Contemporary Management of Urinary

Tract Infection in Children

Tej K. Mattoo, MD, DCH, FRCP, FAAP,a Nader Shaikh, MD,b Caleb P. Nelson, MD, MPHc

Urinary tract infection (UTI) is common in children, and girls are at abstract
a significantly higher risk, as compared to boys, except in early infancy. Most
cases are caused by Escherichia coli. Collection of an uncontaminated urine
specimen is essential for accurate diagnosis. Oral antibiotic therapy for 7 to
10 days is adequate for uncomplicated cases that respond well to the
treatment. A renal ultrasound examination is advised in all young children
with first febrile UTI and in older children with recurrent UTI. Most children
with first febrile UTI do not need a voiding cystourethrogram; it may be
considered after the first UTI in children with abnormal renal and bladder
a
ultrasound examination or a UTI caused by atypical pathogen, complex Division of Pediatric Nephrology, Departments of Pediatrics
and Urology, Wayne State University School of Medicine and
clinical course, or known renal scarring. Long-term antibiotic prophylaxis is Wayne Pediatrics, Detroit, Michigan; bDepartment of
used selectively in high-risk patients. Few patients diagnosed with Pediatrics, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania; and cDepartment of Urology,
vesicoureteral reflux after a UTI need surgical correction. The most Boston Children’s Hospital and Department of Surgery,
consequential long-term complication of acute pyelonephritis is renal Harvard Medical School, Harvard University, Boston,
Massachusetts
scarring, which may increase the risk of hypertension or chronic kidney
disease later in life. Treatment of acute pyelonephritis with an appropriate Dr Mattoo conceptualized and formatted the
antibiotic within 48 hours of fever onset and prevention of recurrent UTI manuscript template, drafted the initial manuscript,
and reviewed and revised the manuscript; Drs
lowers the risk of renal scarring. Pathogens causing UTI are increasingly Nelson and Shaikh participated in formatting the
becoming resistant to commonly used antibiotics, and their indiscriminate initial manuscript, drafted sections of the initial
use in doubtful cases of UTI must be discouraged. manuscript, and reviewed and revised the
manuscript; and all authors approved the final
manuscript as submitted and agree to be
accountable for all aspects of the work.
DOI: https://doi.org/10.1542/peds.2020-012138
Urinary tract infection (UTI) is one of common organisms include Klebsiella,
the most common bacterial infections Proteus, Enterococcus, and Enterobacter Accepted for publication Sep 4, 2020
in childhood. In the first year of life, it is species.9–11 Organisms such as Address correspondence to Tej K. Mattoo, MD, Wayne
more common in boys (3.7%), as Pseudomonas, group B Streptococcus, Pediatrics, 400 Mack Ave, Suite 1 East, Detroit, MI
48201. E-mail: tmattoo@med.wayne.edu
compared to girls, (2%) and after and Staphylococcus aureus are usually
infancy, it is significantly more associated with CAKUT, genitourinary PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
prevalent in girls. During prepubertal surgery, a foreign body (eg, catheter),
age, the incidence in girls is 3%, as or recent antibiotic treatment, whereas Copyright © 2021 by the American Academy of
Pediatrics
compared to 1% in boys.1–3 The risk of infection with urea-splitting organisms
UTI recurrence in the first 6 to (eg, Proteus) is associated with stone FINANCIAL DISCLOSURE: The authors have indicated
they have no financial relationships relevant to this
12 months after the initial UTI is ∼12% formation.8,12 Prompt diagnosis and article to disclose.
to 30%.4,5 Besides sex, other significant treatment are important for the
FUNDING: No external funding.
risk factors for UTI are bladder-bowel prevention of acute complications as
dysfunction (BBD); congenital well as renal scarring. In the last 2 POTENTIAL CONFLICT OF INTEREST: The authors have
indicated they have no potential conflicts of interest
anomalies of kidneys and the urinary decades, a significant amount of to disclose.
tract (CAKUT), including vesicoureteral research has been done on UTI in
reflux (VUR); and the circumcision children, particularly on renal imaging
To cite: Mattoo TK, Shaikh N, Nelson CP.
status in young boys.4,6–8 and long-term antibiotic prophylaxis Contemporary Management of Urinary Tract
Approximately 85% to 90% of UTIs are after UTI. The objective of this review is Infection in Children. Pediatrics. 2021;147(2):
caused by Escherichia coli. Other to summarize the current literature on e2020012138

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PEDIATRICS Volume 147, number 2, February 2021:e2020012138 STATE-OF-THE-ART REVIEW ARTICLE
UTI in children, with an emphasis on
its clinical management.
DEFINITIONS OF COMMONLY USED
TERMS IN UTI
The definitions that are often used in
association with UTI relate to its
clinical presentation, site and severity
of infection, frequency of UTI, and the
occurrence of renal scarring.
Frequently used definitions are
elaborated in Table 1.
PATHOGENESIS OF ACUTE
PYELONEPHRITIS AND RENAL SCARRING
The pathogenesis of acute
pyelonephritis (APN) and renal
scarring is complex and not fully
understood. Most UTIs are ascending
infections that start with periurethral
colonization; hematogenous spread
occurs primarily in debilitated,
obstructed, or immunocompromised
patients, and these are mostly fungal
and staphylococcal infections.13 The
virulence of uropathogenic E coli is
largely influenced by the presence of P
fimbriae, also known as pyelonephritis-
associated pili, and lipopolysaccharide.
The binding of the P fimbriae to
epithelial cells is mediated by the tip
adhesin PapG. Bacterial
lipopolysaccharide is important for the
initiation of tissue inflammation. It is
bound in the kidney by toll-like
receptor 4, which is a transmembrane
protein and a member of the toll-like
receptor family. These receptors are
present on the epithelial cells and parts
of the renal tubule. Their activation
leads to a release of proinflammatory
cytokines and chemokines and the
recruitment of neutrophils.14,15
Lipopolysaccharide also activates the
recruited macrophages. The presence
of macrophages, dendritic cells, and
T cells in renal interstitium induces
inflammation via modulation of
immune response through recruitment
and activation of neutrophils16 and the
generation of reactive oxygen species,
resulting in killing the pathogen.
The fibrosis and scarring that follows is
initiated by macrophages and
conducted by neutrophils.17 Monocyte
chemoattractant protein-1, which is
secreted by kidney epithelial cells,
recruits monocytes at the site of
infection. Monocytes differentiate into
2 groups of macrophages:
proinflammatory monocytes that kill
the pathogen by secreting
inflammatory cytokines (such as
interleukins and tumor necrosis factor
a) as well as cytotoxic reagents (such
as nitric oxide synthase and reactive
oxygen species) and anti-inflammatory
monocytes that terminate the
inflammatory response. Depending on
the severity of kidney damage, the
latter also induces kidney fibrosis
through transforming growth factor b.
The proinflammatory response, which
is necessary for killing the pathogen,
also damages the surrounding tissue,
causing tissue ischemia, tubular cell
death, and reperfusion injury. The
fibrosis and scarring that follows is
initiated by macrophages.16,18–20
RISK FACTORS FOR UTI
The important risk factors for UTI in
children are female sex (or
uncircumcised infant boy), younger
age, white race, high-grade VUR,
CAKUT, BBD, and instrumentation of
the urinary tract (particularly
indwelling bladder
catheterization).2,4,21–23 Other risk
factors for UTI in older children and
adolescents include the presence of
kidney stones, sexual activity, and
diabetes. Genetic factors also influence
the occurrence of UTI.24 Administration
of an antibiotic may increase the risk of
UTI by changing periurethral
microflora.25 A calculator was recently
developed to help clinicians estimate
the probability of UTI in febrile infants
at the bedside (https://uticalc.pitt.
edu).26 It is based on 5 risk factors that
include age ,12 months, white race,

TABLE 1 Frequently Used Terms for UTI

Category Term Definition
Signs and Febrile UTI UTI associated with temperature $38°C (100.4°F)
symptoms
Symptomatic UTI UTI associated with fever and/or urinary symptoms
ABU Significant bacteriuria in a child with no symptoms of UTI
Sterile pyuria Increased white cells in urine in the absence of bacteria on urine culture
BBD Spectrum of signs and symptoms, including incontinence, constipation and/or encopresis associated with functional
and behavioral abnormalities of the bowel, lower urinary tract, and pelvic floor
Site of infection Upper-tract UTI UTI involving kidneys and ureters
Lower-tract UTI UTI involving bladder and urethra but not upper tract
Pyelonephritis Kidney infection (febrile UTI may or may not be due to pyelonephritis)
Cystitis Bladder infection
Severity of Complicated UTI UTI in newborns; abdominal and/or bladder mass; kidney and urinary tract anomalies; urosepsis; organism other than
infection E coli; atypical clinical course, including absence of clinical response to antibiotic within 72 h; and renal abscess
Complicated Children with comorbid medical conditions, underlying bladder pathology, indwelling bladder catheter, and atypical
cystitis clinical course
Renal status Reflux Renal cortical abnormalities associated with VUR (may be congenital dysplasia or acquired scarring)
nephropathy
Renal scarring Acquired renal damage due to APN
Renal dysplasia Congenital renal cortical abnormalities

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2 MATTOO et al
female sex (or uncircumcised boy),
maximum temperature .39°C, and the
absence of another source for fever.
The calculator was validated in
a cohort of .2000 children and was
found to reduce unnecessary testing,
decrease missed UTIs, and reduce
treatment delays. Bubble baths may
infrequently cause irritation and
discomfort of the genital mucosa and
periurethral tissue in children,27 which
may be wrongly interpreted as a UTI:
there is little evidence that the bubble
baths actually cause UTI.28
RISK FACTORS FOR RENAL SCARRING
A number of risk factors are
associated with acquired renal
scarring due to APN. These include
a high grade of VUR (grades .2 and
particularly grades 4 and 5),7,29
duration of fever of .72 hours before
antibiotic initiation,30–32 recurrent
UTI,29,33–35 and organisms other than
E coli.36–38 Previously, a young age was
considered to be a risk factor, but
recent studies have revealed that older
children may be at higher risk of renal
scarring29,36,39; the discrepancy may
be related to the inadvertent inclusion
of patients with preexisting congenital
scarring (renal dysplasia) in the
earlier studies because differentiation
between congenital and acquired
scarring after APN is challenging,
particularly when baseline (ie, pre-
UTI) studies are not available. In
comparison with the other pathogens,
infection with P fimbriae E coli
increases the probability of ascending
infection but does not appear to be
associated with increased
dimercaptosuccinic acid (DMSA) renal
scan abnormalities.40 It has long
been speculated that there is
a genetic predisposition in some
children to develop renal scarring
after APN. Polymorphisms of the
HSPA1B gene of HSP72 protein were
found to be associated with renal
scarring,41 whereas variants of the
toll-like receptor 4 gene were
associated with renal scarring in
another study.42 In other studies,
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PEDIATRICS Volume 147, number 2, February 2021
researchers have indicated potential
roles for polymorphisms of the
angiotensin-converting enzyme and
transforming growth factor b1
genes.43 In studies of plasminogen
activator inhibitor 1, researchers
found that it was not associated with
risk of renal scarring among infants
after first febrile UTI.44
DIAGNOSIS OF UTI
A targeted history and physical
examination and positive urinary
findings are essential for an accurate
diagnosis of UTI.
• History and physical examination:
In older, verbal children, important
findings include dysuria, urgency
and/or frequency, abdominal or
flank pain, and new-onset
• Urinalysis: Antibiotic treatment of
incontinence.45 In contrast, signs
and symptoms of UTI in infancy are
nonspecific, and fever may be the
only symptom, although neonates
may present with hypothermia.
History of constipation, UTI in
siblings or parents, and recent
infections or antibiotic treatment
should be ascertained. Relevant
signs on abdominal examination
include distention, presence of
a mass or palpable stool, flank or
suprapubic tenderness, and/or
a palpable bladder, particularly after
voiding.
• Urine specimen: In non–toilet-
trained children, urine collection
method has a profound significance
for diagnosis of UTI. Urine specimen
in such children should be collected
preferably by ureteral
catheterization or suprapubic
bladder aspiration, particularly if
a specimen collected by perineal bag
is dipstick-positive. In a recent video
published in the New England
Journal of Medicine, researchers
• Urine culture: The acceptable
reviewed the methods of suprapubic
aspiration.46 Another reasonable
alternative is the Quick-Wee method
of urine collection.47 In this method,
the suprapubic area is stimulated by
using a gauze soaked in cold fluid,
and the voided midstream urine is
caught in a sterile cup.48 Regardless
of the technique, contamination of
voided specimens from infants is
a significant concern, particularly for
girls and uncircumcised, young boys.
In older, toilet-trained children,
a urine specimen can be obtained by
catching the midstream urine in
a sterile cup after cleaning of skin
around the genital area; girls may
benefit from facing backward on the
toilet, which splays the legs and labia
and may reduce contamination from
skin and vaginal surfaces. In
uncircumcised boys, gentle
retraction of the prepuce (if possible)
is important to obtain an
uncontaminated specimen, and urine
from boys with significant phimosis
is likely to be contaminated.
UTI is often started empirically
because urine culture results take 1
to 2 days. The leukocyte esterase
test on urine dipstick is the most
widely available screening test. The
results are usually reported
semiquantitatively (negative, trace,
11, 21, and 31). The accuracy of
currently available screenings tests
for UTI is summarized in Table 2.49
The table also demonstrates that
the currently available bedside
tests have a high rate of false-
positive and negative results with
treatment implications. A
microscopic urinalysis has only
marginally better accuracy than the
dipstick. Until better and more
accurate biomarkers for UTI
become available, the limitation of
bedside UTI screening should be
kept in mind and used only in
conjunction with clinical
assessment. Blood and/or protein
on urine dipstick examination are
poor indicators of UTI.
colony count threshold for a urine
culture positive for UTI depends on
its collection method. It is
50 000 colony-forming units
(CFUs)/mL for samples obtained by
3
TABLE 2 Accuracy of Widely Available Bedside Tests for UTI in a Hypothetical Cohort of 1000 Children
Tested for UTI
Sensitivity, Specificity,
% %
Leukocyte esterase 79 87
Nitrite 49 98
Leukocyte esterase or 88 79
nitrite
a Assuming a prevalence of 7.5% (ie, 75 with UTI and 925 with no UTI).2,45
catheterization, 100 000 for
samples obtained by clean catch,
and 1000 CFU/mL on samples
obtained by suprapubic aspiration.
The 2011 American Academy of
Pediatrics (AAP) guideline defines
UTI by the presence of at least
50 000 CFU/mL of a uropathogen
in a specimen obtained by bladder
catheterization in a child with
either a positive result on
a leukocyte esterase test or with
white blood cells in the urine on
microscopy (ie, pyuria).34 However,
requiring pyuria for diagnosis has
recently been questioned because of
the relatively low accuracy of pyuria
or the leukocyte esterase test,
reportedly low prevalence of
asymptomatic bacteria,50 and the
relatively low rate of contamination
in samples obtained by using
a urinary catheter. Another recent
finding that further complicates
matters is that UTI with different
organisms may be associated with
different degrees of pyuria;
Enterococcus species, Klebsiella
species, and Pseudomonas species in
particular seem to have a proclivity
to cause infection in the absence of
pyuria.51 Also controversial is the
use of a single colony count
threshold for all children.52 Several
studies have revealed that some
children with lower colony counts
have true UTIs and even
pyelonephritis.53 As such, the
definition of UTI is likely to continue
to evolve as new data emerge. In the
meantime, we recommend using the
AAP guideline, in combination with
clinical judgement, to determine the
likely diagnosis.
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4 MATTOO et al
No. Unnecessary No. With Delayed or
Antibiotic Missed Diagnosisa
Prescriptionsa
120 16
18 38
194 9
• Blood tests: Blood tests, such as
complete blood counts, serum
chemistry, and renal function tests,
are not routinely needed for
patients with UTI and should be
done only if clinically indicated.
COMMON ERRORS IN THE DIAGNOSIS
OF UTI
• Contaminated urine specimen: A
diagnosis of UTI based on
contaminated urine specimen may
lead to unnecessary antibiotic
treatment or delayed treatment in
those with true UTIs. The
contamination rates of bag urine
specimens can be as high as
80%.34,54 The 2 most common
sources of urine contamination are
feces and skin that it may come in
contact with while passing through
the vagina or under the foreskin.
Presence of $10 per high-power
field squamous epithelial cells on
urinalysis,55 insignificant bacterial
colony count, or the presence of $2
pathogens on urine culture in
midstream urine specimen is
suggestive of contamination.55
Growth of nonuropathogens such
as Lactobacillus, Corynebacterium,
viridans streptococci, or coagulase-
negative staphylococci such as
Staphylococcus epidermidis are
considered as contaminants in
children.34
• Asymptomatic bacteriuria (ABU):
Colonization of the bladder in the
absence of an inflammatory reaction
occurs at all ages, including infants
and children. ABU is more common
in girls and generally involves Gram-
negative bacteria, such as E coli. Its
reported incidence is ∼1% to 3%,
and it usually resolves
spontaneously in a few months to
a couple of years, although in some
girls, it may persist for much
longer.56–58 A recent meta-analysis
of published literature reported
a lower prevalence of ABU of
,0.5%.50 Antibiotic treatment is not
recommended for otherwise healthy
individuals with ABU because its
use promotes antimicrobial
resistance and other adverse effects,
including the possibility of an
increased risk of symptomatic
UTI.59–62 ABU is frequently
observed in children with
neurogenic bladder, particularly if
the patient is on clean intermittent
catheterization or has a history of
bladder augmentation.63
• Sterile pyuria: Sterile pyuria may
occur in association with infections
such as partially treated UTI,
appendicitis, tuberculosis, or
fungal, viral, or parasitic infections.
It can also occur with immunologic
conditions, such as acute
glomerulonephritis, systemic lupus
erythematosus, and Kawasaki
disease, or with a foreign body,
kidney stones, interstitial nephritis,
analgesic nephropathy, and
papillary necrosis.64,65
Differentiation of APN from cystitis
can be difficult particularly in
preverbal children, and in the febrile
infant, the distinction might be
considered largely academic because
treatment will be similar. Because
most cases of APN are due to
ascending infection, many patients
have both upper- and lower-tract
symptoms, further blurring the
distinction between cystitis and APN.
However, an effort should be made to
localize the infection (because both
the acute management and
subsequent workup of cystitis and
pyelonephritis may differ, particularly
in older children) and to identify the
causative organism (because patients
with viral or chemical cystitis do not
need conventional antibiotic therapy).
Furthermore, unlike APN that needs
second- or third-generation
cephalosporin for at least 1 week,
uncomplicated (nonfebrile) bacterial
cystitis generally responds well to the
short duration (3–5 days) of first-
generation cephalosporin,
trimethoprim-sulfamethoxazole, or
nitrofurantoin.66–69 The utility of
currently available screening tests
(C-reactive protein, procalcitonin, and
erythrocyte sedimentation rate) is
limited. The evidence suggests that an
increased serum C-reactive protein or
procalcitonin level is suggestive of
APN.20 The erythrocyte
sedimentation rate does not appear
useful in diagnosing APN. Some other
features that may be helpful in
differentiating cystitis from APN are
shown in Table 3.66–69
COMPLICATIONS OF UTI
Acute complications of UTI are
similar to those associated with any
febrile illness in a young child. These
include dehydration, electrolyte
abnormalities, and febrile seizures.
Renal complications of APN are
uncommon in otherwise healthy
children but may include renal
abscess or complete occlusion of
a preexisting, partial ureteropelvic
junction obstruction. Acute kidney
TABLE 3 Features That May Be Helpful in Differentiating Cystitis From APN
Characteristic APN
Age distribution More common in younger
children
Fever130 .38°C
Recent viral NA
illness131
Systemic symptoms Common
Local symptoms Flank pain and/or tenderness
Causative agent Bacterial (E coli is the
commonest)
Urinary findings
Gross hematuria Uncommon
Urine culture for Positive
bacteria
RBUS Normal or may reveal edema
and hyperemia of kidney
Renal complication Renal scarring
NA, not applicable.
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PEDIATRICS Volume 147, number 2, February 2021
injury may occur because of
dehydration or an administration of
a nonsteroidal anti-inflammatory
drug, such as ibuprofen. Nonsteroidal
anti-inflammatory drugs may also
diminish renal function by causing
papillary necrosis or interstitial
nephritis. The latter can also be
caused by the antibiotic that is being
used for UTI treatment. Urosepsis
may occur, particularly with Gram-
negative infections.
The most consequential long-term
complication of APN is renal scarring.
The reported prevalence of renal
scarring after febrile UTI is ∼15%39
and ranges from 3% after the first
UTI to 29% after .3 febrile UTIs.36,70
In the Randomized Intervention for
Children with Vesicoureteral Reflux
(RIVUR) trial, only ∼7% of children
developed new scarring during the
study period, and this was primarily
among children with grade 4 VUR.29
In most children, renal scarring may
not be clinically significant,71–73 but it
may cause hypertension and
proteinuria and a progressive decline
in renal function in those with
bilateral significant scarring.74
Delayed initiation of antibiotic
treatment is associated with
increased risk of scarring, with the
odds of new renal scarring 74%
Uncomplicated Cystitis
Typically in children aged .2 y
Afebrile or low-grade fever #38°C
Viral cystitis
Uncommon
Dysuria, urgency, frequency, urinary
incontinence, suprapubic pain, and/or
hematuria
Bacterial (E coli is the commonest), viral,
fungal, and chemical
May have fresh blood and clots131,132
Negative results in viral, fungal, and chemical
cystitis
Normal or may reveal thickened urinary
bladder wall, debris in the bladder
None
lower among children whose
treatment started within 24 hours of
onset of fever, compared with those
whose treatment started after
72 hours of fever.32
RENAL IMAGING AFTER UTI
Renal imaging after UTI is driven
primarily by a need to rule out an
underlying renal or urinary tract
anomaly or the assessment of renal
injury.
Renal Bladder Ultrasound
The purpose of renal bladder
ultrasound (RBUS) is to evaluate for
urinary tract anomalies, including
obstruction, renal structural
anomalies, nephrolithiasis or
calcification, or an abdominal mass.
RBUS is a less sensitive imaging
modality for the diagnosis of VUR,75
and normal RBUS does not rule out
high-grade VUR. Particular findings
on RBUS that may indicate a higher
probability of VUR include ureteral
dilation, renal parenchymal changes,
and bladder abnormalities. RBUS
cannot be used to accurately diagnose
patients with APN or renal
scarring.76–78 The 2011 AAP
guidelines recommend RBUS be
performed in all infants (2–24
months) with febrile UTI.34 Older
children with recurrent UTIs may also
benefit from an RBUS. The RBUS can
be deferred until after resolution of
the UTI but should be considered
during the acute episode if the illness
seems unusually severe or if high
fevers persist beyond 48 to 72 hours
of treatment34; such atypical course
suggests complications, such as renal
abscess or occult obstruction, that are
well-seen on RBUS. A deferred RBUS
permits more accurate interpretation
of the anatomy, without potential for
false-positive findings associated with
tissue edema or endotoxin-induced
dilation.
Voiding Cystourethrogram
In the last decade, the practice
patterns have dramatically shifted,
5
with far fewer patients undergoing
voiding cystourethrogram (VCUG)
after an initial UTI.79,80 This trend is
consistent with many published
guidelines, including those by the
AAP.34,81,82 Part of the reason for
this is that less than one-third of
children with their first UTI have
VUR, and of these, fewer than 10%
have grade 4 to 5 VUR.7,83 A VCUG
should be considered after first UTI
in children with abnormal RBUS,
atypical causative pathogen,
complex clinical course, or known
renal scarring.34,81,82,84 Patients
with a family history of VUR or
CAKUT can also be considered for
VCUG after first febrile UTI. The
interobserver variability in VUR
grading must be kept in mind while
making clinical decisions.85
DMSA Renal Scan
DMSA scan is the current gold
standard for assessment of renal
parenchymal injury in a child with
a history of febrile UTI. It is more
sensitive for renal scarring than
RBUS, which misses a substantial
proportion of such cases.40,86,87
However, most children with first
febrile UTI do not need a DMSA renal
scan.34 It may be considered in
children with recurrent febrile UTIs
or renal parenchymal abnormalities
on RBUS. Demonstration of renal
scarring increases the risk for further
renal deterioration.88 Findings of
renal scarring may influence surgical
decision-making in patients with
surgically correctable conditions (eg,
VUR). Cortical defects on DMSA scan
performed during or shortly after
APN may be due to preexisting
lesions (either acquired or
congenital) or to the acute
inflammatory reaction associated
with APN. A delayed DMSA scan at 4
to 6 months allows the acute
inflammatory reaction to subside, at
which point any persistent cortical
defects can be assumed to represent
permanent renal scarring, although in
the absence of baseline (pre-APN)
scans, it may still be difficult to
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6 MATTOO et al
differentiate acquired from congenital
lesions.89
ANTIBIOTIC TREATMENT
The choice of an antimicrobial for
empirical therapy should be guided
by the local, resistant patterns of
uropathogens. However, in general in
young febrile children, in whom the
chance of renal involvement is high, it
is prudent to choose an antimicrobial
to which only a small proportion of
organisms are resistant. At the time of
writing, the vast majority of
uropathogens are sensitive to third-
generation cephalosporins.90 In
children who are not febrile, it would
be more reasonable to use a first-
generation cephalosporin,
trimethoprim-sulfamethoxazole, or
nitrofurantoin.90 Most uropathogens
are resistant to amoxicillin, and its
use should therefore be avoided.
Many studies have revealed that
children aged .2 months can be
safely managed with oral antibiotics;
thus, hospital admission for
treatment should be avoided unless
the child is unable to tolerate oral
antimicrobial therapy. Fever resolves
in 68% of children in the first
24 hours and in 92% by 72 hours.91 If
fever persists beyond 72 hours, the
clinician should reevaluate the
diagnosis and decide whether an
RBUS is emergently needed to rule
out renal abscess. Antibiotic
treatment should be started within
48 hours of fever onset because
delayed treatment increases the risk
of renal scarring.30–32 Oral antibiotic
therapy for 7 to 10 days is adequate
for uncomplicated febrile UTI
presumed to be APN that responds
well to the treatment. In a recent
study, researchers reported that in
infants aged ,60 days with
bacteremic UTI, #7 days of
parenteral antibiotic therapy may be
as safe and effective as conventional,
longer-duration treatment.68 In
another recent study in children,
researchers reported that 6 to 9 days
of antibiotic treatment is as effective
for treating APN as a longer duration
of $10 days.69 Routine follow-up
urinalysis and culture (so-called
proof-of-cure tests) after the
resolution of UTI symptoms are not
necessary unless clinically
indicated.92,93
ROLE OF ANTIMICROBIAL PROPHYLAXIS
The effectiveness of antimicrobial
prophylaxis in the prevention of UTI
recurrence has been studied
extensively. The RIVUR trial revealed
that trimethoprim-sulfamethoxazole
prophylaxis reduced the risk of UTI
recurrence by 50%. Similar results
were reported by another placebo-
controlled, double-blind (PRIVENT
study) trial.94 Combined results of the
RIVUR and the Careful Urinary Tract
Infection Evaluation (CUTIE) studies
revealed that toilet-trained children
with VUR and BBD exhibit the
greatest benefit from antimicrobial
prophylaxis.95 However, many other
randomized studies have revealed
either a sex-based96 or no97–101
beneficial effect with prophylaxis. In
systematic reviews and meta-
analyses, researchers have also
reported mixed results, with some
concluding that prophylaxis is
effective102,103 and others reporting
that prophylaxis offers no or little
advantage for the prevention of UTI
recurrence.104,105 These variations in
results have been attributed to
significant differences in study
designs, including patient inclusion
and exclusion criteria.106 No study
has demonstrated any beneficial
effect of antimicrobial prophylaxis for
the prevention of renal scarring,
although one must add that none of
these studies were powered to
evaluate renal scarring as a primary
study end point, and even a recent
meta-analysis was likely
underpowered to reveal an effect.107
Antibiotic resistance is a major risk of
long-term prophylaxis108 and, hence,
should be used selectively.106,109,110
In cases of febrile UTI and VUR, the
American Urological Association
recommends continuous antibiotic
prophylaxis in children aged
,1 year and a selective approach in
older children based on patient age,
severity of VUR, recurrence of UTI,
presence of BBD, and renal cortical
anomalies.111 The European
Association of Urology, European
Society of Pediatric Urology, and
Swedish and Italian Society of
Pediatric Nephrology also
recommend a more selective
approach based on a combination of
patient age, severity of VUR, and
renal scarring.112–114 Other factors
that should be considered before
initiating long-term antimicrobial
prophylaxis include the status of
toilet training, risk of antibiotic
resistance, anticipated compliance
with daily medication
administration, parental choice, and
the medication expense. In all
recommendations, younger age is
a particular consideration for
prophylaxis because of a nonspecific
clinical presentation for UTI, the
difficulty in getting urine specimens,
the higher possibility of a need for
hospitalization for intravenous
antibiotic administration and
hydration, an increased risk of
septicemia, and family disruption
and parental anxiety. In some cases,
a preemptive antimicrobial
prophylaxis may be necessary to
lower the risk of first UTI, such as in
those with high-grade VUR
diagnosed during workup for
antenatal hydronephrosis. The
duration of prophylaxis depends on
multiple factors and may range from
a few days until a VCUG can be
obtained in those recently
diagnosed with UTI to a few years
for children with VUR on medical
management.
Secondary analysis of the RIVUR study
has revealed that the patients who
took trimethoprim-sulfamethoxazole
,70% of the time were 2.5 times
more likely (95% confidence interval
1.1–5.6) to have a recurrent UTI and
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PEDIATRICS Volume 147, number 2, February 2021
were at highest risk for renal scarring
(odds ratio 24.2, 95% confidence
interval 3.0–197), as compared to
most adherent patients.115 It also
revealed that the long-term
prophylaxis with trimethoprim-
sulfamethoxazole was not associated
with an increased risk of skin and soft-
tissue infections, pharyngitis or
sinopulmonary infections,116 or
excessive weight gain.117 In another
study, researchers reported that
routine monitoring of blood chemistry,
renal function, or complete blood cell
count were not necessary in children
receiving long-term trimethoprim-
sulfamethoxazole prophylaxis.118
Regarding the cost-effectiveness of
antibiotic prophylaxis, one study
revealed that the prophylaxis was
associated with marginally higher
costs, as compared with placebo,119
whereas researchers in another study
reported that the prophylaxis was
more cost-effective than observation
in children with high-grade (grade 4)
but not low-grade VUR; this finding
should be considered in light of the
fact that the large majority of children
with VUR do not have high-grade
disease.120
Antibiotic resistance of pathogens
causing UTI at any age is a growing
concern internationally.121–125 As
such, there is a need for a judicious
use of antibiotics for the prevention
and the treatment of UTIs. Some of
the measures that could help
reduce the risk of antibiotic
resistance in children with UTIs are
as follows126 :
• Collection of uncontaminated urine
specimen for diagnosis so that
patients do not receive an antibiotic
for a false-positive urine culture
result;
• Initiation of empirical antibiotic
therapy only after collecting an
uncontaminated urine specimen to
help with the selection of a right
antibiotic for continued treatment
or its discontinuation, depending
on the urine culture results and the
patient’s clinical status;
• Avoiding or deferring the use of
antibiotic in a patient suspected of
having viral or chemical cystitis;
• Not using a routine, long-term
antimicrobial prophylaxis in low-
risk patients; and
• Not treating ABU with antibiotics.
SURGICAL INTERVENTION FOR VUR
Few patients diagnosed with VUR after
UTI need surgical correction. It is
usually reserved for patients with high-
grade VUR, recurrent UTI despite
antibiotic prophylaxis, and
noncompliance with or intolerance of
prophylactic antibiotics and for the
worsening of renal scars.127 Open
ureteral reimplantation remains the
mainstay of surgical correction for
VUR, although endoscopic treatment is
also widely used, particularly for
lower-grade VUR. Laparoscopic
reimplantation techniques (with or
without robotic assistance) have
increased in recent years, but use
remains limited to specific centers.
Endoscopic treatment involves
subureteral or intraureteral injection of
a bulking agent (most commonly
dextranomer and hyaluronic acid
[Deflux]). The decision for timing and
the type of intervention is based on the
age of the patient, status of the kidneys,
grade of VUR, and parental wishes.6
PREVENTION OF RECURRENT UTI
Recurrent UTI can be prevented by
preventing constipation and
avoidance of urine withholding
behavior in toilet-trained children.
Although increased oral fluid helps
flush bacteria from the bladder,
prompts frequent urination, and
alleviates constipation, there is
limited evidence that it is effective in
preventing UTIs.128 In uncircumcised
boys, gentle, daily retraction and
cleaning should be performed; in
boys with phimosis, topical
corticosteroid ointment or
circumcision may be necessary to
prevent UTI recurrence. There is no
evidence in children to recommend
7
cranberry juice for the prevention of
UTIs. In a systematic review of studies
in adults, researchers concluded that
given the evidence, cranberry juice
cannot currently be recommended for
the prevention of UTIs.129
CONCLUSIONS
A good clinical assessment
supplemented by laboratory results on
an uncontaminated urine specimen is
essential for the accurate diagnosis of
UTI in children. Renal ultrasound
examination is recommended after first
UTI in younger children and recurrent
UTI in older children. Most children
with first febrile UTI do not need
a VCUG, but an early VCUG is
appropriate in some patients. Prompt
antibiotic treatment reduces morbidity
and the risk of renal scarring. Oral
antibiotic administration for 7 to
10 days is sufficient to eradicate
infection in those with a good clinical
response. Surveillance urinalysis and
culture after UTI are not necessary
unless clinically indicated. A selective
use of antimicrobial prophylaxis is
considered in patients with recurrent
UTI and those with a high risk of renal
scarring. Careful use of antibiotics is
essential for the prevention of drug
resistance of pathogens causing UTIs.
ABBREVIATIONS
AAP: American Academy of
Pediatrics
ABU: asymptomatic bacteriuria
APN: acute pyelonephritis
BBD: bladder-bowel dysfunction
CAKUT: congenital anomalies of
kidneys and the urinary
tract
CFU: colony-forming unit
DMSA: dimercaptosuccinic acid
RBUS: renal bladder ultrasound
RIVUR: Randomized Intervention
for Children with Vesi-
coureteral Reflux
UTI: urinary tract infection
VCUG: voiding cystourethrogram
VUR: vesicoureteral reflux
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8 MATTOO et al
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MATTOO et al
 Contemporary Management of Urinary Tract Infection in Children
Tej K. Mattoo, Nader Shaikh and Caleb P. Nelson
Pediatrics 2021;147;
DOI: 10.1542/peds.2020-012138 originally published online January 21, 2021;

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 Contemporary Management of Urinary Tract Infection in Children
Tej K. Mattoo, Nader Shaikh and Caleb P. Nelson
Pediatrics 2021;147;
DOI: 10.1542/peds.2020-012138 originally published online January 21, 2021;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/147/2/e2020012138

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