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TM AAP Guideline for the Diagnosis and Management of UTIs in Febrile Infants Unanswered Questions and Unquestioned Answers Kenneth B. Roberts, MD, FAAP.

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Presentation on theme: "TM AAP Guideline for the Diagnosis and Management of UTIs in Febrile Infants Unanswered Questions and Unquestioned Answers Kenneth B. Roberts, MD, FAAP."— Presentation transcript:

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2 TM 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 TM Prepared for your next patient.

3 TM Disclaimers  Statements and opinions expressed are those of the authors and not necessarily those of the American Academy of Pediatrics.  Mead Johnson sponsors programs such as this to give healthcare professionals access to scientific and educational information provided by experts. The presenter has complete and independent control over the planning and content of the presentation, and is not receiving any compensation from Mead Johnson for this presentation. The presenter’s comments and opinions are not necessarily those of Mead Johnson. In the event that the presentation contains statements about uses of drugs that are not within the drugs' approved indications, Mead Johnson does not promote the use of any drug for indications outside the FDA-approved product label.

4 TM 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 AAP 2011 Clinical Practice Guideline

5 TM 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)

6 TM 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.

7 TM 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

8 TM 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

9 TM Driving Force from the 1960s

10 TM Used with permission, ScienceCartoonsPlus.com

11 TM What’s New in This Revision 1.Diagnosis –Abnormal urinalysis as well as positive culture –Positive culture = ≥50,000 colony-forming units (cfu)/mL –Assessment of likelihood of UTI 2.Treatment: Oral as effective as parenteral 3.Imaging: Voiding cystourethrography (VCUG) not recommended routinely after first febrile UTI 4.Follow-up: Emphasis on urine testing with subsequent febrile illnesses

12 TM 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

13 TM 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

14 TM Content Action Statements: 7 – Diagnosis: 3 – Treatment: 1 – Imaging: 2 – Follow-up: 1 Areas for Research: 8

15 TM 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

16 TM 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

17 TM 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 o 88% false-positive overall o 95% in boys o 99% in circumcised boys – Positive culture requires confirmation, which is not possible once antibiotic is started.

18 TM 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.)

19 TM 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.

20 TM 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

21 TM 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 NoYes ≤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.

22 TM 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

23 TM Where Did 100,000 Come From? >10 6 Kass E. Asymptomatic infections of the urinary tract. Trans Assoc Am Phys. 1956;69:56–64

24 TM Urinalysis Positive urinalysis required for diagnosis – 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

25 TM 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

26 TM 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 Evidence quality: A Strong recommendation

27 TM 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 Evidence quality: A Strong recommendation Duration of treatment: 7–14 days Evidence quality: B Recommendation

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

29 TM Action Statement 5 Febrile infants with UTIs should undergo RBUS. 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?

30 TM 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.

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

32 TM

33 Action Statement 6 1.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 2.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–e 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– 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 5.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– 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

34 TM Action Statement 6 Reflux Grade N Prophylaxis No Prophylaxis P # of Recurrences / Total N None3737 / / Grade I722 / 372 / Grade II25711 / / Grade III28531 / / Grade IV10416 / 5521 / ,091

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

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

37 TM 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 Recommendation

38 TM Action Statement 6 After First UTI (N=100) After Recurrence (N=10) No VUR65 (65%)2.6 (26%) Grade I–III VUR29 (29%)5.6 (56%) Grade IV VUR5 (5%)1.2 (12%) Grade V VUR1 (1%)0.6 (6%)

39 TM 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

40 TM N=103 “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 Impact of a More Restrictive Approach to Urinary Tract Imaging After Febrile Urinary Tract Infection

41 TM N=1,576 “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. 2011;128(5):840–847 Childhood Urinary Tract Infections as a Cause of Chronic Kidney Disease

42 TM 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

43 TM Areas for Research (8) 1.Relationship between UTIs and reduced renal function / hypertension 2.Alternatives to invasive collection of urine and culture 3.Role of VUR (and, thus, VCUG) 4.Role of prophylaxis (Randomized Intervention for Children with Vesicoureteral Reflux [RIVUR] study) 5.Genetics 6.Hispanics 7.Further treatment: What and for whom? 8.Duration of treatment

44 TM Summary: What’s New... 1.Diagnosis –Abnormal urinalysis, as well as positive culture –Positive culture = ≥50,000 cfu/mL –Assessment of likelihood of UTI 2.Treatment: Oral as effective as parenteral 3.Imaging: VCUG not recommended routinely after first febrile UTI 4.Follow-up: Emphasis on urine testing with subsequent febrile illnesses

45 TM For more information…  On this topic and a host of other topics, visit Pediatric Care Online is a convenient electronic resource for immediate expert help with virtually every pediatric clinical information need. Must- have resources are included in a comprehensive reference library and time-saving clinical tools.www.pediatriccareonline.org Haven't activated your Pediatric Care Online trial subscription yet? It's quick and easy: simply follow the steps on the back of the card you received from your Mead Johnson representative. Haven't received your free trial card? Contact your Mead Johnson representative or call 888/ today.


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