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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

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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 presenters 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.

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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):595610 Technical report: Pediatrics. 2011;128(3):e749e770

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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)

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Evidence Quality

Preponderance of Benefit or Harm Strong Recommendation

Balance of Benefit and Harm

A. Well-designed RCTs or diagnostic

studies on relevant population

B. RCTs or diagnostic studies with

minor limitations; overwhelmingly consistent evidence from observational studies Option

C. Observational studies (case-control

and cohort design)

Recommendation
Option No Recommendation

D. Expert opinion, case reports,

reasoning from first principles
Abbreviation: RCTs, randomized controlled trials.

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Evidence Quality

Preponderance of Benefit or Harm

Strong Recommendation

X. Exceptional situations
where validating studies cannot be performed and there is a clear preponderance of benefit or harm

Recommendation

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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

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Driving Force from the 1960s

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Used with permission, ScienceCartoonsPlus.com

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Whats 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

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Population Addressed
Infants and young children, 224 months of age, with unexplained fever
Rate of UTI: ~5% Rate of scarring: Higher than in older children

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Population Addressed
Infants and young children, 224 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

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

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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

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Methods of Collecting Specimen

Suprapubic aspiration: Gold standard, but
Variable success rates: 2390% (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

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Methods of Collecting Specimen

Bag urine
Cant 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.

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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.)

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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.

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Probability of UTI: Infant GIRLS

Individual Factors Probability of UTI 1% # of Factors Present

Race: White Age: <12 months Temperature: 39C Fever: 2 days Absence of another source of infection

No more than 1
No more than 2

2%

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Probability of UTI: Infant BOYS

Individual Factors Race: Nonblack Temperature: 39C Fever: >24 hours Absence of another source of infection # of Factors Present Probability of UTI 1% Circumcised No Yes * No more than 2

2%

None

No more than 3

*Probability of UTI exceeds 1% even with no risk factors other than being uncircumcised.

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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

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Where Did 100,000 Come From?

90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
Asymptomatic women in medical OPD Asymptomatic women with diabetes Asymptomatic women with cystocele Pts with diagnosis of pyelonephritis

100-1 101-2 102-3 103-4 104-5 105-6 >106

Kass E. Asymptomatic infections of the urinary tract. Trans Assoc Am Phys. 1956;69:5664

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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

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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

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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

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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: 714 days

Evidence quality: B Recommendation

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Action Statement 5
Febrile infants with UTIs should undergo renal and bladder ultrasonography (RBUS),

Evidence quality: C Recommendation

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Action Statement 5
Febrile infants with UTIs should undergo RBUS.

Evidence quality: C Recommendation

Why:

Yield of abnormal findings: 1216% Permanent renal damage (1 year later)

Sensitivity: 41% Specificity: 81%

Actionable findings sufficient to warrant?

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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.

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Action Statement 6
VCUG is not recommended to be performed routinely after the first febrile UTI if RBUS is normal.

Evidence quality: B Recommendation

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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):626632 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):e1489e1494 3. 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):10641071 4. 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):674679 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):17481759 6. Brandstrm P, Esbjrner E, Herthelius M, et al. The Swedish reflux trial in children: III. Urinary tract infection pattern. J Urol. 2010;184(1):286291

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Action Statement 6
Reflux Grade N Prophylaxis
# of Recurrences / Total N

No Prophylaxis
# of Recurrences / Total N

None
Grade I Grade II Grade III Grade IV

373
72 257 285 104 1,091

7 / 210
2 / 37 11 / 133 31 / 140 16 / 55

11 / 163
2 / 35 10 / 124 40 / 145 21 / 49

0.15
1.00 0.95 0.29 0.14

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Recurrence Rate of Febrile UTI

By Reflux Grade, 1,091 Infants 224 Months
250 Prophylaxis

NS
200 150 100 50 0 None Grade I

No Prophylaxis

NS

NS

NS

NS

Grade II

Grade III

Grade IV

Grade of Vesico-Ureteral Reflux (VUR)

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Recurrence Rate of Febrile UTI

By Reflux Grade, 1,091 Infants 224 Months Recurrence
100% 80% Prophylaxis 60% 40% 20% 0% None (N=373) Grade I (N=100) Grade II (N=257) Grade III (N=285) Grade IV (N=104) No Prophylaxis

NS NS NS NS NS

Grade of VUR

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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

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Action Statement 6
After First UTI (N=100) 65 (65%)
29 (29%)

No VUR Grade IIII VUR

After Recurrence (N=10) 2.6 (26%)

5.6 (56%)

Grade IV VUR Grade V VUR

5 (5%) 1 (1%)

1.2 (12%) 0.6 (6%)

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Action Statement 6
100% 80% 60% 40% 20% 0% 1 2 3 4 5

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):713729

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Impact of a More Restrictive Approach to Urinary Tract Imaging After Febrile Urinary Tract Infection
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):10271032

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Childhood Urinary Tract Infections as a Cause of Chronic Kidney Disease 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 followup studies, the renal function of patients with VUR has been well preserved.
Salo J, Ikheimo R, Tapiainen T, et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics. 2011;128(5):840847

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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

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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

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Summary: Whats 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

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