JOURNAL OF TROPICAL PEDIATRICS, VOL. 59, NO.

6, 2013

Controversy in Urinary Tract Infection Management in

Children: A Review of New Data and Subsequent
Changes in Guidelines
by Jameela Abdulaziz Kari,1,2 and Kjell Tullus1
1
Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Saudi Arabia

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2
Department of Nephrology, Great Ormond Street Hospital for Children, UK

Correspondence: Jameela A. Kari, Department of Pediatrics,

King Abdulaziz University Hospital, PO Box 80215, Jeddah 21589, Saudi Arabia. Telephone: þ996 55677904. Fax: þ996 (2)
6684603. E-mail <jkari@doctors.org.uk>.

Summary
Controversy and lack of consensus have been encountered in the management of pediatric urinary tract
infection (UTI), including its diagnosis, radiological investigations and the use of antibiotic therapy. In
this review, we discuss the need for radiological investigations and the extent of their use as well as the
need for prophylactic antibiotics in children with UTI and vesicoureteral reflux. Only a small proportion
of children with first UTI and no history of antenatal renal abnormalities have clinically important
malformations. Renal ultrasound should be performed in febrile infants and young children with UTI; a
micturating cystourethrogram should not be performed routinely after the first febrile UTI. Long-term
antibiotics appear to reduce the risk of recurrent symptomatic UTI in susceptible children, although the
clinical benefit is marginal. Current recommendations encourage performing radiological investigations
only in children at risk and discourage routine prophylactic antibiotic use.

Key words: children, radiological investigations, urinary tract infection, vesicoureteral reflux

Introduction detection of VUR would give an opportunity for

Imaging tests have been traditionally performed in
pediatric patients with urinary tract infection (UTI)
with the aim of detecting renal anomalies and vesi-
coureteral reflux (VUR). It was thought that the
Acknowledgements
The authors also thanks clinical research unit at
KAUH for their assistance with the statistics and
writing up this paper.
Funding
This project was funded by the Deanship of Scientific
Research (DSR), King Abdulaziz University, Jeddah
under the grand number (432/003/d) for Pediatric
Nephrology research. The authors therefore
acknowledge with thanks DSR technical and finan-
cial support.
Conflict of Interest: None declared.
physicians to intervene early, either by treating the
VUR surgically or by using prophylactic antibiotics,
to prevent subsequent renal scarring.
Formerly, the American Academy of Pediatrics
(AAP) [1] and the Royal College of Physicians of
London [2] recommended that infants and young
children with first-time UTI should have imaging
tests to evaluate the possibility of VUR. The severity
of VUR was thought to correlate with the risk of
developing permanent renal scarring. It was also
believed that this scarring would cause serious seque-
lae later in life, such as hypertension, pregnancy com-
plications, renal failure and, even, end-stage renal
disease (ESRD). Those recommendations resulted
from earlier studies that showed that renal scarring
was present in 10–25% and VUR was present in 30%
of children with UTI [3–5]. It has, however, recently
become increasingly evident that these previous
approaches led to overdiagnosis and overtreatment
of clinically insignificant VUR.
The new recommendations from the AAP and
the National Institute for Health and Clinical
Excellence (NICE) in the UK state that radiological

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doi:10.1093/tropej/fmt054 Advance Access published on 28 June 2013

investigations should be markedly reduced in chil-
dren with UTI [6, 7].
In the current review, we discuss the new data
about the need for radiological investigations and
the extent of their use as well as the need for prophy-
lactic antibiotics in children with UTI and VUR to
prevent further UTI. We also discuss changes in the
guidelines for radiological investigations and present
NICE and AAP guidelines in detail.
Why Should We Reduce the Radiological
Investigations in Children With UTI?
The aim of investigating children with UTI is to pre-
vent long-term complications that were thought to be
the result of renal scars known to develop as sequelae
to the infection. However, during the past decade,
there have been several important studies that have
questioned this understanding. There is evidence that
renal scars often are congenital or primary, with
in utero renal damage, particularly in boys, where
they are usually associated with dilated reflux [8, 9].
The severity of renal scars seen post UTI and subse-
quent impairment of kidney function has come into
question. We have learnt that most significant renal
anomalies are detected antenatally during the per-
formance of routine ultrasound in the mothers [10].
Therefore, in children with first UTI and history of
normal urinary tract ultrasound antenatally, clinic-
ally important malformations are only found in a
small percentage.
Several recent studies have also questioned the
need to explore the possibility of VUR in all chil-
dren with a single episode of acute pyelonephritis.
There is evidence that early diagnosis and early
treatment are more important than prophylaxis in
preventing renal scars [9]. Fernandez-Menendez
et al. [11] reported that a therapeutic delay time of
48 hours or more was associated with renal scars in
children with UTI. They also observed that children
with abnormal renal scans had longer mean thera-
peutic delay time than those with normal scans
(p < 0.0005). In another study on 20 girls with UTI
and VUR, Coulthard et al. [12] reported that
prompt treatment appeared to prevent scarring in
children with VUR.
We will here review the data that underlie the shift
in policy and also give recommendations on how to
manage a child with febrile UTI.
The Importance of Postinfectious Renal Scars
It is obvious in pediatric nephrology practice that
severe impairment of kidney function in children is
related to dysplastic or scarred kidneys. The import-
ant question is how common that is after a first epi-
sode of febrile UTI. To understand this, one will need
to review population-based epidemiological studies.
Several such studies have been done in the city,
466
J. A. KARI AND K. TULLUS
Gothenburg (500 000 inhabitants). We present data
from this important series of studies.
All children in Gothenburg who had an episode of
UTI were followed by Wennerstrom et al. [13] for a
mean of 17 years. They demonstrated that the glom-
erular filtration rate was well-preserved in all children
with unilateral or no renal scarring, whereas a few
children with bilateral scarring showed some degree
of impairment of their renal function [13]. They per-
formed 24-hour blood pressure recordings in all chil-
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dren with scars. The blood pressure curves were
identical in children with and without scars. They
also reported a low risk of hypertension 2 decades
after childhood UTI, with mean systolic or diastolic
blood pressure above þ2 SD in 9% of the patients in
the scarring group and in 6% of those in the non-
scarring group [14].
In this context, it is useful to consider new patient
data that were obtained from the Australia and New
Zealand Dialysis and Transplant Registry [15], col-
lected between the years 1972 and 1988, when the
policy of optimum treatment of VUR was adopted.
These data show that intensive investigation and treat-
ment of children with febrile UTI has not been
accompanied by the expected reduction in the inci-
dence of ESRD attributable to reflux nephropathy
[15].
The Importance of VUR
It is well-known that significant VUR is associated
with recurrent febrile UTI, which can result in renal
scarring [6, 16]. This is particularly true for higher-
grade VUR, grade III or IV. On the other hand,
acute lesions of a clinically notable size may develop
even in the absence of VUR [17]. Significant VUR is
usually associated with abnormal bladder function and
initial abnormal renal scans [18]. It is therefore under-
standable that a lot of emphasis was laid on the detec-
tion and treatment of VUR in childhood. This is
because it was believed that ESRD attributable to
reflux nephropathy was preventable by the active treat-
ment of children with VUR, with long-term antibiotics
and ureteric reimplantation surgery.
However, it is noteworthy that several major de-
velopments have changed this approach. Over the
past 6 years, important studies have evaluated the
impact of long-term antibiotics on the recurrence
rate of febrile UTIs and on the development of
renal scars [6]. Studies have also investigated whether
surgical treatment of VUR reduced subsequent renal
scarring. Such studies have inferred that the clinical
benefit of these surgical interventions is marginal
[19].
Population studies have shown that in a large ma-
jority of cases, VUR depletes away with the passage
of time. This can take quite many years, but after a
10-year follow-up, VUR was persistent in only a
small minority of children [20].
Journal of Tropical Pediatrics Vol. 59, No. 6
J. A. KARI AND K. TULLUS
Prophylactic Antibiotics for Preventing Recurrent
UTI in Children
Prophylactic antibiotics have been used by most
pediatricians as a routine measure in children with
VUR. However, recent evidence concludes that
prophylaxis should not be routinely recommended.
In the recent AAP clinical practice guidelines, they
performed a meta-analysis of the raw data of six
most recent randomized controlled clinical trials
(RCTs) involving 1091 infants (2–24 months of
age). The result of this meta-analysis did not support
the use of antimicrobial prophylaxis to prevent fe-
brile recurrent UTI in infants without VUR or with
grade I–IV VUR. Only five infants with grade-V
VUR were included in the RCTs; therefore, no con-
clusion could be drawn in that group [6]. Similarly,
the Cochrane group reviewed 12 RCTs (involving
1557 children), with six comparing antibiotics with
placebo/no treatment. When all studies were
included, antibiotics did not appear to reduce the
risk of symptomatic UTI. However, when they eval-
uated the effects of antibiotics only in studies with low
risk of bias, there was a statistically significant reduc-
tion in UTI. The Cochrane group concluded that
long-term antibiotics appeared to reduce the risk of
repeat symptomatic UTI in susceptible children, but
the benefit was small and must be considered together
with the increased risk of microbial resistance [21].
Treatment or prophylaxis is unnecessary in chil-
dren with asymptomatic bacteriuria [22].
Surgery for VUR to Prevent Renal Scarring
A large European reflux study randomized children
with grade-III and -IV VUR to either have their
reflux surgically corrected or have treatment with
prophylactic antibiotics. No differences were found
between the two groups in the proportion of children
who had developed new renal scars, neither at the 5-
nor at the 10-year follow-up [23]. In a study from
Great Ormond Street Hospital for Children, the au-
thors assessed the kidney function by measuring the
glomerular filtration rate of children treated with sur-
gery or antibiotics for 10 years, and similarly, no dif-
ference was found between the two groups [24].
Prophylactic antibiotics were reported to prevent re-
current febrile UTIs and new renal damage in girls
with dilated VUR, in a well-designed Swedish study
that compared surgery, prophylactic antibiotics and
surveillance in children with VUR [25].
Which Investigations Should Be Done?
The current recommended diagnostic strategies tend
to minimize the number of unnecessary investiga-
tions, preferring those that are less invasive and
that expose children to the smallest radiological
risk. As the target of therapy is the prevention of
parenchymal damage and not the detection of
Journal of Tropical Pediatrics Vol. 59, No. 6
clinically insignificant VUR (non-dilated ureters,
normal bladder function and normal initial renal
scans), we should focus investigations on children
at risk of having major or significant malformations.
This includes children with recurrent UTI or any of
the following atypical UTI presentations, according
to NICE guidelines [7]:
(i) Impaired urine flow
(ii) Palpable mass in the abdomen
(iii) Serious septic presentation
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(iv) Bacteremia
(v) Increased serum creatinine
(vi) Slow response to treatment—no notable
improvement within 48 hours
(vii) Infection with a non-Escherichia coli bacteria
(viii) Any prenatal urinary tract finding
The NICE recommends that for infants younger
than 6 months with the first UTI and without atyp-
ical features, only renal ultrasound is recommended
within 6 weeks [7]. Only those with recurrent UTI or
atypical UTI should have renal ultrasound during
acute infection as well as micturating cystourethro-
gram (MCUG) and Tc-99 m dimercaptosuccinic acid
(DMSA) 4–6 months after acute infection (Table 1)
[7]. Similarly, the AAP guidelines recommend that
febrile infants and young children (2–24 months)
with UTIs should undergo renal and bladder ultra-
sound (evidence quality: C; recommendation) [6].
They recommend also that MCUG should not be
performed routinely after the first febrile UTI;
MCUG is indicated if ultrasound reveals hydrone-
phrosis, scarring or other findings that would suggest
either high-grade VUR or obstructive uropathy as
well as any other atypical or complex clinical circum-
stances (evidence quality: B; recommendation)
(Table 2).
The AAP also recommends further evaluation for
recurrent febrile UTI (Table 2) [6]. The NICE recom-
mends fewer investigations for young children aged
6 months to 3 years (Table 1) [7]. For the first UTI
with no atypical feature, no investigations are recom-
mended. Ultrasound during acute infection is recom-
mended only for children with atypical UTI, and it
should be performed within 6 weeks for those with
recurrent UTI. In both cases, it is necessary to per-
form a DMSA scan 4–6 months after acute infection
[7]. For children aged 3 years or older, the NICE
recommends ultrasound during the infection only if
the children presented with atypical UTI, whereas in
those with straightforward presentation, no radio-
logical investigations are required. For children
with recurrent UTI, ultrasound within 6 weeks is
required, followed by DMSA scan 4–6 months after
acute infection (Table 1).
The results of antenatal screening play an import-
ant role in deciding investigations for UTI. If ante-
natal ultrasound is to be relied on when choosing
post-UTI investigations, it is vital that it is performed
467
 J. A. KARI AND K. TULLUS

TABLE 1
NICE recommendation for imaging schedule for infants and childrena

US during the acute infection No Yes Only for infants

<6 months
US within 6 weeks Only for infants No Above 6 months old
<6 months
DMSA 4-6 months after No For children up to Yes
acute infection 3 years old
MCUG No Only for infants Only for infants
<6 months <6 months

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DMSA, dimercaptosuccinic acid; MCUG, micturating cystourethrogram; NICE, National Institute for Health and Clinical
Excellence; US, ultrasound; UTI, urinary tract infection.
a
Data adapted from the National Institute for Health and Clinical Excellence [7].

stasis predispose these children to developing recur-

TABLE 2 rent UTI. Proper evaluation and management is
AAP recommendation for imaging schedule for infants mandatory to prevent UTI and damage to the
(2–24 months)
kidneys.
Test Respond Severe clinical Recurrent
well illness or UTI Conclusion
no response

US during No Yes Not (i) The evaluation of UTIs should focus on

the acute mentioned
infection
US later on Yes Yes Yes
MCUG No Yes þ Yes
abnormal
US
AAP, American Academy of Pediatrics; MCUG, mictur-
ating cystourethrogram; US, ultrasound; UTI, urinary
tract infection.
in a structured and reliable manner, as an organ
screening/malformation screening program in all
children in the population. Unfortunately, this is
not the case in most countries, in the developing as
well as in the developed parts of the globe.
DMSA scan is recommended, as it can be used to
detect children with risk of having dilated VUR. [26].
Normal DMSA of both kidneys is associated with
early resolution of VUR in infants and normal blad-
der function in the majority of them, whereas abnor-
mal kidneys are associated with severe VUR and
abnormal bladder function. Therefore, abnormal
renal scans are an important independent predictor
of early failure to resolve VUR [27], whereas a
normal DMSA scan makes MCUG unnecessary in
the primary examination of infants with UTI [28].
Bowel Bladder Dysfunction
Voiding dysfunction and chronic functional consti-
pation could be the underlying causes of recurrent
UTI, without congenital or anatomical abnormalities
[29, 30]. Abnormal bladder pressure and urinary
renal status rather than presence or absence
of VUR.
(ii) Focus radiological investigations on children at
risk (recurrent UTI or atypical presentation).
(iii) MCUG is indicated in patients with positive
DMSA scan or recurrent febrile UTI. With
this approach, MCUGs will be avoided in up
to 50% of the children.
(iv) More investigations might be justified in de-
veloping countries with a higher risk of diag-
nostic delay and fewer prenatal ultrasound
scans.
(v) Do not use antibiotic prophylaxis routinely.
(vi) Overinvestigation of low-risk patients and over-
treatment of clinically insignificant VUR will be
avoided when new guidelines are followed.
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