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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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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
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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
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.
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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
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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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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
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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

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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

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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: 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
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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.
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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
# 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
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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.
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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?
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Asymptomatic women in medical
OPD
Asymptomatic women with
diabetes
Asymptomatic women with
cystocele
Pts with diagnosis of pyelonephritis
0 10
0-1
10
1-2
10
2-3
10
3-4
10
4-5
10
5-6
>10
6
Kass E. Asymptomatic infections of the urinary tract. Trans Assoc Am Phys. 1956;69:56–64
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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: 7–14 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: 12–16%
• 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):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–e1494
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):1064–1071
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):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):1748–1759
6. 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

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Action Statement 6
Reflux
Grade
N
Prophylaxis
No
Prophylaxis
P
# of Recurrences / Total N # 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
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Recurrence Rate of Febrile UTI
By Reflux Grade, 1,091 Infants 2–24 Months
0
50
100
150
200
250
None Grade I Grade II Grade III Grade IV
Prophylaxis
No Prophylaxis
Grade of Vesico-Ureteral Reflux (VUR)
NS
NS
NS
NS
NS
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Recurrence Rate of Febrile UTI
By Reflux Grade, 1,091 Infants 2–24 Months
0%
20%
40%
60%
80%
100%
None Grade I Grade II Grade III Grade IV
Prophylaxis
No Prophylaxis
Grade of VUR
(N=373) (N=100) (N=257) (N=285) (N=104)
Recurrence
NS
NS NS
NS
NS
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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)
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%)
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Action Statement 6
Risk of Renal Scarring by Number of UTIs
0%
20%
40%
60%
80%
100%
1 2 3 4 5
Adapted from Jodul U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am. 1987;1(4):713–729
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• 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
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• 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
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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: 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
TM
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