Current Pediatrics Reports

https://doi.org/10.1007/s40124-018-0181-8

RENAL (D NOONE, SECTION EDITOR)

Urinary Tract Infection in Children

Nicholas G. Larkins 1,2 & Ian K. Hewitt 1,2

# Springer Science+Business Media, LLC, part of Springer Nature 2018

Abstract
Purpose of Review Urinary tract infections (UTI) are common among children. In the past 20 years, a number of key trials have
substantially changed practice, in addition to clarifying the natural history of children managed expectantly. It is now clear that
among children with normal kidneys at presentation, chronic kidney disease and hypertension are rare. Improved antenatal
ultrasound now detects most significant abnormalities of the kidney and urinary tract, particularly severe hypodysplasia, which
is often associated with high-grade vesico-ureteric reflux (VUR). This review aims to summarize the evidence-based treatment of
UTI in children.
Recent Findings There is no difference in symptomatic, microbiologic, or renal outcomes between intravenous and oral antibi-
otics in treating acute, febrile infection. Long-term antibiotic prophylaxis results in a statistically but not clinically significant
reduction in recurrence among young children, with or without VUR. Trials to-date have failed to demonstrate that the surgical
correction of VUR confers any additional benefit, which may be because the natural history of VUR is to resolution with time
and/or that other factors are more important determinants of outcome.
Summary A more conservative approach to the management of UTI is warranted for most children. Antibiotic prophylaxis,
voiding cystourethrography, and surgery for VUR are not indicated following an initial or infrequent UTI. These measures may
have a role in selected subgroups of children at high risk of kidney disease, but this remains a hypothesis pending the results of
ongoing trials.

Keywords Child . Urinary tract infections . Vesico-ureteral reflux . Antibiotic prophylaxis . Pyelonephritis

Introduction sequalae in an immunocompetent host, and will not be further

Urinary tract infection (UTI) is a common childhood infec-
tion, occurring in around 8% of females and 2% of males
before 7 years of age [1]. Most UTI are bacterial, caused by
ascending gastrointestinal commensal organisms, the most
common of which is Escherichia coli (E. coli). Viral and fun-
gal infections can also cause UTI, the most common example
being adenoviral cystitis; but these rarely result in significant
discussed here.
Pyelonephritis was thought to predispose to chronic kidney
disease in children and was routinely treated with intravenous
(IV) antibiotics followed by extensive investigation, antibiotic
prophylaxis, and/or surgery where vesico-ureteric (VUR) was
detected. However, a series of well-conducted randomized
controlled trials (RCT) have led to substantial changes in our
understanding and our practices around UTI in children [2, 3].

This article is part of the Topical Collection on Renal

Risk Factors for UTI
* Ian K. Hewitt
ian.hewitt@health.wa.gov.au Both host and pathogen factors contribute to the development
of UTI. Urine flow is an important defense mechanism, acting
Nicholas G. Larkins
nicholas.larkins@health.wa.gov.au
to displace ascending bacteria. Urinary stasis, such as in chil-
dren with bladder abnormalities or obstruction, predisposes to
1
Department of Nephrology, Perth Children’s Hospital, 15 Hospital infection. Uropathogenic E. coli, the predominate organism
Ave, Nedlands, WA 6009, Australia causing UTI, possess multiple virulence factors including fim-
2
School of Paediatrics and Child Health, University of Western briae that facilitate adherence to the uroepithelium, toll-like
Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia receptor disruptors to inhibit the immune response, and

biofilm components that ensure long-term survival within the
renal tract [4–6]. Bacteria that lack fimbriae infrequently cause
UTI in children with a normal urinary tract [7].
During the first 6 months of life, UTIs are more common in
males, thereafter, they occur much more frequently among
females, driven primarily by non-febrile infections [8, 9•].
There is some evidence to suggest that UTI are less common
among circumcised males; although the data are mostly ob-
servational, the estimated effect size is substantial (odds ratio
0.13; 95% confidence interval [CI], 0.08 to 0.20) [10, 11].
Children with bladder abnormalities, such as a neurogenic
bladder are at increased risk of UTI [12]. These patients re-
quire specialist care, but a more commonly encountered form
of bladder disturbance is lower urinary tract dysfunction
(LUTD), which is a delay in the development of normal blad-
der filling and emptying patterns that develop during early
childhood [13, 14]. LUTD is detected in around 30 to 50%
of toilet-trained children presenting with UTI [15, 16].
Children with LUTD may be chronically colonized, only in-
termittently manifesting UTI symptoms [1]. Synonymous
terms include dysfunctional voiding, dysfunctional elimina-
tion syndrome, detrusor instability, and bowel and bladder
dysfunction; highlighting the inter-related nature of the ner-
vous supply to this region [13]. LUTD may manifest as ur-
gency, fidgeting, avoidance of toileting (holding on), and/or
diurnal enuresis [14].
Recurrent UTI and Renal Scarring
Of children < 2 years old, presenting with a UTI, nearly 60%
will have evidence of pyelonephritis on acute
dimercaptosuccinic acid scan (DMSA); and 15% overall will
develop a renal scar [17, 18]. Rational treatment decisions
require information on the risk of recurrent UTI, formation
of new renal scars, clinically relevant sequalae, and the effi-
cacy of any proposed treatment.
Among children in the Randomized Intervention for
Children with Vesicoureteral Reflux (RIVUR) and Careful
Urinary Tract Infection Evaluation (CUTIE) cohorts, < 6 years
of age, toilet trained, not on prophylaxis, presenting with a
first or second UTI, the risk of recurrent UTI over the follow-
ing 2 years of follow-up was 32% [19]. This risk reduces over
time and is greatest in the first 3 to 6 months following the
index infection [20•]. Hence, most children will not have an-
other UTI after their first, or at least will not develop frequent
infections.
Recurrent UTI are more common in children with renal
scarring or an abnormal renal tract ultrasound on presentation
[15, 21]. LUTD is an important risk factor for recurrence,
which may be more significant when present in combination
with vesico-ureteric reflux (VUR) [15, 19]. In isolation, VUR
is a poor predictor of recurrent UTI [15, 19, 20•].
Curr Pediatr Rep
The risk of developing a new scar following childhood UTI
can be stratified according to presenting features. Several
teams have analyzed this question using different data and
approaches, but one excellent example is an individual-
patient meta-analysis that included 1280 children from the
RIVUR, the prevention of recurrent urinary tract infection in
Children with Vesicoureteric Reflux and Normal Renal Tracts
(PRIVENT), and Italian Renal Infection Study-1 (IRIS-1) tri-
als [9•, 18, 20•, 22•]. While the presence of grade 4 or 5 VUR
the was associated with an increased risk of scarring, only
4.1% patient had either grade of reflux [18]. Of multiple
models tested, one including temperature, ultrasonographic
findings (normal versus abnormal), and the presence of an
organism other than E. coli identified patients at risk of scar-
ring almost as well as more complex models that included
blood tests and/or VCUG [18]. Children with ≥ 2 of these risk
factors were at increased risk; whereas children with 1 or none
of these factors developed scarring in 14.3 and 6.2% of cases
respectively (baseline risk 15.6%), and encompassed most of
the cohort (78.3% of children). LUTD is increasingly recog-
nized as an important predictor of future renal scarring, prob-
ably as a result of recurrent UTI. The OR for scarring among
children without LUTD in the RIVUR and CUTIE cohorts
was 0.32 (95% CI, 0.13 to 0.74) [23].
One of the key changes in our approach to UTI has come
from the realization that most children who go on to develop
renal impairment have abnormal renal findings at presenta-
tion, particularly renal (hypo)dysplasia and structural abnor-
malities, and that the risk among children with normal kidneys
in the presence or absence of VUR is low [24]. Given the
difficulty in differentiating scarring and dysplasia on cross-
sectional studies, it is likely that many people previously di-
agnosed with kidney disease due to VUR actually had renal
dysplasia. This would explain why despite the introduction of
more active treatment for UTI and VUR during the period of
1970 to 2000, there was little appreciable change in the inci-
dence of end-stage kidney disease (ESKD) labeled as reflux
nephropathy [25]. The incidence of ESKD attributed to reflux
nephropathy has fallen markedly in recent years, likely the
result of increasingly accurate antenatal ultrasounds detecting
more cases of dysplasia antenatally that may previously have
been labeled as reflux nephropathy if detected following a
UTI [26–29]. The newer term, congenital abnormalities of
the kidney and urinary tract (CAKUT), is more reflective of
the underlying etiology in most cases [30]. Whereby, it is
thought that the most common sequence of events is abnormal
ureteric budding failing to induce normal kidney development
within the metanephric mesenchyme, which would explain
the observed association between renal dysplasia and VUR.
While the rate of confirmed mutation in children with
CAKUT remains < 20%, this number is increasing, and con-
sistent with a heterogenous, genetically complex group of
disorders [31].
Curr Pediatr Rep
Diagnosis
It is important to avoid treating asymptomatic bacteriuria, as
there is no evidence that this is a sinister condition. Two large,
prospective cohort studies have been conducted, demonstrat-
ing a prevalence of covert bacteriuria between 1 and 2.5% of
children [32–34]. Neither study, one of which randomized 5-
to 12-year-old schoolgirls to treatment or not, indicated that
treatment of covert bacteriuria improves renal outcomes or
averts a significant number of episodes of pyelonephritis.
The first step in correctly establishing the diagnosis is the
collection of an uncontaminated sample. Bag urine collections
are useful to rule out infection only [35, 36]. Clean-catch
samples and catheter samples may also be contaminated,
and the growth of a single, potentially causative organism at
a concentration of ≥ 107 (clean-catch) or ≥ 108 (catheter) is
most consistent with the diagnosis [37]. Samples collected
via supra-pubic aspiration are less frequently contaminated,
and any growth on such a sample is considered consistent with
infection. Systemically unwell infants require a catheter sam-
ple or supra-pubic aspiration to avoid delay in antibiotic ad-
ministration. Otherwise, many centers will initially attempt a
clean-catch sample, as a less invasive method. Gentle stimu-
lation has been proposed to improve the rapidity and proba-
bility of a successful clean-catch sample, a theory supported
by the results of a recent RCT using cold-soaked gaze in 344,
1- to 12-month children (31% versus 12% voided within
5 min) [38].
Pyuria is present in nearly all symptomatic UTI. A simple
threshold of ≥ 1+ leukocyte esterase or positive nitrites on
urinalysis may have a sensitivity up to 95% and specificity
of 98% [39]. Similar test performance has been described
among younger children, and a negative urinalysis almost
excludes urosepsis among children < 60 days [40, 41].
However, study results are heterogenous and meta-analysis
summary estimates less promising, with a pooled sensitivity
of 88% and specificity of 79% for leukocyte esterase or nitrite
positivity [42]. Where available, microscopy with gram stain
may still be the most accurate rapid diagnostic test [42]. The
use of other urine biomarkers to reflect tubular injury (e.g.,
NGAL) and inflammation (e.g., IL-8) has been proposed to
predict UTI in children [43]. These newer biomarkers remain
unavailable in clinic practice, but represent a promising line of
inquiry.
An important problem when considering diagnostic test
accuracy studies for UTI, is that of a faulty gold standard,
given asymptomatic bacteriuria is not uncommon [44].
Hence, there is some uncertainty around this evidence-base,
and results need to be interpreted within the clinical context.
Our certainty of UTI increase as pyuria or bacteriuria in-
creases, but in a patient with classic clinical findings, a lower
white cell or bacterial count do not always exclude UTI, par-
ticularly among younger children [45].
Antibiotic Regimens for Acute Infection
Previous dogma was to treat children with febrile UTI for
2 weeks with intravenous (IV) antibiotics. However, a series
of trials, testing progressively shorter IV therapy followed by
oral treatment found no difference in outcomes [46–48].
Subsequent trials compared 3 days of initial IV therapy with
exclusively oral treatment, the first included 306 children from
1- to 24-month old; [49] the second, 502 children from
1 month to 7 years old [9•]. Both showed no difference in
outcomes including time to resolution of fever, microbiologi-
cal resolution of infection, and subsequent scar formation.
These studies confirmed that beyond 1 month of age, children
with a febrile UTI, of whom ~ 60% have pyelonephritis, who
are otherwise well and tolerating fluids, can be treated with
oral antibiotics in an outpatient setting [50]. Concern about the
rapidity with which young infants may deteriorate has led to
some employing a slightly higher age threshold (for example,
3 months) for treating pyelonephritis with oral antibiotics only
[51]. Children unable to tolerate oral antibiotics require IV
treatment initially, but can be transitioned to oral therapy as
soon as tolerated. One approach is to give a long-acting IV
antibiotic such as ceftriaxone or gentamicin initially, with ear-
ly review and transition to oral antibiotics in patients, where
there is concern whether a child will tolerate oral antibiotics
initially; acknowledging that this does not improve outcomes
for febrile UTI overall [52].
The antibiotic(s) of choice varies between countries, in part
based on availability. As a general principle, gram-negative
cover is essential, often achieved using gentamicin when IV
therapy is required. The renal excretion of gentamicin is ad-
vantageous in this setting, because levels achieved at the site
of infection (i.e., renal parenchyma) are many fold higher than
serum levels [53]. Most pediatricians will add a penicillin,
such as amoxicillin, to cover enterococci, which comprise
around 3% of infections in children with normal urinary tracts
[20•]. Where patients are treated solely with oral antibiotics,
empiric selection will depend upon the sensitivity profile
of common organisms, mainly E.coli, in that community,
which varies by region and time according to prescribing prac-
tices [54, 55]. In many places, a high proportion of E. coli
are resistant to amoxicillin; common choices include
cotrimoxazole, cephalexin, amoxicillin-clavulanic acid, and
cefixime [55, 56].
In-lieu of trial data on the duration of treatment for pyelo-
nephritis in children, a standard 10- to 14-day course of ther-
apy appears appropriate. There are observational, and limited
trial data to support a 3- to 5-day course in children with
cystitis [57–59]. Shorter (or symptomatic-only) courses for
adults with cystitis have been investigated [60, 61].
However, we would not recommend this approach for most
children, given single dose treatment regimens have been
trialed and are less effective than longer courses [57].

Management of Recurrent UTI
Prophylactic Antibiotics
The use of prophylactic antibiotics following initial UTI in
young children, with or without VUR, is another area of prac-
tice that has changed substantially in response to RCT data.
Four studies published between 2006 and 2008 showed no
statistical benefit of antibiotic prophylaxis in preventing
UTIs, pyelonephritis or subsequent renal scarring, but mostly
enrolled patients with absent or lesser grades of VUR and
were not placebo controlled [62–65]. Subsequently, two
well-designed, placebo-controlled trials have demonstrated
that prophylaxis produces a statistically, but not clinically sig-
nificant, reduction in UTI recurrence; requiring 14 to 16 pa-
tient years of antibiotic administration to prevent one UTI, and
22 patient years of treatment to prevent one febrile UTI [22•,
66]. Neither of these trials demonstrated any interaction be-
tween baseline characteristics, such as VUR, and the effect
size associated with treatment. A further trial that has attracted
much attention is the Swedish reflux study [67]. This study
performed a three-way allocation of children with VUR
grades 3 to 4, to antibiotic prophylaxis, endoscopic correction
of the reflux, or surveillance. Subgroup analysis of the 43 girls
on prophylaxis with the 42 girls with no treatment under sur-
veillance demonstrated a benefit of treatment on recurrent
infections and scarring. It should be cautioned that the num-
bers were small and have not been supported by subgroup
analysis of the 380 girls with VUR grades 3 to 4 randomized
in the RIVUR study. While no individual trial has been
powered to detect a difference in scarring, meta-analysis of
results (7 studies, 1427 children) thus far suggests that a clin-
ically significant difference is unlikely [68].
Any benefit of prophylaxis might be in the early months of
treatment. This was true for the PRIVENT study where the
greatest benefit was seen during the first 6 months of therapy
[20•]. This may reflect a higher event rate in the first months
after an initial infection or increasing antibiotic resistance with
prolonged treatment. Thus, for children who have a series of
UTIs in succession prophylactic antibiotics may still have a
role, initially prescribed as a 3- to 6-month course. As a guide,
the Italian Society of Pediatric Nephrology recommends pro-
phylaxis for children who experience ≥ 3 infections in a 12-
month period [69].
Non-antibiotic agents have been trialed for prophylaxis
of recurrent UTI. Cranberry products have been the most
extensively investigated. Initial trial results were positive,
but the effect size observed in larger RCTs has been sub-
stantially smaller [70, 71]. The results of systematic re-
views are conflicting, but the most recent Cochrane analy-
sis suggests that there is insufficient evidence to recom-
mend cranberries for UTI, and found no evidence of a sub-
group effect among children [72, 73]. More recently,
Curr Pediatr Rep
probiotics have been the focus of some research, but it re-
mains unclear whether they offer benefit over placebo
[74, 75].
Surgery for VUR
Another treatment option for children with UTI and VUR is
surgical intervention, either by endoscopic injection of
bulking agents or by ureteric re-implantation. Both methods
are effective in improving VUR, but whether they result in a
clinically meaningful improvement in patient outcomes is
unclear [28]. As antibiotic prophylaxis is not without ad-
verse effects, neither is surgical intervention, with up to 7%
of patients developing obstruction following ureteric re-
implantation [76]. Several trials have compared surgery with
antibiotic prophylaxis, the largest being the International
Reflux Study in Children [77, 78]. The IRSC demonstrated
an 11% risk reduction in febrile, but not symptomatic, UTI
over 5 years of follow-up with surgery and antibiotic pro-
phylaxis compared to antibiotic prophylaxis alone. In the
Swedish Reflux Trial, there was no difference between the
endoscopic correction and antibiotic prophylaxis arms, al-
though precision was limited by the small sample size [79].
Neither the Swedish Reflux Trial nor the IRSC found that
surgical intervention improved renal outcomes, including
scarring, renal function, or blood pressure [78, 80]. Despite
a lack of trial data, strong observational evidence supporting
a lower risk of UTI recurrence among circumcised boys has
led to circumcision being offered as an initial approach by
some, when surgical intervention is being considered
[10, 11].
While prophylactic antibiotics and/or surgery appear to
provide a small risk reduction for UTI recurrence among chil-
dren with VUR, it is worth considering the natural history of
this condition. Among children enrolled in RIVUR, VUR
resolved in 50.9% and 23.4% demonstrated an improvement
in VUR grade over the 2 years of follow-up [22•]. Data were
similar for Swedish Reflux Trial participants, of whom 44% of
children with dilating reflux were downgraded to non-dilating
reflux following 2 years of observation [81]. This trend to
resolution, even with high-grade VUR, might explain why
surgical intervention is associated with a smaller effect size
than initially hypothesized.
Management of LUTD
As a common cause of recurrent infections and predictor of
new renal scarring, a history of LUTD needs to be sought and
directed management provided where appropriate. Advice
about simple measures such as timed voiding, good voiding
habits, fluid intake, positive re-enforcement, and pelvic floor
exercises is successful in many cases [82, 83]. The link be-
tween bowel and bladder dysfunction means that constipation
Curr Pediatr Rep

and bowel habit needs to be managed simultaneously with
LUTD [13]. For children who are not improving, multidisci-
plinary care, including additional measures such as biofeed-
back, may be beneficial [13]. The use of validated question-
naires aid in the detection of LUTD and monitoring clinical
progress [84]. These can be self-administered in most cases,
prior to clinic, and thus easily incorporated into day-to-day
practice [14].
Imaging
One of the most controversial aspects of UTI management is
how and when to investigate children for underlying urinary
tract disorders, including VUR. Imaging modalities range
from ultrasound, to radio-isotope scans, to VCUG, and formal
cystograms. Additional investigations for LUTD including
urodynamics, real-time bladder ultrasound, and/or
uroflowmetry are also sometimes included.
Renal tract ultrasound is a relatively cheap, non-invasive
test that will identify nearly all children with major structural
abnormalities, such as posterior urethral valves and severe
ureteropelvic junction obstruction, who benefit from early
surgical intervention. However, most such abnormalities
are detected antenatally, and the yield of routine ultrasound
following a first UTI is low, leading some to question the
role of routine ultrasound in all children following UTI [85].
Most guidelines employ an age threshold, below which
all children with UTI receive an ultrasound; although, this
value varies from 6 months to 16 years (Tables 1 and 2)
[69, 86–89].
Most guidelines no longer recommend VCUG for an
initial, uncomplicated UTI in children with a normal ul-
trasound. Even in children < 3 months of age, the propor-
tion with high-grade VUR among this population is ≤ 1%
[90]. When detected, the management of LUTD is more
effective than other measures such as surgical interven-
tion, such that VCUG is now usually reserved for children
with other imaging abnormalities, or in whom conserva-
tive measures have been unsuccessful [13, 91]. Children
with recurrent pyelonephritis and/or progressive renal
scarring, may benefit from VCUG to detect cases of
high-grade VUR following a less favorable clinical course
that may benefit from surgical intervention. Antibiotic
prophylaxis is often given at the time of VCUG to prevent
procedure-related infection [77, 86].
While the role of ultrasound for most young children
following UTI, and a more restricted use of VCUG, is

Table 1 Key randomized trials of antibiotic prophylaxis for prevention of UTI in children

Study Population Intervention Outcomes

Garin 2006 236 children, 3 months to 18 years following a Cotrimoxazole or No difference in rates of recurrent UTI,
febrile UTI with or without VUR grade 1 to 3. Nitrofurantoin pyelonephritis or development of renal
versus observation parenchymal scars.
for 12 months.
Roussey-Kesler 225 children, 1 month to 3 years with VUR Cotrimoxazole versus No difference in recurrent UTI.
2008 grade 1 to 3 following a first febrile UTI. observation for
18 months.
Pennesi 2008 100 children 1 to 30 months with VUR Cotrimoxazole versus No difference in recurrent pyelonephritis
grade 2 to 4 following a first febrile UTI. observation for or scarring.
2 years.
Montini 2008 338 children, 2 months to 7 years following a first Cotrimoxazole versus No difference in incidence of febrile UTIs or
febrile UTI with or without VUR grade 1 to 3. observation for scarring.
12 months.
PRIVENT 2009 576 children, less than 18 years, following one or Cotrimoxazole versus 14 patient-years of antibiotics to prevent one UTI.
more UTIs. placebo for
12 months.
Swedish Reflux 203 children 1 year to < 2 years with VUR grade 3 Cotrimoxazole, Subgroup analysis comparing 42 girls on
Trial 2011 to 4 following one or several UTIs randomized to endoscopic prophylaxis with 43 girls on surveillance showed a
prophylaxis, endoscopic correction or correction, or benefit in preventing UTI recurrence and scarring.
surveillance. 135 children were on prophylaxis or surveillance for No difference found in boys.
surveillance. 2 years.
RIVUR 2014 607 children, 2 to 71 months, following a first or Cotrimoxazole versus 16 patient-years of antibiotics to prevent one UTI
second UTI with VUR grade 1 to 4. placebo for and 22 patient years to prevent one febrile UTI. No
24 months. difference in renal scarring despite 558/607 (92%)
being female and 380/607 (62%) having VUR
grade 3 or 4.

PRIVENT, Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts; RIVUR, Randomized
Intervention for Children with Vesicoureteric Reflux study; UTI, urinary tract infection; VUR, vesicoureteral reflux
 Curr Pediatr Rep

Table 2 Comparison of
guidelines for childhood UTI Country Age range Diagnosis † Treatment * Imaging

USA 2 months SPA or catheter‡ if unwell. Oral or IV treatment Ultrasound all children. Nil
to Other methods of for 7 to 14 days. further unless risk
2 years collection for factors. Consider VCUG
urinalysis/ruling out for recurrent infections.
infection only. Diagnosis
requires pyuria and CFU
50000.
Canada > 2 months SPA, catheter, or clean Oral or IV treatment Ultrasound all < 2 years.
catch. Other methods of for 7 to 10 days. 2 VCUG if abnormal
collection for to 4 days for ultrasound or recurrent
urinalysis/ruling out cystitis. infections in children
infection only. Do not < 2 years old. May use
send negative for culture DMSA instead of VCUG
if urinalysis negative. for females to rule out
CFU thresholds: any high-grade reflux.
growth on SPA, 5 × 104
for catheter, 105 for
mid-stream.
Italy 2 months Only test symptomatic Oral or IV treatment Ultrasound all 2 months to
to children. If unwell by for 7 to 14 days in 3 years old. Further
3 years catheter, if well by clean children investigation of children
catch. CFU thresholds: ≥3 months old. with atypical infections.
105 for catheter and 106
for clean catch
UK < 16 years Clean catch recommended, Oral or IV treatment Ultrasound all < 6-month,
urine collection pads for 7 to 14 days in older if atypical or
should be used next (not children recurrent infections.
cotton-wool or sanitary ≥ 3 months old. DMSA for recurrent or
towel), then catheter or 3 days for cystitis. atypical infection
SPA. Do not send urine < 3 years + VCUG if
for culture in children < 6 months. DMSA for
≥ 3 months if urinalysis recurrent infections in
negative. ≥ 3 years,
Australia <16 years Only treat symptomatic Oral or IV for 7 to Ultrasound all < 3 months
infections. SPA, catheter 10 days in old, if no antenatal
or clean catch sample. > 1-month-old ultrasound in 2nd or 3rd
CFU thresholds: any children. 2 to trimester. VCUG if
growth on SPA, 104–105 4 days for cystitis. recurrent pyelonephritis.
possible and > 105 Delayed DMSA if
diagnostic for catheter, concern about reduced
104–105 possible and kidney function.
> 105 diagnostic for
clean catch.

2011SPA, supra-pubic aspirate; CFU, colony forming units per milliliter; IV, intravenous; VCUG, voiding
cystourethrogram; DMSA, dimercaptosuccinic acid scan.*All guidelines recommend IV therapy initially for
unwell appearing children; † mid-stream urine in toilet trained children; ‡ In-out urinary catheter sample. No
guideline recommends routine prophylaxis after an initial UTI, aside from Italy in children with ≥ grade 3 VUR

now common practice, the perceived role of nuclear med-
icine varies widely. Different nuclear scans provide differ-
ent, but complementary pieces of information. A
technetium-99 m mercaptoacetyltriglycine (Mag-3) scan
can provide information about obstruction, function, and
include an indirect cystourethrogram. Although, the accu-
racy of the later in ruling out VUR, as is its purpose, may
be low [92]. DMSA scanning is the gold standard to
detect renal scarring which appears as a localized cortical
uptake defect, as well as renal hypodysplasia which typi-
cally appears as a universally smaller kidney with reduced
isotope uptake. However, it does not provide information
about urine flow or obstruction.
A normal DMSA, in combination with a normal ultra-
sound, makes high-grade VUR unlikely [85, 93, 94]. This
approach was employed in the 2007 NICE guidelines,
Curr Pediatr Rep
which incorporated delayed DMSA and ultrasound, but
advised against VCUG in most children; breaking from
what had prior-to been considered standard practice [51,
95]. However, this top-down approach, is not without
cost, in terms of radiation, discomfort, expenditure, and
leads to a large number of false positive results [96].
Open Trials
One focus of ongoing research is the investigation of
more conservative approaches among children at in-
creased risk of chronic kidney disease. For example,
the Antibiotic Prophylaxis and Renal Damage in
Congenital Abnormalities of the Kidney and Urinary
Tract trial (PREDICT) is randomizing children, 1 to
4 months old, with high-grade VUR, to prophylactic
antibiotics or placebo prior to any reported UTI. The
study aims to determine if dysplastic kidneys are more
prone to damage as a consequence of pyelonephritis and
whether antibiotic prophylaxis is of benefit in this con-
text. Further research is examining the optimal total
treatment length for acute infection, including an RCT
of 221 children, comparing 7 and 10 days of antibiotic
treatment for febrile UTI [97].
Conclusion
UTI is a common infection in children. While some chil-
dren will develop renal scarring following infection, most-
ly these scars are not clinically significant. Children at
significant risk of chronic renal insufficiency appear to
be those with CAKUT, particularly boys with renal
hypodysplasia. These data, in combination with a modest
treatment effect for either prophylactic antibiotics or sur-
gery, mean most children are now treated conservatively
following an initial UTI. LUTD is an important cause of
recurrent infections and scarring, and when identified
should be the initial focus of management. A small num-
ber of children who go on to develop frequent episodes of
pyelonephritis, may benefit from prophylactic antibiotics,
and/or surgery if VUR is present.
Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflicts of
interest.
Human and Animal Rights and Informed Consent This article does not
contain any studies with human or animal subjects performed by any of
the authors.
References
Papers of particular interest, published recently, have been
highlighted as:
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