBUS is abnormal, VCUG may be part of additional imaging required to evaluate the abnormality.
Evidence quality: B
Recommendation
Further evaluation should be conducted if there is a recurrence of febrile UTI.
Evidence quality: X

37. Action Statement 6 Grade IV VUR 5 (5%) 1.2 (12%) Grade V VUR 1 (1%)
After First UTI
(N=100)
After Recurrence
(N=10)
No VUR
65 (65%)
2.6 (26%)
Grade I–III VUR
29 (29%)
5.6 (56%)
Grade IV VUR
5 (5%)
1.2 (12%)
Grade V VUR
1 (1%)
0.6 (6%)

38. Risk of Renal Scarring by Number of UTIs
Action Statement 6
Risk of Renal Scarring by Number of UTIs
Adapted from Jodul U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am. 1987;1(4):713–729

39. Impact of a More Restrictive Approach to Urinary Tract Imaging After Febrile Urinary Tract Infection
“By restricting urinary tract imaging after an initial febrile UTI [based on NICE guidelines, 2007], rates of voiding cystourethrography and prophylactic antibiotic use decreased substantially without increasing the risk of UTI recurrence within 6 months and without an apparent decrease in detection of high-grade VUR.”
Schroeder AR, Abidari JM, Kirpekar R, et al. Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. Arch Pediatr Adolesc Med. 2011;165(11):1027–1032

40. Childhood Urinary Tract Infections as a Cause of Chronic Kidney Disease
“VUR with UTI without structural abnormalities in the kidneys seems not to cause CKD.”
“Active treatment of VUR seems not to reduce the occurrence of CKD and, in large prospective follow-up studies, the renal function of patients with VUR has been well preserved.”
Salo J, Ikäheimo R, Tapiainen T, et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics ;128(5):840–847

41. Action Statement 7
Following confirmation of UTI, parents or guardians should be instructed to seek prompt medical evaluation for future febrile illnesses to ensure that recurrent infections can be detected and treated promptly.
Evidence quality: C
Recommendation

42. Areas for Research (8)
Relationship between UTIs and reduced renal function / hypertension
Alternatives to invasive collection of urine and culture
Role of VUR (and, thus, VCUG)
Role of prophylaxis (Randomized Intervention for Children with Vesicoureteral Reflux [RIVUR] study)
Genetics
Hispanics
Further treatment: What and for whom?
Duration of treatment

43. Summary: What’s New . . . Diagnosis
Abnormal urinalysis, as well as positive culture
Positive culture = ≥50,000 cfu/mL
Assessment of likelihood of UTI
Treatment: Oral as effective as parenteral
Imaging: VCUG not recommended routinely after first febrile UTI
Follow-up: Emphasis on urine testing with subsequent febrile illnesses

44. For more information…
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