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MINERVA PEDIATR 2012;64:145-57

Urinary tract infections in children: a review

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D. BUONSENSO, L. CATALDI

Febrile urinary tract infection is the most


common serious bacterial infection in childhood, but the most appropriate evaluation of
children with this condition is still unclear,
overall regarding the best long-term management of children after a first UTI. Here we review current recommendations for the diagnosis, treatment, imaging evaluation and use
of antibiotic prophylaxis inchildrenwith the
firstfebrile urinary tract infection. Nevertheless, the development of a universally accepted diagnostic protocol remains elusive.
Key words:  Urinary tract infections - Child Ultrasonography.

cute pyelonephritis is the most common serious bacterial infection in childhood. About 7 to 8% of girls and 2% of boys
have a urinary tract infection (UTI) during
the first 8 years of life.1, 2 Febrile UTIs have
the highest incidence during the first year of
life in both sexes, whereas nonfebrile UTIs
occur predominantly in girls older than 3
years.2
Establishing the diagnosis is difficult in
early childhood due to the absence of specific symptoms, and difficulty in collection
of not contaminated urine samples without
invasive methods (urethral catheterization
or suprapubic aspiration [SPA]).
After infancy, UTIs confined to the blad-

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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.

Corresponding author: D. Buonsenso, Department of


Pediatrics Catholic University of the Sacred Heart, L.go A.
Gemelli 8, 00168 Rome, Italy.
E-mail: danilobuonsenso@gmail.com

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Sacro Cuore Catholic University, Rome, Italy

der are generally accompanied by localized


symptoms and are easily treated. In contrast,
the presence of fever increases the probability of kidney involvement (53-84% sensitivity, 44-92% specificity) 3 and is associated
with an increased likelihood of underlying
nephrourologic abnormalities and a greater
risk of consequent renal scarring,4 supporting the concept that delays in the institution
of antibiotic treatment of pyelonephritis increase the risk of renal damage.5, 6
Since recently, kidney scarring related to
UTI has been considered a cause of substantial long-term morbidity.7 Thus, children
with proven infections have been intensively evaluated and treated, and they have
often undergone surgery or have received
long-term antibiotic prophylaxis.3, 7-12 These
approaches,13, 14 especially voiding cystourethrography (VCUG) 15-22 and the use
of antibiotic prophylaxis 23-26 have been recently questioned.
One of these studies showed a high prevalence of scarring (38%) before treatment
was started, whereas rates of new scarring
and progression of existing scarring were
low (2% and 9%, respectively) and were
unrelated to persistent reflux or breakthrough infections.11 Such results highlight
an important issue: the distinction between

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ride) of the bacteria binds to CD14 on the


cell surface, activating toll-like receptor 4.
Through a different complex and not yet
completely understood steps, this activates
transcription factor nuclear factor B (NFB), which migrates into the cell nucleus,
stimulating production of inflammatory factors, including cytokines, chemokines, nitric oxide, and transforming growth factor
. These mediators induce an inflammatory
response, which increases vascular permeability, recruitment of neutrophils and release of mediators that on one hand help
to resolve the infection (with the help of
antimicrobial agents), on the other hand are
also responsible in part for the ensuing kidney scarring.27

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primary renal damage that precedes infection and scars related to UTI. Primary renal
damage is linked to prior obstruction, genetic and developmental factors that result
in maldevelopment (hypodysplasia) of the
urinary tract, or both. However, inflammatory processes (pyelonephritis) that occur
in the context of infection may also produce scars.27
In 2007, the United Kingdoms National
Institute for Health and Clinical Excellence
(NICE) 28 published new guidelines for the
management of UTI in children, which recommend more selective
use of renal ultrasonography (US) and
VCUG. Similarly, the 2011 American Academy of Pediatrics guidelines 29 do not recommend routine use of imaging techniques.
This new attitude could be of particular
interest, since current imaging, prophylaxis,
and prolonged follow-up strategies place
a heavy burden on patients, families, and
national health systems resources and carry
risks without evidence of benefit.
Methods

This review focuses on pathophysiology,


diagnosis and management of initial UTIs
in febrile infants and young children who
have no obvious neurologic or anatomic
abnormalities known to be associated with
recurrent UTI or renal damage. Following
results cannot be generalized to newborns
and infants less than 2 months of age, since
there are special considerations in this age
group to be considered and that limit the
applicability of evidences derived from
studies of older children.

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or other proprietary information of the Publisher.

BUONSENSO

Pathophysiology of febrile UTI


Acute pyelonephritis occurs when bacteria ascend to the kidneys and cause intrarenal infection. Escherichia coli bacteria are
characterized by the presence of P fimbriae which permit them to attach to uroepithelial cells and to not be flushed out by
urine flow. The endotoxin (lipopolysaccha-

146

When to suspect a UTI?

NICE guidelines 29 highlight the need of


considering a diagnosis of UTI in all infants and children with unexplained fever
of 38 C or higher after 24 hours at the latest, and in children having symptoms and
signs suggestive of UTI, including fever and
non-specific symptoms, such as lethargy, irritability, malaise, failure to thrive, vomiting,
poor feeding, abdominal pain, jaundice (or
having more specific symptoms particularly
in older children - such as frequency, dysuria, loin tenderness, dysfunctional voiding,
changes to continence, hematuria, and offensive or cloudy urine).28
Similarly, the AAP 2011 guidelines 29 state
that a clinician should consider a UTI whenever he thinks that a febrile infant with no
apparent source of infection requires antibiotic therapy because of ill appearance.
Moreover, the AAP 2011 guidelines encourage the doctor to determine the risk that a
particular child has to have a UTI during a
febrile episode (Table I).
How to diagnose a UTI?
The clinician should ensure that a urine
specimen is obtained for both culture and
urinalysis before an antimicrobial agent is

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BUONSENSO

the test. Table II describes characteristics of


urinalysis tests.
To establish the diagnosis of UTI, clinicians should require both urinalysis results
that suggest infection (pyuria and/or bacteriuria) and the presence of at least 50 000
colony-forming units (CFUs) per mL of a
uropathogen cultured from a urine specimen
obtained through catheterization or SPA.
When should a child be hospitalized?

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administered; the specimen needs to be obtained through catheterization (95% sensitivity, 99% specificity) 30-32 or SPA, because
the diagnosis of UTI cannot be established
reliably through culture of urine collected
in a bag (up to 88% of false-positive results,
68% specificity).33-35 The techniques required for catheterization and SPA are well
described.36
Urinalysis cannot substitute for urine
culture to document the presence of UTI
but needs to be used in conjunction with
culture, since urine culture results are not
available for at least 24 hours.
Urinalysis can be performed on any
specimen, including one collected from a
bag applied to the perineum. However, the
specimen must be fresh (<1 hour after voiding with maintenance at room temperature
or <4 hours after voiding with refrigeration), to ensure sensitivity and specificity of

Hospital admission is indicated in the following situations:37


neonates and infants younger than 3
months;
severely ill children (sepsis, dehydration, vomiting);
concern of noncompliance;
fever persisting after 3 days of appro-

Table I.UTI probability among febrile boys and girls.


Probability of UTI

N. of factors present
(girls) (31)

N. of factors present (uncircumcised boys)


(32)

N. of factors present
(circumcised boys) (32)

1%

2%

No more than 2

Always >1% even with no risk factors


other than being uncircumcised
None

No more than 3

Risk factors for girls: white race; age <12months; temperature 39C; fever lasting more than 2 days; absence of another source
of infection.
Risk factors for boys: nonblack race; temperature 39C; fever lasting more than 24 hours; absence of another source of
infection.
Adapted from AAP guidelines 2011.29

Table II.Characteristics of urinalysis components.


Test

Nitrite test

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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.

URINARY TRACT INFECTIONS IN CHILDREN

Leukocyte esterase test


Microscopy, WBCs

Comments

little value in ruling out UTI (not all urinary pathogens reduce nitrate to nitrite); helpful when positive
(highly specific)
it distinguishes
individuals with asymptomatic bacteriuria (absence
of leukocyte esterase in the urine) from those with
true UTI.
The absence of pyuria in children with true UTIs
is rare
WBCs may be found in the urine during other conditions (eg, streptococcal infections or Kawasaki
disease), and after vigorous exercise.
The key to distinguishing true UTI from asymptomatic bacteriuria is the presence of pyuria.

Microscopy, bacteria

Sensitivity % (range) Specificity % (range)

53 (1582)

98 (90100)

83 (6794)

78 (6492)

73 (32100)

81 (4598)

81 (1699)

83 (11100)

Adapted from AAP guidelines 2011.29

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priate antibiotic treatment as shown by the


sensitivity testing.
How to treat a UTI?

Children should be treated for 7 to 14


days.27-29
Cephalosporins and amoxicillin/clavulanate are the most used oral antibiotics.
When intravenous treatment is required, no
particular antibiotic has been shown to be
superior; cephalosporins and aminoglycosides are frequently recommended.45, 46
Table III lists the main characteristics of
commonly used antibiotics for febrile UTI.

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The goals of treatment of acute UTI are


to eliminate the acute infection, to prevent
complications, and to reduce the likelihood
of renal damage. The majority of children
can be treated orally.38-40 Patients who appears to be toxic or are unable to retain
oral intake should be treated parentally until they exhibit clinical improvement, usually within 24 to 48 hours, and are able to
retain orally administered fluids and medications.29
Only antimicrobials that reach high blood
concentrations should be used to treat febrile infants with
UTIs, because parenchymal and serum
antimicrobial concentrations may be insufficient to treat pyelonephritis or urosepsis
when using agents that are excreted in the
urine but do not achieve therapeutic concentrations in the bloodstream.27
The antimicrobial agent should be chosen based on local antimicrobial sensitivity
patterns (if available) and the choice should
be re-evaluated according to sensitivity testing of the isolated uropathogen.29 This concept is of primary importance, since antibiotic resistance is a growing concern.41 The
rate of isolated E. coli (the most common
organism isolated,19 accounting for up to
80% of infections) resistant to first-line antibiotics such as ampicillin and trimethoprim/
sulfamethoxazole is constantly increasing.42,
43 Chakupurakal et al.44 have found in the
United Kingdom that E. coli UTIs were
uniformly susceptible to amoxicillin/clavulanate in 2002, but the resistant pattern
changed in 2008, with 48% of E. coli UTIs
being resistant.41
Even though a recent Belgium prospective study 41 involving 209 children treated
for first febrile UTI found an 8% resistance
rate to amoxicillin/clavulanate, the concern
of antibiotic resistance should always be
taken into consideration in daily clinical
practice.

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(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.

BUONSENSO

148

What to do after a first febrile UTI?

Prophylaxis

For the past 4 decades, continuous antimicrobial administration as prophylaxis


aimed to protect the kidneys from further
damage after an initial UTI in children with
genitourinary abnormalities was the mainstay of the management of UTI, since recurrent UTIs were considered to increase renal
damage.29
However, since there is a significant
number of infants in whom vescico-ureteral
reflux (VUR) cannot be demonstrated who
develop pyelonephritis, the effectiveness of
antimicrobial prophylaxis has been challenged in the past decade. Several studies have suggested that prophylaxis does
not confer the desired benefit of preventing recurrent febrile UTI.24-26 A 2 analysis
(2-tailed) and a formal meta-analysis of
these studies did not detect a statistically
significant benefit of prophylaxis in preventing recurrence of febrile UTI/pyelonephritis in infants without reflux or those
with grades I, II, III, or IV VUR.29 Because
only 5 infants with grade V VUR were included in these studies, this statement cannot be used for children with grade V VUR
until randomized controlled trials (RCTs)
will be conducted with this population.29 In
fact, prompt diagnosis and effective treatment of a febrile UTI recurrence (see Table
IV for the definition of recurrence) may be
of greater importance regardless of whether VUR is present or the child is receiving
antimicrobial prophylaxis. Therefore, current AAP guidelines state that antimicrobial

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Table III.Main characteristics of commonly used antibiotics for febrile UTI.


Antimicrobial
agent

Dosage
(parenteral
treatment)

Dosage
(oral treatment)

Pharmacokinetics 47

Pharmacodnamic 47

Comments 27, 47

Amoxicillinclavulanate

2040 mg/kg per d in


3 doses (30)
45 mg per kg twice
per day (dose expressed
in amoxicillin-equivalent units)

Half-life: 1.5h
Metabolism: hepatic
Excretion: urine
Distribution: widely
distributed (except
CNS)

inhibits bacterial cell


Increasing resistance
wall synthesis by
binding to penicillinbinding proteins. Addition of clavulanate
inhibits beta-lactamase
producing bacteria

Trimethoprimsulfamethoxazole

612 mg/kg trimethoprim and 30-60 mg/kg


sulfamethoxazole
per d in 2 doses (30)
4 mg per kg twice per
day (dose expressed
in
trimethoprimequivalent units)

Half-life: TMP 8-10h,


SMX 10-12h
Metabolism: liver
Excretion: urine
Enzymes inhibited:
hepatic CYP2C9

TMP Inhibits dihydrofolate reductase; SMX


competes with paraaminobenzoic acid

75 mg/kg,
every 24 h

Half life: 8 hours


Absorption
IM: well absorbed
Distribution
Widely throughout the
body including gallbladder, lungs, bone,
bile, CSF (higher concentrations achieved
when meninges are
inflamed); crosses placenta; enters amniotic
fluid and breast milk
Metabolism: liver
Excretion: urine (3365% as unchanged
drug), the remainder
secreted in bile and
ultimately in feces as
microbiologically inactive compounds.

Third-generation
cephalosporin with
broad-spectrum,
Gram- activity;
lower efficacy against
Gram+ organisms;
higher efficacy against
resistant organisms.
Bactericidal activity
results from inhibiting
cell wall synthesis
by binding to one or
more penicillin binding proteins. Exerts
antimicrobial effect by
interfering with synthesis of peptidoglycan, a major structural
component of bacterial cell wall. Bacteria
eventually lyse due to
the ongoing activity
of cell wall autolytic
enzymes while cell
wall assembly is arrested.

150 mg/kg
per d,
divided every
68 h

Half-life: 1-1.5h
Penicillin-binding
Distribution
proteins
Widely throughout the
body
Metabolism: partially
in liver to active metabolite desacetylcefotaxime
Excretion: urine

3rd generation cephalosporin

Metabolism: partial,
hepatic
Excretion: urine

Arrest bacterial growth


by binding to one or
more penicillin-binding proteins, which,
in turn, inhibit the
final transpeptidation
step of peptidoglycan
synthesis in bacterial
cell wall synthesis,
thus inhibiting cell
wall biosynthesis

3rd generation cephalosporin


Good coverage for
pseudomonas

Penicillin-binding
proteins

1st generation cephalosporin

Cefotaxime

High resistance rates;


risk of allergic reaction

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Ceftriaxone

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URINARY TRACT INFECTIONS IN CHILDREN

Ceftazidime

100150 mg/kg
per d,
divided every
8h

Cefixime

8 mg/kg per d in 1
dose

Half-life: 0.8-1.3h
Excretion: unchanged
in urine (80-100%)

Cephalexin

50100 mg/kg per d


in 4 doses

Half-life: 0.8-1.3h
Excretion: unchanged
in urine (80-100%)

Advantage of oncedaily dosing; contraindicated


in neonates, especially
premature infants;
increasing resistance
(for all cephalosporins)

1st generation cephalosporin

(Continue)

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Table III.Main characteristics of commonly used antibiotics for febrile UTI.


Antimicrobial
agent

Dosage
(parenteral
treatment)

Dosage
(oral treatment)

Pharmacokinetics 47

(Continues from previous page)

Pharmacodnamic 47

Comments 27, 47

10 mg/kg per d in 2
doses

Half-life: 2-3h (prolonged with renal


impairment)
Absorption: oral 50%,
acid stable
Metabolism: liver, to
active metabolite
Excretion: unchanged
in urine 80%

Binds to one or more 3rd generation cephaof the penicillinlosporin


binding proteins; bacteria eventually lyse
because of ongoing
activity of cell wall autolytic enzymes while
cell wall assembly is
arrested

Cefprozil

30 mg/kg per d in 2
doses

Half-life: 1.3h
Absorption: oral 94%
Metabolism: liver
Excretion: urine 61%
unchanged

Binds to one or more


of the penicillin-binding proteins, which in
turn inhibits cell wall
synthesis and results
in bactericidal activity.

2nd generation cephalosporin


Has Gram+ activity that
1st generation have and
adds activity against P
mirabilis, H influenza,
E coli, K pneumonia
and M catarrhalis

Half-life: 1-2h
Absorption increased
with food
Metabolism: liver
partially
Excretion: urine 66100% unchanged

Binds to penicillin binding proteins


and inhibits final
transpeptidation step
of peptidoglican
synthesis; resists
degradation by betalactamase.

2nd generation cephalosporin

7.5 mg/kg
per d,
divided every
8h

Half-life: 2-3 hours


Excretion: urine as
unchanged drug
Clearence: directly related to renal funtion

Interferes with bacterial protein synthesis


by binding to 30S
and 50S ribosomal
subunits

Tobramycin

5 mg/kg per d,
divided every
8h

Half-life: 2-3 hours


Excretion: urine
within 24h in normal
renal funtion

binds to 30S and 50S


ribosomal subunits

Amikacin

7.5 mg per kg
twice per day

Half-life: 2-3 hours


Eliminated renally.
Administered IV over
30-60 min.
Distribution:
Primiraly into
extracelllular fluid
(highly hydrophilic);
penetrates blood-brain
barrier when meninges inflamed.
Half-life: 1h, metabolites 1-1.5h.
Metabolism: hepatic
Excretion:
Piperacillin 68% urin,
tazobactam 80% urine,
both also in bile

Useful for patients with


cephalosporin allergy;
nephrotoxic; serum
levels must be monitored
and dosage adjusted
accordingly; single
daily
dosage supported by
meta-analysis 55

Irreversibly binds to
30S subunit of bacterial ribosomes; blocks
recegnition step in
protein synthesis;
causes growth inhibition. For Gram- bacterial coverage of
infections resistant
to gentamicin and
tobramycin.
Anti-pseudomonal
Broad spectrum of
penicillin plus betabactericidal activity
lactamase inhibitor.
Inhibits biosynthesis
of cell wass mucopeptide and is effective
during stage of active
multiplication

Half-life: 4-6 h
Excretion: urine (2565%), feces (20-40%)
Enzymes inhibited:
hepatic CYP1A2

Inhibits relaxation of
DNA; inhibits DNAgyrase in susceptible
organisms; promotes
breakage of doublestranded DNA

Cefuroxime
axetil

Gentamicin

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Cefpodoxime

Piperacillin tazobactam

2030 mg/kg per d in


2 doses

29 months of
age: 80 mg of
piperacillin and
10 mg
of tazobactam
per kg three
times per day;
more
than 9 months
of age: 100 mg
of piperacillin
and
12.5 mg of
tazobactam per
kg three times
per day

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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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BUONSENSO

Ciprofloxacin

150

1020 mg per kg
twice per day

MINERVA PEDIATRICA

A second choice for


the treatment of complicated
urinary tract infections;
increasing resistance;
increased risk of musculoskeletal adverse
events

April 2012

BUONSENSO

Table IV.Definition of recurrent UTI.


Consider a UTI as recurrent with any of the following
Two or more episodes of UTI with acute pyelonephritis or upper UTI
One episode of UTI with acute pyelonephritis or upper UTI plus one or more episode of UTI with cystitis or lower
urinary tract infection
Three or more episodes of UTI with cystitis or lower UTI
Adapted from NICE guidelines.28

ics utilised in the literature, but their resistance rate is increasing.


The Randomized Intervention for Children
With Vesicoureteral Reflux study (RIVUR;
ClinicalTrials.gov number, NCT00405704)
which is enrolling 600 children 2 to 72
months of age with grade I to IV vesicoureteral reflux after an index febrile or
symptomatic UTI, will probably provide
valuable information.51

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prophylaxis is not as effective as previously


thought. Similarly, NICE guidelines suggest
to not prescribe antibiotic prophylaxis routinely.28
Nevertheless, a large trial involving 576
children demonstrates a modest favorable
effect on the recurrence of both symptomatic and febrile UTIs.48 A more recent
RCT (203 children) shows favorable effects
on recurrence of infections, especially in
girls >1 year old, with reflux grade III and
IV.49 There was no benefit in boys from
any of the treatments in that study. An
increased bacterial resistance to the prophylactic drug has been described in these
studies.
Montini et al.27 in a recently published review highlight that the role of prophylaxis
is questionable in children with no reflux or
with grade I or II reflux, given a recurrence
rate for infection of 3 to 8% per year without prophylaxis.42 For children with grade
III to V reflux, who have a much higher rate
of reinfection (28% to 37%) 42, 49 prophylaxis would seem appropriate, particularly
in girls.
According to the latest Italian Guidelines
on the management of UTI in children, antibiotic prophylaxis 50 should not be recommended routinely in infants and children
after the first UTI.
It has to be considered in infants and
children:
a. after the treatment of the acute episode until cystography is performed;
b. with reflux grade >III;
c. with recurrent febrile UTIs (>3 febrile
UTIs within 12 months).
The optimal duration of antibiotic prophylaxis is not well established; we suggest 1
to 2 years. Amoxicillin-clavulanate and cotrimoxazole are the most common antibiot-

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Adjunctive treatments

Cranberry juice, which is considered to


inhibit bacterial adhesion to uroepithelial
cells,27 has been used for the prevention
of recurrent UTIs 52 and its effectiveness
in decreasing the number of symptomatic
UTIs in women 53 and children 54 has been
shown.
Circumcision has also been shown to be
associated with a reduced risk of UTI,55 but
it would provide a net clinical benefit only
in boys at high risk for UTI or in those with
high-grade reflux.27, 56
Surgical management

VUR can be corrected either by surgical


reimplantation of the ureter or endoscopic
injection of a bulking agent next to the vesicoureteral junction, with a reported resolution rate of 98.1% for open surgery (95% CI,
95.1 to 99.1) and 83.0% for endoscopic therapy (95% CI, 69.1 to 91.4) after a single injection.27, 57 Nevertheless, the American Urological Association guidelines 57 recommend
antibiotic prophylaxis rather than surgery for
all infants with VUR but children with higher
reflux grades and the presence of scarring.
AAP 29 and NICE 28 guidelines do not discuss the surgical management of UTIs.

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Imaging: renal and bladder ultrasonography (RBUS)

The AAP 29 suggests a different timing


of RBUS according to the clinical situation.
RBUS is recommended during the first 2
days of treatment when the clinical illness is
unusually severe or there is no evident clinical improvement, in order to identify serious complications such as renal or perirenal
abscesses or pyonephrosis associated with
obstructive uropathy. For febrile infants
with UTIs who clearly demonstrate clinical
improvement imaging does not need to occur early during the acute infection and can
even be misleading.
NICE guidelines 28 suggest to perform
RBUS of the urinary tract during the acute
infection only in children of all ages with
atypical UTI (see Table V for definition),
while suggest to perform RBUS within six
weeks of the infection in infants younger
than 6 months with first time UTI that is
responsive to treatment.
According to Montini et al.,27 after an uncomplicated first febrile UTI in a child under
3 years of age, the first step is to ascertain
whether a reliable, normal ultrasonographic
study performed during the third trimester
of pregnancy is available for review; if not,
RBUS could be performed. If the course of
a UTI is atypical, RBUS is indicated (agreeing with NICE guidelines).

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The best approach to evaluating a child


after a first febrile UTI is still an enormous
issue.
AAP 2011 guidelines 29 state that febrile
infants with UTIs should undergo RBUS
in order to detect anatomic abnormalities
that require further evaluation, such as additional imaging or urologic consultation
and to provide an evaluation of the renal
parenchyma and an assessment of renal
size that can be used to monitor renal
growth.
The rate of ultrasonographic detection of
grade III to V reflux ranges from 22%, when
only dilatation of the urinary tract is defined
as abnormal,22 to 67% 58 and 86%,59 when
other ultrasonographic abnormalities (renal
hypodysplasia, thickened bladder or pelvis
wall, or signs of pyelonephritis) are included.27 Nevertheless, this imaging technique
does not reliably detect low-grade reflux,
pyelonephritis, or scarring.22 In three trials
involving a total of 864 children, prospective US after an initial febrile UTI failed to
reliably detect changes associated with reflux or subsequent renal damage 24, 60, 61 and
had little influence on subsequent management. A systematic review 62 and a more
recent study 63 indicated that approximately
70% of renal and urinary tract anomalies
are already detected antenatally by means
of routine US performed during the second
and third trimesters of pregnancy, but the
consequences of prenatal screening with
respect to the risk of renal abnormalities in
infants with UTIs have not yet been well
defined.29

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(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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or other proprietary information of the Publisher.

BUONSENSO

Table V.Definition of atypical UTI.


Consider a UTI as atypical with any of the following
Septicaemia or seriously ill children
Poor urine flow
Abdominal or bladder mass
Raised creatinine concentration
Failure to respond to adequate treatment within 48
hours
Infection with an organism other than E. coli
Adapted from NICE guidelines.28

152

Imaging: VCUG

VCUG should not be performed routinely


after the first febrile UTI; VCUG is indicated
if RBUS reveals hydronephrosis, scarring,
or other findings that would suggest either
high-grade VUR or obstructive uropathy, as
well as in other atypical or complex clinical circumstances.28, 29 If prophylaxis is, as
already mentioned, not beneficial and VUR
is not required for development of pyelonephritis, then the rationale for performing
VCUG routinely after an initial febrile UTI
must be questioned.
The NICE algorithm for imaging studies
in children with UTI is shown in Table VI.
The validity of the NICE algorithm has
been recently highlighted by a retrospective review 64 comparing outcomes during
periods before algorithm use (September

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Table VI.The NICE algorithm for imaging studies after febrile UTIs.28
Responds well to therapy by 48 h
Not atypical or recurrent UTI

Study

Atypical UTI

History of
prior UTI

Yes
No
No
Yes

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Age <6 months


US acutely
No
Yes
US within 6 wk
Yes
No
VCUG
Only if US is abnormal, atypical UTI, or history of prior UTI
Age >6 months but <3 years
US acutely
No
Yes
US within 6 wk
No
No
VCUG
Only if US is abnormal, poor urine flow, nonEscherichia coli
infection, or family history of reflux
Age >3 years
Study
Responds well to Rx by 48 h Not atypical or recurrent UTI
Atypical UTI
US acutely
US within 6 wk
VCUG

No
No
Only if US is abnormal

1, 2006, to August 31, 2007) and after algorithm use (September 1, 2008, to August
31, 2009). Schroeder et al noted a dramatic
reduction in VCUGs following a febrile UTI
under the selective algorithm from 99%
down to 13% and a lesser but still significant decrease in RBUS (from 99% to 67%).
They demonstrated no significant difference in cases of grades 4 and 5 VUR identified. A reduction in antibiotic prophylaxis
from 27% to 3%, primarily due to lack of
detection of lesser grades of VUR, was not
associated with an increased incidence of
recurrent UTI. The authors concluded that
by restricting urinary tract imaging after
an initial febrile UTI, rates of VCUG and
prophylactic antibiotic use decreased substantially without increasing the risk of UTI
recurrence within 6 months and without
an apparent decrease in detection of highgrade VUR.
This selective approach reduces the
cost and distress associated with the procedure (which necessitates instillation of
a radiopaque, radioactive, or echocontrast
medium into the bladder through urethral
catheterization, followed by serial imaging
during filling and voiding) in children with
an uncomplicated first febrile UTI who are
otherwise well. However, the selective approach may miss a number of children who
have clinically important reflux until another infection occurs.16, 27, 28

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(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.

URINARY TRACT INFECTIONS IN CHILDREN

Vol. 64 - No. 2

Yes
No

History of
prior UTI
No
Yes

Imaging: renal scintigraphy

Renal scintigraphy with 99mTc-dimercaptosuccinic acid (DMSA) performed during the acute phase of a UTI, followed by
VCUG if the scintigraphic examination suggests pyelonephritis (once a urine culture is
negative), has been referred to as the top
down approach 65, 66 and focuses on putative pyelonephritis and scarring. This approach may decrease the number of VCUG
examinations performed.
Some expertise recommend renal scintigraphy 6 to 12 months after an acute infection to detect the formation of scarring,
which would require follow-up.61, 67 In
particular, Zaffanello et al.68 prospectively
evaluated children who had experienced
the first febrile UTI at or under the age of 2
years with normal fetal routine ultrasound.
All the children underwent renal ultrasound
after admission; those with sonographic
signs of obstruction were excluded. VCUG
and DMSA scintigraphy were performed
approximately 1 month and 6 months after
the UTI, respectively. VUR was detected in
55.4% of the children and renal scarring in
18.5%. The severity of VUR correlated significantly with renal scarring. The authors
concluded that follow-up renal scintigraphy 6 months after a UTI can predict severe VUR in very young children showing
renal scarring, detecting only those who are

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URINARY TRACT INFECTIONS IN CHILDREN

at risk of loss of kidney function and who


would require further assessment.
NICE guidelines 29 suggest to perform a
DMSA scan 4-6 months after the acute infection to detect renal parenchymal defects
only in children younger than 3 years with
atypical and/or recurrent UTI.

Pathogens other than E. Coli. P fimbriated E. coli bind to uroepithelial cells and
resist to the normal urine flow. Non fimbriated bacteria ascend the urinary tract with
the help of obstruction or reflux.
In a child with an abnormal US or the
presence of one of the previous risk factors, the Italian Guidelines 50 suggest further
imaging of the urinary tract (cystography)
and the renal parenchyma. In all children
with an abnormal US or in whom VUR has
been shown, a renal cortical scintigraphy
(with DMSA) is recommended 6 months
after the febrile UTI, in order to obtain a
morphologic (presence of UTI related renal
scarring) and functional evaluation (relative
renal function) of the renal parenchyma. In
children with febrile UTI presenting none
of the risk factors discussed above no further imaging of the urinary tract and of the
renal parenchyma is recommended. In case
of recurrence of febrile UTIs, cystography
and renal DMSA scan should be performed.

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When should further renal imaging


(after RBUS) be performed?
The new Italian Guidelines

According to the new Italian Guidelines,50 if RBUS is normal and no risk factors are present, further imaging is not indicated. If RBUS shows abnormalities or risk
factors are present a complete morphologic
evaluation of the kidney and urinary tract
is indicated.
Suggested risk factors include:
In utero or postnatal US abnormalities: hydronephrosis, ureteral dilatation,
duplicated system, renal hypoplasia, loss
of cortico-medullary differentiation or abnormal parenchymal echogenicity, bladder
wall thickening or irregularity, post-micturating abnormal residual urine volume, bladder diverticula.
Family history of VUR: from a recent
meta-analysis the prevalence of VUR is
27.4% (range 2.9-51.9) in siblings and 35.7%
(range 16.4-61) in offspring screened.
Septicemia: UTI is associated with
sepsis in about 10% of infants. When sepsis
is present the risk of urologic abnormalities
is higher.
Renal failure.
Male infants less than 6 months of
age.
Suspicion of noncompliance of the
family, which requires a more stringent diagnostic approach, in order to avoid dropouts and the loss to follow-up of children
which could be at risk of renal damage.
Micturition abnormalities or thickened
bladder wall which may indicate posterior
urethral valves.
Absence of a clinical response to antibiotics within 72 hours, with persistence
of fever.

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(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.

BUONSENSO

154

Conclusions

The management of febrile UTIs in children is changing and daily challenging clinicians. A definitive approach cannot be
suggested yet, overall regarding the best
management of children after a first UTI.
On one hand, the concept of primary renal
damage is growing as improved prenatal
ultrasonography has revealed that major
kidney damage in children is frequently related to the presence of hypodysplasia, associated with urologic abnormalities; on the
other hand, infection-related renal scarring
develops in some children, causing further
damage in dysplastic kidneys, with the potential for late effects in previously normal
kidneys.
In our opinion, the new Italian Guidelines 50 and NICE guidelines 28 represents
currently the best approach in the management of UTIs in children, with the only adjunction for NICE guidelines to consider a
renal scintigraphy 6 to 12 months after a
UTI in order to predict severe VUR in very
young children showing renal scarring, de-

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BUONSENSO

tecting those children who are at risk of loss


of kidney function and who would require
further assessment. The value of antibiotic
prophylaxis has been questioned, but ongoing studies may help to answer these
questions.
Riassunto

9. Normand IC, Smellie JM. Prolonged maintenance


chemotherapy in the management of urinary infection in childhood. Br Med J 1965;1:1023-6.
10. Politano VA, Leadbetter WF. An operative technique
for the correction of vesicoureteral reflux. J Urol
1958;79:932-41.
11. Prospective trial of operative versus non-operative
treatment of severe vesicoureteric reflux: two years
observation in 96 children. Br Med J (Clin Res Ed)
1983;287:171-4.
12. Medical versus surgical treatment of primary vesicoureteral reflux: report of the International Reflux
Study Committee. Pediatrics 1981;67:392-400.
13. National Institute for Health and Clinical Excellence.
Urinary tract infection in children: diagnosis, treatment and longterm management [Internet]. Available
at http://www.nice.org.uk/nicemedia/pdf/CG54fullguideline.pdf [cited 2012, Feb 23].
14. Royal Childrens Hospital Melbourne. Clinical practice guidelines [Internet]. Available at http://www.
rch.org.au/clinicalguide/cpg.cfm?doc_id=5241) [cited
2012, Feb 23].
15. Hannula A, Venhola M, Renko M, Pokka T, Huttunen
NP, Uhari M. Vesicoureteral reflux in children with
suspected and proven urinary tract infection. Pediatr
Nephrol 2010;25:1463-9.
16. Marks SD, Gordon I, Tullus K. Imaging in childhood
urinary tract infections: time to reduce investigations.
Pediatr Nephrol 2008;23:9-17.
17. Mori R, Lakhanpaul M, Verrier-Jones K. Diagnosis and
management of urinary tract infection in children:
summary of NICE guidance. BMJ 2007;335:395-7.
18. Moorthy I, Easty M, McHugh K, Ridout D, Biassoni L,
Gordon I. The presence of vesicoureteric reflux does
not identify a population at risk for renal scarring following a first urinary tract infection. Arch Dis Child
2005;90:733-6.
19. Venhola M, Hannula A, Huttunen NP, Renko M, Pokka T, Uhari M. Occurrence of vesicoureteral reflux in
children. Acta Paediatr 2010;99:1875-8.
20. Keren R. Imaging and treatment strategies for children after first urinary tract infection. Curr Opin Pediatr 2007;19:705-10.
21. Merguerian PA, Sverrisson EF, Herz DB, McQuiston
LT. Urinary tract infections in children: recommendations for antibiotic prophylaxis and evaluation: an
evidencebased approach. Curr Urol Rep 2010;11:98108.
22. Hoberman A, Charron M, Hickey RW, Baskin M,
Kearney DH, Wald ER. Imaging studies after a first
febrile urinary tract infection in young children. N
Engl J Med 2003;348:195-202.
23. Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R. Recurrent urinary tract infections
in children: risk factors and association with prophylactic antimicrobials. JAMA 2007;298:179-86.
24. Garin EH, Olavarria F, Garcia Nieto V, Valenciano B,
Campos A, Young L. Clinical significance of primary
vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: amulticenter, randomized, controlled study. Pediatrics 2006;117:62632.
25. Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A, Gobber D et al. IRIS Group. Prophylaxis after
first febrile urinary tract infection in children? a multicenter, randomized, controlled, noninferiority trial.
Pediatrics 2008;122:1064-71.
26. Pennesi M, Travan L, Peratoner L, Bordugo A, Cattaneo A, Ronfani L et al. North East Italy Prophylaxis
in VUR Study Group. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing

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Infezioni del tratto urinario nei bambini: una review


La pielonefrite rappresenta la pi frequente infezione grave in et pediatrica, tuttavia non ancora
chiaro quale sia la sua migliore gestione, soprattutto riguardo al follow-up in seguito a un primo
episodio febbrile di infezione delle vie urinarie. In
questo articolo verranno riassunte le attuali raccomandazioni per la diagnosi, il trattamento, limaging
e luso della profilassi antibiotica per i bambini con
un primo episodio febbrile di infezione delle vie
urinarie. Tuttavia, lo sviluppo di un unico protocollo diagnostico universalmente accettato sembra
ancora lontano.
Parole chiave: Tratto urinario, infezioni - Bambino
- Ultrasonografia.

References

1. Hellstram A, Hanson E, Hansson S, Hj.lm.s K, Jodal U.


Association between urinary symptoms at 7 years old
and previous urinary tract infection. Arch Dis Child
1991;66:232-4.
2. Marild S, Jodal U. Incidence rate of first-time symptomatic urinary tract infection in children under 6 years
of age. Acta Paediatr 1998;87:549-52.
3. American Academy of Pediatrics, Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. The diagnosis, treatment, and evaluation of
the initial urinary tract infection in febrile infants and
young children. Pediatrics 1999;103:843-52. [Errata,
Pediatrics 1999;103:1052, 104:118, 2000;105:141.]
4. Jakobsson B, Svensson L. Transient pyelonephritic
changes on 99mTechnetium- dimercaptosuccinic
acid scan for at least five months after infection. Acta
Paediatr 1997;86:803-7.
5. Winter AL, Hardy BE, Alton DJ, Arbus GS, Churchill BM. Acquired renal scars in children. J Urol
1983;129:1190-4.
6. Smellie JM, Poulton A, Prescod NP. Retrospective
study of children with renal scarring associated with
reflux and urinary infection. BMJ 1994;308:1193-6.
7. Pistor K, Sch.rer K, Olbing H, Tamminen-M.bius T.
Children with chronic renal failure in the Federal Republic of Germany. II. Primary renal diseases, age
and intervals from early renal failure to renal death:
Arbeitsgemeinschaft fur Padiatrische Nephrologie.
Clin Nephrol 1985;23:278-84.
8. Deluca FG, Fisher JH, Swenson O. Review of recurrent urinary-tract infections in infancy and early
childhood. N Engl J Med 1963;268:75-7.

This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.

URINARY TRACT INFECTIONS IN CHILDREN

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MINERVA PEDIATRICA

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URINARY TRACT INFECTIONS IN CHILDREN

45. Jodal U, Smellie JM, Lax H, Hoyer PF. Ten-year results


of randomized treatment of children with severe vesicoureteral reflux: final report of the International Reflux Study in Children. Pediatr Nephrol 2006;21:78592.
46. Smellie JM, Barratt TM, Chantler C, Gordon I, Prescod
NP, Ransley PG et al. Medical versus surgical treatment in children with severe bilateral vesicoureteric
reflux and bilateral nephropathy: a randomized trial.
Lancet 2001;357:1329-33.
47. Medscape from WebMD. Drugs, OTCs & Herbals.
Application v2.4.1. Drug reference v938.0 Accessed
22/11/11.
48. Craig JC, Simpson JM, Williams GJ, Lowe A, Reynolds
GJ, McTaggart SJ et al. Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric
Reflux and Normal Renal Tracts (PRIVENT) Investigators. N Engl J Med 2009; 361: 1748-59.
49. Brandstrm P, Esbjrner E, Herthelius M, Swerkersson S, Jodal U, Hansson S. The Swedish reflux trial
in children: III. Urinary tract infection pattern. J Urol
2010; 184:286-91.
50. Ammenti A, Cataldi L, Chimenz R, et al.
Febrile Urinary Tract Infections in young children. Recommendations for the diagnosis, treatment and follow-up.
Acta Paediatr. 2011 Nov 28. doi: 10.1111/j.16512227.2011.02549.x. [Epub ahead of print]
51. Keren R, Carpenter MA, Hoberman A, Shaikh N,
Matoo TK, Chesney RW et al. Rationale and design
issues of the Randomized Intervention for Children
With Vesicoureteral Reflux (RIVUR) study. Pediatrics
2008;122(Suppl 5):S240-S250.
52. Guay DR. Cranberry and urinary tract infections.
Drugs 2009;69:775-807.
53. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev
2008;1:CD001321.
54. Ferrara P, Romaniello L, Vitelli O, Gatto A, Serva M,
Cataldi L. Cranberry juice for the prevention of recurrent urinary tract infections: a randomized controlled
trial in children. Scand J Urol Nephrol 2009;43:1-5.
55. Wiswell TE, Smith FR, Bass JW. Decreased incidence
of urinary tract infections in circumcised male infants.
Pediatrics 1985;75:901-3.
56. Singh-Grewal D, Macdessi J, Craig J. Circumcision for
the prevention of urinary tract infection in boys: a
systematic review of randomised trials and observational studies. Arch Dis Child 2005;90:853-8.
57. American Urological Association. Clinical guidelines
[Internet]. Available at http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.
cfm?sub=vur2010 [cited 2012, Feb 23].
58. Lee MD, Lin CC, Huang FY, Tsai TC, Huang CT, Tsai
JD. Screening young children with a first febrile urinary tract infection for high-grade vesicoureteral reflux with renal ultrasound scanning and technetium99m-labeled dimercaptosuccinic acid scanning. J
Pediatr 2009;154:797-802.
59. Lee HY, Soh BH, Hong CH, Kim MJ, Han SW. The
efficacy of ultrasound and dimercaptosuccinic acid
scan in predicting vesicoureteral reflux in children
below the age of 2 years with their first febrile urinary tract infection. Pediatr Nephrol 2009;24:2009-13.
60. Zamir G, Sakran W, Horowitz Y, Koren A, Miron D.
Urinary tract infection: is there a need for routine
renal ultrasonography? Arch Dis Child 2004;89:466-8.
61. Montini G, Zucchetta P, Tomasi L, Talenti E, Rigamonti W, Picco G et al. Value of imaging studies after
a first febrile urinary tract infection in young children:
data from Italian renal infection study 1. Pediatrics
2009;123:e239-e246.

IN
C ER
O V
P A
Y
R M
IG E
H DI
T C
A

pyelonephritis and renal scars? a randomized, controlled trial. Pediatrics 2008;121:e1489-e1494.


27. Montini G, Tullus K, Hewitt I. Febrile urinary tract infections in children. N Engl J Med. 2011;365(3):239-50
28. National Institute for Health and Clinical Excellence.
Urinary Tract Infection in Children. London, England:
National Institute for Health and Clinical Excellence;
August 2007. NICE clinical guideline 54 [Internet]
Available at http://www.nice.org.uk/nicemedia/pdf /
CG54NICEguideline.pdf [cited 2011, Nov 9].
29. Subcommittee on Urinary Tract Infection and Steering Committee Quality Improvement and Management. Urinary tract infection. Pediatrics 2011;28:595610.
30. Pryles CV, Atkin MD, Morse TS, Welch KJ. Comparative bacteriologic study of urine obtained from children by percutaneous suprapubic aspiration of the
bladder and by catheter. Pediatrics 1959;24:983-91.
31. Kramer MS, Tange SM, Drummond KN, Mills EL.
Urine testing in young febrile children: a risk-benefit
analysis. J Pediatr 1994;125:6-13.
32. Bonadio WA. Urine culturing technique in febrile infants. Pediatr Emerg Care 1987;3:75-8.
33. Taylor CM, White RH. The feasibility of screening
preschool children for urinary tract infection using
dipslides. Int J Pediatr Nephrol 1983;4:113-4.
34. Srensen K, Lose G, Nathan E. Urinary tract infections and diurnal incontinence in girls. Eur J Pediatr
1988;148:146-7.
35. Shannon F, Sepp E, Rose G. The diagnosis of bacteriuria by bladder puncture in infancy and childhood.
Aust Pediatr J 1969;5:97-100
36. Lohr J. Pediatric Outpatient Procedures. Philadelphia,
PA: Lippincott; 1991
37. UTI Guideline Team, Cincinnati Childrens Hospital
Medical Center: Evidence-based care guideline for
medical management of first urinary tract infection in
children 12 years of age or less. Guideline 7, pages
1-23, November, 2006 [Internet]. Available at http://
www.cincinnatichildrens.org/svc/dept-div/healthpolicy/ev-based/uti.htm [cited 2011, Nov 24].
38. Li YH, Yan ZQ, Brauner A, Tullus K. Activation of
macrophage nuclear factorkappa B and induction
of inducible nitric oxide synthase by LPS. Respir Res
2002;3:23.
39. Tullus K, Escobar-Billing R, Fituri O, Lu Y, Brauner A.
Soluble receptors to tumour necrosis factor and interleukin-6 in urine during acute pyelonephritis. Acta
Paediatr 1997;86:1198-202.
40. Hussein A, Askar E, Elsaeid M, Schaefer F. Functional
polymorphisms in transforming growth factor-beta-1
(TGFbeta-1) and vascular endothelial growth factor
(VEGF) genes modify risk of renal parenchymal scarring following childhood urinary tract infection. Nephrol Dial Transplant 2010;25:779-85.
41. Ismaili K, Wissing KM, Lolin K, Le PQ, Christophe
C, Lepage P, Hall M. Characteristics of First Urinary
Tract Infection With Fever in Children: A Prospective Clinical and Imaging Study. Pediatr Infect Dis J
2011;30:371-4.
42. Montini G, Hewitt I. Urinary tract infections: to
prophylaxis or not to prophylaxis? Pediatr Nephrol
2009;24:1605-9.
43. Prelog M, Schiefecker D, Fille M, Wurzner R, Brunner A, Zimmerhackl LB. Febrile urinary tract infection in children: ampicillin and trimethoprim insufficient as empirical mono-therapy. Pediatr Nephrol
2008;23:597-602.
44. Chakupurakal R, Ahmed M, Sobithadevi DN, Chinnappan S, Reynolds T. Urinary tract pathogens and
resistance pattern. J Clin Pathol 2010;63:652-4.

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acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol
2004;172:1071-4.
66. Preda I, Jodal U, Sixt R, Stokland E, Hansson S. Normal dimercaptosuccinic acid scintigraphy makes
voiding cystourethrography unnecessary after urinary tract infection. J Pediatr 2007;151:581-4.
67. Stefanidis CJ, Siomou E. Imaging strategies for
vesicoureteral reflux diagnosis. Pediatr Nephrol
2007;22:937-47.
68. Zaffanello M, Cataldi L, Brugnara M, Franchini M,
Bruno C, Fanos V. Hidden high-grade vesicoureteral
reflux is the main risk factor for chronic renal damage in children under the age of two years with
first urinary tract infection. Scand J Urol Nephrol
2009;43:494-500.

IN
C ER
O V
P A
Y
R M
IG E
H DI
T C
A

62. Bricker L, Garcia J, Henderson J, Mugford M, Neilson


J, Roberts T et al. Ultrasound screening in pregnancy:
a systematic review of the clinical effectiveness, costeffectiveness and womens views. Health Technol Assess 2000;4:1-193.
63. Bhide A, Sairam S, Farrugia MK, Boddy SA, Thilaganathan B. The sensitivity of antenatal ultrasound
for predicting renal tract surgery in early childhood.
Ultrasound Obstet Gynecol 2005;25:489-92.
64. Schroeder AR, Abidari JM, Kirpekar R, Hamilton
JR, Kang YS, Tran V et al. Impact of a more restrictive approach to urinary tract imaging after febrile
urinary tract infection. Arch Pediatr Adolesc Med
2011;165:1027-32.
65. Hansson S, Dhamey M, Sigstrm O, Sixt R, Stokland E, Wennerstrm M et al. Dimercapto-succinic

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