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Journal of Pediatric Urology (2017) xx, 1e7

Review Article

Urinary tract infection in children:


Diagnosis, treatment, imaging e
Comparison of current guidelines
a
Department of Pediatrics with
Clinical Assessment Unit,
M. Okarska-Napierała a, A. Wasilewska b, E. Kuchar a
Medical University of Warsaw,
Poland Summary (EAU)/European Society for Pediatric Urology
(ESPU).
b
Department of Pediatrics and Background and objective Separate aspects of the approach for a child with
Nephrology, Medical University Urinary tract infection (UTI) is a frequent disorder of UTI, including diagnosis, treatment and further im-
of Bialystok, Poland
childhood, yet the proper approach for a child with aging studies, were compared, with allowance for
UTI is still a matter of controversy. The objective of recent research in each field.
Correspondence to: this study was to critically compare current guide-
M. Okarska-Napierała,
lines for the diagnosis and management of UTI in Conclusions
Department of Pediatrics with
Clinical Assessment Unit,
children, in light of new scientific data. The analyzed guidelines tried to reconcile recent
Samodzielny Publiczny reports about diagnosis, treatment, and further di-
Dziecie
˛cy Szpital Kliniczny, ul. Methods agnostics in pediatric UTI with prior practices and
_
Zwirki i Wigury 63A, Warszawa An analysis was performed of the guidelines from: opinions, and economic capabilities. There was still
02-091, Poland, Tel.: þ48 503 American Academy of Pediatrics (AAP), National a lack of sufficient data to formulate coherent, un-
065 849; fax: þ48 22 317 92 32 Institute for Health and Care Excellence (NICE), equivocal guidelines on UTI management in chil-
Italian Society of Pediatric Nephrology, Canadian dren, with imaging tests remaining the main area of
magda.okarska@gmail.com Paediatric Society (CPS), Polish Society of Pediatric controversy. As a result, the authors formulated
(M. Okarska-Napierała) Nephrology, and European Association of Urology their own proposal for UTI management in children.
Keywords
Congenital anomaly of the kid-
neys and urinary tract, CAKUT;
Urinary tract infection, UTI;
Voiding cystourethrogram, Care Excellence (NICE) guideline: Urinary
VCUG; Recommendations
Introduction
tract infection in under 16s: diagnosis and
UTI is the most common bacterial infection in management [6]. This was followed by
Received 21 May 2017
Accepted 29 July 2017 children aged <2 years [1], and it may be the American Academy of Pediatrics (AAP)
Available online xxx first symptom of congenital anomaly of the guideline: Urinary Tract Infection: Clinical
kidneys and urinary tract (CAKUT), with VUR Practice Guideline for the Diagnosis and
being the most prevalent. The assumption that Management of the Initial UTI in Febrile In-
recurrent UTIs in patients with VUR lead to fants and Children 2e24 Months, which was
renal scarring and consecutive chronic kidney published in 2011 [7]. In the same year, the
disease (CKD) had been the indication for ac- Italian Society of Pediatric Nephrology pub-
curate diagnosis and specific treatment of lished: Febrile urinary tract infections in
VUR. However, recently, this aggressive young children: recommendations for diag-
approach has been questioned, due to nosis, treatment and follow-up [8]. In 2014,
numerous studies undermining the clinical the Canadian Pediatric Society (CPS) released
importance and effectiveness of VUR treat- its guideline: Urinary tract infection in in-
ment [2]. Damage to the kidney tissue, which fants and children: Diagnosis and manage-
was previously attributed to UTIs or reflux ment [9]. In 2015, the Polish Society of
nephropathy, has been found to be congenital Pediatric Nephrology Guidelines concerning
in nature [3,4]. Similarly, antibiotic prophy- management of UTI in children was published
laxis in CAKUT has also been recently chal- [10]. The newest paper included in this
lenged [5]. The current review summarized analysis was: Urinary Tract Infections in
current knowledge and recommendations Children: EAU/ESPU Guidelines, which was
concerning UTI in children. published in 2016 by the European Associa-
The first document included in the review tion of Urology (EAU) and European Society
was the National Institute for Health and for Pediatric Urology (ESPU) [11].

http://dx.doi.org/10.1016/j.jpurol.2017.07.018
1477-5131/ª 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018
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2 M. Okarska-Napierała et al.

The guidelines substantially differ in rating evidence Diagnosis


quality and strength of recommendations. The NICE authors
revised evidence using separate criteria for interventions All guidelines agree that UTI in children may be difficult to
and diagnostic test accuracy, but they did not rate their diagnose, especially in children aged <2e3 years, because
recommendations. Similarly, neither CPS nor EAU/ESPU symptoms and signs in this age group are non-specific. For
guidelines included any rating system for strength of rec- this reason, urine tests are warranted not only in children
ommendations. The AAP guidelines are graded according to with typical UTI symptoms, but also in cases of unexplained
AAP policy; the Italian authors used Strength of Recommen- fever. This approach was reinforced by an AAP technical
dation Taxonomy (SORT) criteria, whereas Polish guidelines report from 2011, which stated that among children aged
were based on Grades of Recommendation Assessment, 2e24 months with fever of unknown origin, 5% had a UTI [19].
Development and Evaluation (GRADE) system. Thus, the In addition, AAP, CPS, Polish and EAU/ESPU guidelines
strength of recommendations was unsuitable for state that urine tests must be performed before antimi-
comparison. crobial treatment is introduced, whereas CPS guidelines
emphasize that in cases of fever with a known source (e.g.
diarrhea or rhinitis), urine tests should not be performed.
Definitions In toilet-trained children, the method of choice for
diagnosing a UTI is a clean voided midstream urine sample
A few guidelines included definitions of atypical/compli- [20]. The difficulty is obtaining a urine sample from a child
cated or recurrent UTI. According to NICE, atypical UTI who does not control voiding. There are four techniques for
include: seriously ill patients, children with poor urine flow, collecting a urine sample in those children. Non-invasive
abdominal or bladder mass, elevated serum creatinine, techniques include a bag applied to the perineum and
septicemia, failure to respond to treatment with suitable clean catch midstream void, whereas invasive methods
antibiotics within 48 h, and infections with non-Escherichia include bladder catheterization and suprapubic aspiration
coli organisms. In both CPS and Polish guidelines, almost (SPA). The NICE guidelines recommend a clean catch sam-
identical characteristics are listed as features of complicated ple as the method of choice, but they also permit a urine
UTI, and both latter guidelines cite NICE as a reference. collection bag. However, an AAP technical report states
In addition, the NICE guideline separately lists risk factors that up to 85% of positive culture results obtained by using a
for serious underlying pathology, which include: poor urine collection bag can be false positives [19]. For this reason,
flow, history of previous UTI, recurrent fever of uncertain most guidelines published since 2011 agree that a urine
origin, antenatal diagnosis of renal abnormality, family sample collected in a bag applied to the perineum is only
history of VUR or renal disease, constipation, dysfunctional reliable when negative. Most guidelines recommend clean
voiding, enlarged bladder, abdominal mass, evidence of catch void as the preferred method, although, according to
spinal lesion, poor growth, and high blood pressure. AAP, only invasive techniques may be used to confirm
Italian guidelines similarly define risk factors for CAKUT diagnosis of a UTI. The reason for this is probably that AAP
as follows: prenatal or postnatal ultrasonographic abnor- guidelines relate to children aged up to 24 months, in whom
malities, family history of VUR, septicemia, renal insuffi- mid-stream void has a high contamination rate of up to 26%
ciency, male infants aged <6 months, suspected non- [21], and is technically difficult and time-consuming. The
compliant family, micturition abnormalities or thickened CPS guidelines also recommend invasive techniques in
bladder wall, absence of a clinical response to antibiotics children up to 24 months of age.
within 72 h, and pathogens other than E. coli. Some guidelines also suggest that invasive urine sam-
A recurrent UTI is defined in the NICE guideline as two or pling methods are particularly appropriate in children who
more episodes of pyelonephritis, or one episode of pyelo- appear ill or have poor general health when there is an
nephritis plus one or more episodes of cystitis, or three or urgent need for antimicrobial treatment. The AAP technical
more episodes of cystitis. The other guidelines provide no report also states that SPA has higher pain scores and lower
other definition of recurrent UTI. success rates than bladder catheterization, which in turn
Most of the risk factors listed above seem to be based on presents 95% sensitivity and 99% specificity in comparison
experts’ opinion, which explains the slight differences be- with SPA [19]. This suggests catheterization as a preferred
tween the guidelines. Scientific data on risk factors pre- invasive urine sampling method.
dicting CAKUT in children with a first-time UTI are scarce
and conflicting. Male gender, young age, positive family
history [12], fever of 38  C, elevated CRP [13], high Urinalysis
neutrophil ratio [14], pathogens other than E. coli, and
positive blood culture [15,16] were all found to predict VUR Urinalysis is a quick dipstick test for nitrite and leukocyte
in children with UTI. However, a recent study by Yılmaz esterase, and microscopic examination for white blood
evaluated 300 children with their first UTI, and no clinical cells (WBC) and bacteria. The nitrite dipstick test repre-
or laboratory data were found to correlate with the pres- sents the conversion of dietary nitrate by Gram-negative
ence of VUR [17]. On the other hand, Ristola et al., in a bacteria, and has high specificity (98%) for UTI [22]. Its
study evaluating 282 children with their first UTI, found major limitation is that it gives negative results when the
that non-E. coli UTIs correlated with abnormal kidney ul- bladder is emptied frequently or if the underlying pathogen
trasound, whereas risk factors predicting VUR included is Gram-positive [23]. Therefore, most guidelines agree
abnormal ultrasound, atypical infection, non-E. coli infec- that a urine dipstick test is not recommended for the
tion, and recurrent infections [18]. youngest children who void frequently. Leukocyte esterase,

Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018
+ MODEL
Urinary tract infection in children 3

a surrogate marker of pyuria, has sensitivity of 79% and febrile children with a UTI is less effective than a 7-day
specificity of 87% for UTIs [22]. regimen, which is the reason for the recommended mini-
White blood cells present in the urine on microscopic ex- mum treatment duration of 7 days.
amination are a useful indicator of inflammation associated The choice of antibiotic should be based on locally
with UTI, although there is no standardized definition of developed current resistance patterns of urinary patho-
pyuria in the literature. In the microscopic analysis of gens. The AAP guidelines state that antibiotics excreted in
centrifuged urine, five WBCs per high-power field is a usual the urine, which do not reach therapeutic concentrations in
threshold for pyuria. Another method is automatic counting the blood (e.g. nitrofurantoin), should not be used in py-
in uncentrifuged urine, with 10 WBCs being a threshold value. elonephritis treatment. Another issue to be considered in
the treatment of UTI is the increasing frequency of in-
Cultures fections with extended-spectrum beta-lactamases (ESBL)-
The definition of significant bacteriuria varies slightly be- producing pathogens, which is reported to be 20% and is
tween guidelines. According to AAP, significant bacteriuria more common in younger children [19].
is defined as 5  104 colony forming units (CFU) per milli-
liter (CFU/ml) of urine obtained by catheterization. This
Further diagnostics
definition is derived from a study published in 1956. Urine
cultures from women with and without pyelonephritis
symptoms revealed that the threshold range, in which the Further diagnostics in children with febrile UTI is undoubt-
proportion of patients with symptomatic UTI exceeded edly the most controversial issue. The general tendency is
those without symptoms, was between 104 and 105 CFU/ml to restrict indications to VCUG and DMSA scintigraphy. Sig-
[24]. Hoberman et al. confirmed this threshold value in nificant radiation exposure, the risk of catheter-induced
children with UTI in a study in which urine culture results UTI, stress for a young patient and their parents, and the
were verified by a renal scan with DMSA [25]. Other cost of the imaging techniques must be considered. The
guidelines present broader definitions considering the urine main objective of performing imaging tests following a
collection method; they are presented in Table 1. UTI is to identify children with CAKUT, mainly VUR, who
The definition included in EAU/ESPU guidelines is based may be more susceptible to recurrent UTI and further renal
on the finding that pyelonephritis may also be present with scarring. Some of those patients may benefit from surgical
lower CFU counts on cultures. In 2016, Swerkersson et al. interventions. They may also benefit from antimicrobial
published an interesting study evaluating 430 infants with prophylaxis, which used to be routinely administered
first-time UTI, diagnosed by SPA, revealing that 19% of in children with CAKUT, and had been proven effective in
children had low bacterial counts of <104 CFU/ml. The reducing the risk of recurrent UTI in the Prevention of
authors suggested that UTI with low bacterial count might Recurrent Urinary Tract Infection in Children with Ves-
be a separate entity, associated with non-E. coli etiology icoureteric Reflux and Normal Renal Tracts (PRIVENT) study
and low inflammatory response, but with the same risk of [31]. This approach, however, has recently been chall-
VUR and renal scarring [26]. In another study, it was found enged by several studies demonstrating that antimicrobial
that 19% of infants with UTI diagnosed by SPA had bacte- prophylaxis in those children neither avoids subsequent
riuria <105 CFU/ml in clean catch voided urine [27] and infections nor influences further renal scarring [5,32].
could have been missed with a higher cut-off value. These Roussey-Kesler et al. found no benefit from antimicrobial
arguments suggest that the EAU/ESPU bacteriuria defini- prophylaxis in children with grade IeIII VUR, excluding boys
tions are probably the most appropriate for diagnosing UTI. with grade III VUR in whom it may avoid further UTI [33],
Children with positive urine culture and normal urinal- whereas a Swedish reflux study revealed that in a group of
ysis, without symptoms, are regarded as having asymp- infant girls with grade III or IV VUR, antimicrobial prophy-
tomatic bacteriuria that, in otherwise healthy subjects, is laxis is effective in preventing renal scarring [34]. On the
not an indication for any intervention. This applies to all other hand, the recent Randomized Intervention for Chil-
guidelines analyzed in the current review. dren with Vesicoureteral Reflux (RIVUR) trial has proven
that antimicrobial prophylaxis reduces risk of UTI recur-
rence, but not of renal scarring in children with VUR [35].
Management The benefit of diagnosing VUR has also been questioned
for other reasons. Several studies have stated that the risk
The varying approaches to management of UTI included in of VUR in children with UTI is similar to the rest of the
guidelines are summarized in Table 1. The AAP authors population at around 30% [19,36]. Moreover, a large pro-
stated that there is no difference in efficacy between oral portion of children with UTI and VUR, particularly low-
and intravenous treatment of UTI, which has been proven in grade, reach spontaneous resolution without medical
numerous studies both in children and adults [28,29]. Thus, intervention [37] and mild/moderate VUR does not increase
most children with a UTI can be treated orally. Parenteral the risk of recurrent UTI or renal scarring [38]. The question
treatment is only required in children who are severely ill is: how to identify those children with VUR who would
or unable to retain oral intake; however, sequence treat- benefit from surgical treatment?
ment is recommended even in those children.
The AAP guidelines suggest that pyelonephritis treat- Abdominal ultrasound
ment should last 7e14 days. This broad range is due to the
lack of sufficient data identifying optimal treatment dura- Abdominal ultrasound (US) is the least invasive, and rela-
tion [30]. There is evidence that a 1e3-day regimen for tively inexpensive, diagnostic tool in evaluating children

Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018
Table 1 Comparison of the guidelines.

4
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018
Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e

NICE 2007 AAP 2011 ISPN 2011 CPS 2014 PSPN 2015 EAU/ESPU 2016 Our proposal References
of recommendation
Urine collection Clean catch Bladder Bladder No Any method for Clean catch Bladder Finnell 2011
in non-toilet- mid-stream void catheterization catheterization recommendation, urinalysis mid-stream void, catheterization Tosif 2012
trained Alternatively: or SPA (relates (in poor general but bladder Clean catch bladder or clean catch
children collection bag to children aged health) or clean catheterization mid-stream catheterization mid-stream void
<2 years) catch mid-stream or clean catch void, bladder or SPA for diagnosis Collection bag
void (method of mid-stream void catheterization Collection bag only as a method
choice) are the preferred or SPA for only as a method of exclusion
Collection bag is methods culture of exclusion
acceptable for
urinalysis, not
for culture
Significant Not included Catheterization: Catheterization: Catheterization: >5  104 or Catheterization: Catheterization: Hoberman
bacteriuria 5  104 CFU/ml >104 CFU/ml >104 CFU/ml (depending on the 103e105 CFU/ml 103 CFU/ml 1994
Clean voided laboratory standard) Clean voided Clean voided Swerkersson
urine: >105 Clean voided urine: >105 CFU/ml urine: >104 CFU/ml urine: >104 2016
CFU/ml SPA: any growth of bacteria with symptoms CFU/ml with
Urinary bag: OR >105 without symptoms OR >105

+
>105 CFU/ml symptoms without symptoms

MODEL
SPA: any growth SPA: any growth of
of bacteria bacteria
Route of Parenteral in all Parenteral only Parenteral only Parenteral only in Parenteral in Parenteral in all Parenteral only Hoberman
antibiotic children <3 in children unable in children unable children unable to most children children <2 months in children unable 1999
administration months and in to eat and/or in to eat and/or in eat and/or in poor <3 months and and in those who to eat and/or in Pohl 2007
those who are poor general health poor general health general health in those who are unable to poor general
unable to eat Parenteral Parenteral are unable to eat and/or in health
and/or in poor antibiotics should antibiotics should eat and/or in poor general Parenteral
general health be switched to be switched to poor general health antibiotics should
Parenteral oral as soon as oral after 2e4 health be switched to
antibiotics should clinical days oral as soon
be switched to improvement is as clinical
oral after observed improvement is
2e4 days observed

M. Okarska-Napierała et al.
Oral in Oral in all Oral in all Oral in all Oral in all Oral in all Oral in all
other children other patients other patients other patients, other patients other patients other patients
>3 months but children <3
months; need
close monitoring
Treatment Upper UTI: 7e10 7e14 days 7e14 days Upper UTI: 7e14 Upper UTI: Upper UTI: 7e14 Upper UTI: 7e10 Strohmeier
duration days days 7e10 days days days 2014
Lower UTI: 3 days Lower UTI: 2e4 Lower UTI: Lower UTI: at Lower UTI: 3
days 3e5 days least 3e5 days days
SPA e suprapubic aspiration; CFU e colony forming units.
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Urinary tract infection in children 5

with UTI. It is usually readily available and can detect method (DMSA scan and, if positive, VCUG) in all patients
hydronephrosis, hydroureters, bladder wall abnormalities, with febrile UTI and aged <1 year. In older children,
and acute complications of UTI (e.g. renal or perirenal ab- exclusion of VUR is warranted in all girls, and in those boys
scesses). On the other hand, US has limited sensitivity in who have recurrent UTI. Bottom-up and top-down ap-
detecting VUR and is highly observer-dependent. According proaches were compared by Routh et al., who revealed that
to NICE, US is indicated in all children with UTI and aged <6 the top-down method results in a higher radiation dose,
months, whereas in older children responding well to ther- higher cost and lower sensitivity compared with the
apy, routine US is not needed. This restrictive approach is bottom-up approach, which may not outweigh its benefits
definitely cost-effective [39] but carries a risk of missing a (fewer urethral catheterizations and fewer diagnoses of
significant number of patients who may benefit from CAKUT insignificant VUR) [39]. This is in contradiction to CPS
diagnosis [40]. According to most of the remaining guide- guidelines, which recommend DMSA as a first choice diag-
lines, US is indicated in those children with UTI who are aged nostic test in girls, and follow-up modality in both sexes.
<2 years or present with additional risk factors (Table 2).
DMSA scan
VCUG
A DMSA scan is reliable in detecting both acute pyelone-
VCUG is a gold standard for the diagnosis and grading of phritis and late renal parenchymal scarring. However, it
VUR [41]. It is also useful in visualizing the anatomy of the usually does not affect acute clinical management. A DMSA
urethra and bladder. The disadvantages of this method scan is an expensive technique that exposes the patient to
include radiation exposure, the risk of inducing a UTI, the radiation. Mantadakis et al. studied the accuracy of acute
high cost and discomfort for the patient. According to most phase DMSA scans in identifying children with VUR, and
of the analyzed guidelines, VCUG is not routinely indicated revealed that DMSA scans have limited ability to replace
and should only be performed if US reveals abnormalities VCUG in the diagnosis of VUR [42]. Indications for DMSA
suggesting CAKUT, or in other specific clinical circum- scans vary considerably between guidelines, which are
stances (Table 2). The EAU/ESPU, on the contrary, indicates probably due to their unclear role in further clinical de-
that US alone misses up to 33% of patients at risk and thus cisions (Table 2). Moreover, EAU/ESPU guidelines recom-
recommends one of two further approaches: the bottom-up mend considering treatment of phimosis in uncircumcised
method (VCUG and, if positive, DMSA scan) or the top-down boys, who are at significantly higher risk of recurrent UTI.

Table 2 Comparision of further diagnostics.


Age of patients Ultrasound (US) VCUG DMSA
NICE <6 months All children Atypical/recurrent UTI Atypical/recurrent UTI
6 monthse3 years Atypical/recurrent UTI Atypical/recurrent UTI Atypical/recurrent UTI
AND specific featuresa
>3 years Atypical/recurrent UTI Not indicated Recurrent UTI
AAP 24 months All children Abnormal US or other e
specific circumstances
Italian 36 months All children Abnormal US or risk factorsb Abnormal US or VUR
CPS <2 years All children Abnormal US; recurrent Only when diagnosis of
>2 yrs. Not specified UTI in children <2 years UTI is in doubt
Polish <2 years All children Atypical/recurrent RECURRENT pyelonephritis,
>2 years Pyelonephritis, febrile UTI; abnormal US; VUR III-V
atypical/recurrent positive family history for VUR
UTI or risk factors
for recurrent UTIc
EAU/ESPU All children Either VCUG or DMSA is
indicated in bottom-up
or top-down approach
Our proposal <2 years All children Recurrent febrile UTI; Recurrent pyelonephritis,
>2 years CAKUT risk factors abnormal USG; other VUR IIIeV, high risk of
CAKUT risk factors renal scarring
NICE e National Institute for Health and Care Excellence; AAP e American Academy of Pediatrics; CPS e Canadian Paediatric Society;
EAU e European Association of Urology; ESPU e European Society for Pediatric Urology; US e ultrasonography; VCUG e voiding
uretherocystography; DMSA e dimercaptosuccinic acid scintigraphy; VUR e vesicoureteral reflux; CAKUT e congenital anomalies of the
kidney and urinary tract.
a
Dilatation on ultrasound, poor urine flow, non-E. coli infection, family history of VUR.
b
First degree relative with VUR, septicemia, chronic kidney disease, age <6 months in a male infant, likely non-compliance of the
family, abnormal bladder emptying, no clinical response to correct antibiotic treatment within 72 h, bacteria other than E. coli.
c
Abnormal US in past, positive family history of UTI or CAKUT, bladder catheterization, abnormal voiding, abnormal defecation or
sexual activity in girls.

Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018
+ MODEL
6 M. Okarska-Napierała et al.

Conclusions References

The guidelines on UTI in children try to reconcile recent [1] Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of uri-
reports on diagnosis, treatment, and further diagnostics nary tract infection in childhood: a meta-analysis. Pediatr
with prior practices and opinions, and costs. As stated Infect Dis 2008;27:302e8.
above, many studies concerning UTI in children are con- [2] Marks SD, Gordon I, Tullus K. Imaging in childhood urinary
tract infections: time to reduce investigations. Pediatr
flicting, and there is still a lack of sufficient data to
Nephrol 2008;23(1):9e17.
formulate coherent, indubitable guidelines, with imaging [3] Stock JA, Wilson D, Hanna MK. Congenital reflux nephropathy
diagnostics remaining the main area of controversy. In light and severe unilateral fetal reflux. J Urol 1998;160:1017e8.
of these analyzed guidelines, it is recommended that urine [4] Wennerström M, Hansson S, Jodal U, Stokland E. Primary and
tests be performed both in children with typical UTI acquired renal scarring in boys and girls with urinary tract
symptoms and in children with unexplained fever. Urine infection. J Pediatr 2000;136(1):30e4.
tests should be performed before administration of anti- [5] Pennesi M, Travan L, Peratoner L, Hoberman A, Mathews R,
microbials. In toilet-trained children, a clean voided Mattoo T, et al. Is antibiotic prophylaxis in children with
midstream urine sample is the method of choice for diag- vesicoureteral reflux effective in preventing pyelonephritis
nosing a UTI, while catheterization is a preferred invasive and renal scars? A randomized, controlled trial. Pediatrics
2008;122(6):1409e10.
method of urine sampling in infants and small children.
[6] National Institute for Health and Clinical Excellence (NICE).
Urine sample collected in a bag applied to the perineum Urinary tract infection in children. Available at: https://www.
can be used as a UTI exclusion method. nice.org.uk/Guidance/cg54 [Last Accessed 2 April 2017].
Both positive urinalysis and significant bacteriuria are [7] Roberts KB, Downs SM, Finnell SM, Hellerstein S, Shortliffe LD,
necessary to diagnose a UTI. Children with positive urine Wald ER, et al., American Academy of Pediatrics Subcom-
culture and negative urinalysis, without symptoms, are mittee on Urinary Tract Infection, Steering Committee on
regarded as having asymptomatic bacteriuria, which, in Quality Improvement and Management. Urinary tract infec-
otherwise healthy subjects is not an indication for any tion: clinical practice guideline for diagnosis and management
intervention. of the initial UTI in febrile infants and children 2 to 24 months.
It is recommended that the diagnosis of a UTI be Pediatrics 2011;128:595e610.
[8] Ammenti A, Cataldi L, Chimenz R, Fanos V, La Manna A,
dependent on the urine collection method, and that it is
Marra G, et al., Italian Society of Pediatric Nephrology. Febrile
defined by significant bacteriuria as >104 CFU/ml in clean urinary tract infections in young children: recommendations
voided urine with symptoms, 103 CFU/ml by catheteri- for the diagnosis, treatment and follow-up. Acta Paediatr
zation (depending on the laboratory standard), and any 2012;101(5):451e7.
growth of bacteria by SPA. [9] Robinson JL, Finlay JC, Lang ME, Bortolussi R, Canadian Pae-
Since there is no difference in efficacy between oral and diatric Society Infectious Diseases and Immunization Com-
intravenous UTI treatment, parenteral treatment is only mittee, Community Paediatrics Committee. Urinary tract
required in children who are severely ill or unable to retain infections in infants and children: diagnosis and management.
oral intake. Parenteral antibiotics should be switched to Paediatr Child Health 2014;19(6):315e25.
oral as soon as clinical improvement is observed, usually [10] [Polish Society of Pediatric Nephrology recommendations for
the management of children with urinary tract infection].
within 24e48 h. In children aged >3 months, the differen-
Available at: http://ptnfd.org/ [Last Accessed 27 March
tiation between upper and lower UTI guides the treatment. 2017].
Upper UTI treatment should last 7e10 days, whereas in [11] Stein R, Dogan HS, Hoebeke P, Kocvara R, Nijman RJ,
lower urinary tract infection this should be 3 days. The Radmayr C, et al., European Association of Urology and Eu-
choice of antibiotic should be based on local epidemiology ropean Society for Pediatric Urology. Urinary tract infections
and susceptibility patterns. in children: EAU/ESPU guidelines. Eur Urol 2015;67(3):546e58.
It is recommend that an abdominal US be performed on [12] Oostenbrink R, van der Heijden AJ, Moons KG, Moll HA. Pre-
all patients aged <2 years of age and older children with diction of vesico-ureteric reflux in childhood urinary tract
CAKUT risk factors. VCUG remains a gold standard for the infection: a multivariate approach. Acta Paediatr 2000;89(7):
diagnosis and grading of VUR and should be performed in 806e10.
[13] Soylu A, Kasap B, Demir K, Türkmen M, Kavukçu S. Predictive
children with abnormal abdominal US, recurrent UTI, or
value of clinical and laboratory variables for vesicoureteral
other risk factors (recommendation strength 1C). reflux in children. Pediatr Nephrol 2007;22(6):844e8.
The bottom-up method is recommended in evaluating [14] Lai SW, Ng KC. Retrospective analysis of inflammatory pa-
children with UTI: VCUG and, if positive, a DMSA scan. DMSA rameters in acute pyelonephritis. Scand J Urol Nephrol 2003;
scans should be performed 4e6 months after UTI in children 37(3):250e2.
with recurrent UTI, VUR grade IIIeV, and those who have [15] Jantunen ME, Siitonen A, Ala-Houhala M, Ashorn P, Föhr A,
high risk of renal scarring (i.e. scarring visible on US or Koskimies O, et al. Predictive factors associated with signifi-
clinical symptoms: hypertension, albuminuria). cant urinary tract abnormalities in infants with pyelonephri-
Nevertheless, clinicians treating children with a UTI tis. Pediatr Infect Dis J 2001;20:597e601.
should be aware of the existing controversy in order to [16] Marcus N, Ashkenazi S, Samra Z, Cohen A, Livni G. Community-
acquired enterococcal urinary tract infections in hospitalized
make good decisions.
children. Pediatr Nephrol 2012;27:109e14.
[17] Yılmaz S, Özçakar ZB, Kurt S‚ükür ED, Bulum B, Kavaz A,
Conflict of interest/funding Elhan AH, et al. Vesicoureteral reflux and renal scarring risk in
children after the first febrile urinary tract infection. Nephron
2016;132(3):175e80.
None.

Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018
+ MODEL
Urinary tract infection in children 7

[18] Ristola MT, Löyttyniemi E, Hurme T. Factors associated with [31] Craig JC, Simpson JM, Williams GJ. Antibiotic prophylaxis and
abnormal imaging and infection recurrence after a first febrile recurrent urinary tract infection in children. N Engl J Med
urinary tract infection in children. Eur J Pediatr Surg 2016; 2009;361(18):1748e59.
27(2):142e9. [32] Montini G, Rigon L, Zucchetta P, Fregonese F, Toffolo A,
[19] Finnell SM, Carroll AE, Downs SM, Subcommittee on Urinary Gobber D, et al. Prophylaxis after first febrile urinary tract
Tract Infection. Diagnosis and management of an initial UTI in infection in children? A multicenter, randomized, controlled,
febrile infants and young children. Pediatrics 2011;128(3): noninferiority trial. Pediatrics 2008;22(5):1064e71.
749e70. [33] Roussey-Kesler G, Gadjos V, Idres N, Horen B, Ichay L,
[20] Whiting P, Westwood M, Bojke L, Palmer S, Richardson G, Leclair MD, et al. Antibiotic prophylaxis for the prevention of
Cooper J, et al. Clinical effectiveness and cost-effectiveness recurrent urinary tract infection in children with low grade
of tests for the diagnosis and investigation of urinary tract vesicoureteral reflux: results from a prospective randomized
infection in children: a systematic review and economic study. J Urol 2008;179(2):674e9.
model. Health Technol Assess 2006;10(36). iiieiv, xiexiii, [34] Brandstrom P, Jodal U, Sillen U, Hansson S. The Swedish
1e154. reflux trial: review of a randomized, controlled trial in
[21] Tosif S, Baker A, Oakley E, Donath S, Babl FE. Contamination children with dilating vesicoureteral reflux. J Pediatr Urol
rates of different urine collection methods for the diagnosis of 2010;7:594e600.
urinary tract infections in young children: an observational [35] RIVUR Trial Investigators. Antimicrobial prophylaxis for chil-
cohort study. J Paediatr Child Health 2012;48(8):659e64. dren with vesicoureteral reflux. N Engl J Med 2014;370(25):
[22] Williams GJ, Macaskill P, Chan SF, Turner RM, Hodson E, 2367e76.
Craig JC. Absolute and relative accuracy of rapid urine tests [36] Hannula A, Venhola M, Renko M, Pokka T, Huttunen NP,
for urinary tract infection in children: a meta-analysis. Lancet Uhari M. Vesicoureteral reflux in children with suspected and
Inf Dis 2010;10:240e50. proven urinary tract infection. Pediatr Nephrol 2010;25(8):
[23] Whiting P, Westwood M, Watt I, Cooper J, Kleijnen J. Rapid 1463e9.
tests and urine sampling techniques for the diagnosis of uri- [37] Montini G, Zucchetta P, Tomasi L, Talenti E, Rigamonti W,
nary tract infection (UTI) in children under five years: a sys- Picco G, et al. Value of imaging studies after a first febrile
tematic review. BMC Pediatr 2005;5:4. urinary tract infection in young children. Paediatrics 2009;
[24] Kass E. Asymptomatic infections of the urinary tract. Trans 123(2):239e46.
Assoc Am Phys 1956;69:56e64. [38] Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A,
[25] Hoberman A, Wald ER, Reynolds EA, Penchansky L, Charron M. Young L. Clinical significance of primary vesicoureteral reflux
Pyuria and bacteriuria in urine specimens obtained by cath- and urinary antibiotic prophylaxis after acute pyelonephritis:
eter from young children with fever. J Pediatr 1994;124(4): a multicenter, randomized, controlled study. Pediatrics 2006;
513e9. 117(3):626e32.
[26] Swerkersson S, Jodal U, Åhrén C, Sixt R, Stokland E, [39] Routh JC, Grant FD, Kokorowski PJ, Nelson CP, Fahey FH,
Hansson S. Urinary tract infection in infants: the significance Treves ST, et al. Economic and radiation costs of initial im-
of low bacterial count. Pediatr Nephrol 2016;31(2):239e45. aging approaches after a child’s first febrile urinary tract
[27] Koskimies O. Diagnostic accuracy of urinary tract infection infection. Clin Pediatr 2012;51(1):23e30.
and subsequent development of renal scars. J Pediatr 1995; [40] Hassib N, Muhaned M, Asad AK, Abdulla A, Amar A. Renal tract
126(1):157e9. abnormalities missed in a historical cohort of young children
[28] Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, with UTI if the NICE and AAP imaging guidelines were applied.
Majd M, et al. Oral versus initial intravenous treatment for J Pediatr Urol 2015;11. 252.e1e252.e7.
urinary tract infections in young febrile children. Pediatrics [41] Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tammi-
1999;104(1):79e86. nen-Mobius TE. International system of radiographic grading
[29] Pohl A. Modes of administration of antibiotics for symptomatic of vesicoureteric reflux. International reflux study in children.
severe urinary tract infections. Cochrane Database Syst Rev Pediatr Radiol 1985;15:105e9.
2007;17(4), CD003237. [42] Mantadakis E, Vouloumanou EK, Georgantzi GG, Tsalkidis A,
[30] Strohmeier Y, Hodson EM, Willis NS, Webster AC, Craig JC. Chatzimichael A, Falagas ME. Acute Tc-99m DMSA scan for
Antibiotics for acute pyelonephritis in children. Cochrane identifying dilating vesicoureteral reflux in children: a meta-
Database Syst Rev 2014;28(7), CD003772. analysis. Pediatrics 2011;128(1):169e79.

Please cite this article in press as: Okarska-Napierała M, et al., Urinary tract infection in children: Diagnosis, treatment, imaging e
Comparison of current guidelines, Journal of Pediatric Urology (2017), http://dx.doi.org/10.1016/j.jpurol.2017.07.018