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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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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
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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
A. Well-designed RCTs or diagnostic
studies on relevant population
Preponderance of
Benefit or Harm
Balance of
Benefit and Harm
Strong
Recommendation
B. RCTs or diagnostic studies with
minor limitations; overwhelmingly
consistent evidence from
observational studies
C. Observational studies (case-control
and cohort design)
D. Expert opinion, case reports,
reasoning from first principles
Abbreviation: RCTs, randomized controlled trials.
Option
Recommendation
Option
No
Recommendation
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Evidence Quality
X. Exceptional situations
where validating studies
cannot be performed and
there is a clear
preponderance of benefit
or harm
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
•
•
•
•
•
Race: White
Age: <12 months
Temperature: ≥39⁰C
Fever: ≥2 days
Absence of another
source of infection
Probability of
UTI
# of Factors
Present
≤1%
No more
than 1
≤2%
No more
than 2
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Probability of UTI: Infant BOYS
Individual Factors
•
•
•
•
Race: Nonblack
Temperature: ≥39⁰C
Fever: >24 hours
Absence of another
source of infection
# of Factors Present
Probability
of UTI
≤1%
≤2%
Circumcised
No
Yes
*
No more
than 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%
Asymptomatic women in medical
OPD
Asymptomatic women with
diabetes
Asymptomatic women with
cystocele
Pts with diagnosis of pyelonephritis
80%
70%
60%
50%
40%
30%
20%
10%
0%
0
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;69:56–64
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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
# of Recurrences / Total N
# of Recurrences / Total N
P
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
250
Prophylaxis
NS
No Prophylaxis
200
NS
150
NS
100
NS
NS
50
0
None
Grade I
Grade II
Grade III
Grade of Vesico-Ureteral Reflux (VUR)
Grade IV
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Recurrence Rate of Febrile UTI
By Reflux Grade, 1,091 Infants 2–24 Months
Recurrence
100%
80%
Prophylaxis
60%
No Prophylaxis
NS
40%
20%
NS
NS
NS
NS
None
(N=373)
Grade I
(N=100)
Grade II
(N=257)
0%
Grade of VUR
Grade III
(N=285)
Grade IV
(N=104)
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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%)
After Recurrence
(N=10)
2.6 (26%)
Grade I–III VUR
29 (29%)
5.6 (56%)
Grade IV VUR
Grade V VUR
5 (5%)
1 (1%)
1.2 (12%)
0.6 (6%)
No VUR
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Action Statement 6
100%
80%
60%
40%
20%
0%
1
2
3
4
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
5
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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):1027–1032
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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, Ikäheimo R, Tapiainen T, et al. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics.
2011;128(5):840–847
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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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