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ORIGINAL ARTICLE
Managing children under 36 months of age with febrile
urinary tract infection: a new approach
Marco Pennesi &Ines L’Erario &Laura Travan &
Alessandro Ventura
Received: 2 May 2011 / Revised: 24 November 2011 / Accepted: 24 November 2011 / Published online: 11 January 2012
#IPNA 2011
Abstract
Background Recent guidelines on urinary tract infection
(UTI) agree on reducing the number of invasive procedures.
None of these has been validated by a long-term study. We
describe our 11-years experience in the application of a
diagnostic protocol that uses a reduced number of invasive
procedures.
Methods We reviewed retrospectively the records of 406
children aged between 1 and 36 months at their first UTI.
All patients underwent renal ultrasound (RUS). Children
with abnormal RUS and those with UTI recurrences under-
went voiding cystourethrography (VCUG) and dimercapto-
succinic acid (DMSA) renal scans.
Results RUS after the first UTI was pathological in 7.4%
children; 4.4 % had a second UTI. We performed 48 VCUG:
14 patients (29%) had vesicoureteral reflux (VUR), 12 of
which showed an abnormal RUS while 2 had recurrent UTI.
After DMSA renal scan renal damage appeared in only 6 of
them (12.5%); all these children showed grade IV VUR.
Conclusions The application of our guidelines leads to a
decrease in invasive examinations without missing any useful
diagnoses or compromising the child’shealth.
Keywords Urinary tract infection .Renal scars .
Vesicoureteral reflux .Antibiotic prophylaxis
Introduction
The National Institute for Health and Clinical Excellence
(NICE) guidelines on urinary tract infections (UTI) in child-
hood, published in 2007 [1], may lead to an epochal change
in the management of children with UTI. The application of
these guidelines could decrease significantly the use of
instrumental evaluations in children with UTI in the first
years of life. Based on these protocols other guidelines have
been developed such as the recent American Academy of
Pediatrics guidelines (AAP) [2].
One of the main objections against these more conserva-
tive approaches is that these guidelines derive from an
inadequate review of the literature, reflecting an “opinion
rather than a fact”[3]. Also, according to some authors, the
generalized application of these protocols could lead to a
lack of prevention of kidney damage in children with UTI
and vesicoureteral reflux (VUR) [4].
Since 1997 we have been using a diagnostic protocol
similar to that proposed by the recent NICE guidelines [5].
The main difference between our approach and the NICE
guidelines is that while NICE recommends renal ultrasound
(RUS) after a first UTI only in children younger than
6 months, and in the case of an atypical UTI (for a detailed
description of the definition of atypical UTI see Mori et al.
[1]), our protocol prefigures RUS on all patients regardless
of age, as also suggested by the AAP guidelines and Craig et
al. [2,6]. The aim of this study was to describe 11 years’
experience of applying our protocol in children up to
36 months with febrile UTI.
M. Pennesi (*):I. L’Erario :A. Ventura
Department of Pediatrics, Institute for Child and Maternal Health,
IRCCS Burlo Garofolo,
Via dell’Istria 65/1,
34137 Trieste, Italy
e-mail: pennesi@burlo.trieste.it
L. Travan
Department of Neonatal Intensive Care Unit,
Institute for Child and Maternal Health, IRCCS Burlo Garofolo,
Via dell’Istria 65/1,
34137 Trieste, Italy
Pediatr Nephrol (2012) 27:611–615
DOI 10.1007/s00467-011-2087-3
Materials and methods
Subjects
We reviewed the medical records of all children seen at the
Emergency Room of the Institute for Child and Maternal
Health, IRCCS Burlo Garofolo in Trieste, Italy, for their first
episode of symptomatic UTI. All patients were referred to the
Pediatric Nephrology Department for further assessment.
All recurrences were referred to us by the primary care
pediatricians or the Emergency Room. Overall, 510 patients
were identified. One hundred and four were excluded be-
cause they were lost at follow-up or because they lacked
some information (i.e., bacterium type or incomplete med-
ical records). Therefore, 406 patients (79.6% of the total),
aged between 1 and 36 months with symptomatic UTI, were
included in the study.
Symptomatic UTI was defined as fever (rectal temperature
>38°C), positive result to urinalysis (presence of leukocytes≥
50/mm
3
and bacteria≥10/mm
3
at optical microscopy), and
positive results to urine culture (1 million colony-forming
units/mL) for the same bacterium in two different samples.
Urine for urinalysis and urine culture was collected using
clean catch or bladder catheterization [1,2,7].
All children were treated with conventional antibiotic ther-
apy (oral ceftibuten, cefaclor, or amoxicillin/clavulanate for
10 days). None of the children had antibiotic prophylaxis.
Diagnostic protocol
All children underwent an RUS (Ansaldo Idea, with a multi-
frequency 7.5-MHz to 10-MHz probe for children younger
than 1 year or a convex multi-frequency for older chil-
dren) performed by skilled radiologists 1 month after the
first UTI. Those with normal RUS did not undergo any
further investigations and did not start any prophylactic
antibiotic therapy. Those with abnormal RUS (either
abnormal renal length—maximum longitudinal diameter
<5th percentile—ureteral dilatation, pelvic dilatation or
abnormal cortico-medullary differentiation) underwent a
voiding cystourethrography (VCUG) 2 months after the
acute episode. In all of these children a dimercaptosuc-
cinic acid (DMSA) renal scan was also performed
6 months after the acute episode. A DMSA renal scan
was performed with 99mTC-dimercaptosuccinic acid at a
dosage of 0.5 MBq/kg body weight (minimum 10 MBq);
image acquisition (6 projections—SPECT) was performed at
least 3 h after injection. DMSA scans were considered abnor-
mal when one area of decreased cortical DMSA uptake was
observed (suggesting the presence of renal scars, paying at-
tention to avoid considering central defects located over the
pelvicalyceal system as abnormal. Separate renal function
<45% with or without focal defects was considered abnormal.
At each episode of fever after the first UTI episode or
when symptoms of UTI occurred (e.g., change in the smell
of urine, anorexia, irritability), urinalysis and urine culture
were performed. All children with UTI recurrence and initial
normal RUS, were subjected to a second RUS, VCUG (after
2 months) and to a renal DMSA scan (after 6 months).
Figure 1shows the diagnostic flow chart. All children with
an abnormal RUS were monitored echographically once a
year, in order to evaluate the growth of the kidneys. Children
with an abnormal renal DMSA repeated the examination after
2and6years.
12 VUR (6 IV grade)
(4 III d )
Abnormal RUS VCUG III grade)
(2 I grade)
(30)and
DMSA
Ig
()
4 abnormal DMSA
(all with IV grade VUR)
First febrile UTI
(406)
Normal RUS UTI recurrence
2 VUR (2 IV grade)
VCUG
(376) (18) 2 abnormal DMSA
Follow-up and
(all with IV grade VUR)
DMSA (g)
No UTI recurrence
Fig. 1 Diagnostic flow chart. In each box is reported the number of patients for each step of the protocol. UTI urinary track infection, RUS renal
ultrasound, VUR vesicoureteral reflux, VCUG voiding cystourethrogram, DMSA dimercaptosuccinic acid
612 Pediatr Nephrol (2012) 27:611–615
Results
Of the 406 children evaluated at the first UTI, 32% (130)
were boys and 68% (276) were girls. Mean age was
9.5 months (range 1–36 months, Table 1). Mean follow-up
period was 47.3 months (range 12–133 months). The bac-
teria causing the infections are described in Table 2. Forty-
six patients out of 406 had “atypical UTI.”However, in our
study it was not considered to be a risk factor because we
performed RUS on all febrile UTI, as nowadays recommen-
ded by AAP guidelines. All children, regardless of age,
underwent RUS 1 month after the first episode of UTI,
376 out of 406 children (92.6%) exhibited a normal RUS
while in 30 (20 under 6 months of age) out of 406 patients
RUS was abnormal (7.4%; Table 3).
Eighteen patients (all with a normal RUS) had a second
episode of UTI during follow-up (4.4%), 5 out of 18 were
males, mean age was 12.4 months (range 8–16 months) and
the mean interval between the first and the second episode
was 3.6 months (range 1-10 months). The second RUS,
performed 2 months after the recurrence, was normal in all
18 patients.
We performed 48 VCUGs: 30 in children with abnormal
RUS and 18 because of UTI recurrences. Fourteen out of 48
children (29%; 4 boys and 8 under 6 months of age)had VUR:
12 were from the 30 children with an abnormal RUS while 2
had recurrent UTI. The same 48 children underwent DMSA
renal scans: renal damage (decreased cortical DMSA uptake)
appeared in 6 children (12.5%; 4 out of 6 were under 6 months
of age); all of these showed VUR of grade IV.
Of the 30 patients who showed an abnormal RUS, 4
(13.3%) had renal scars and a VUR of grade IV. Of the 18
patients with UTI recurrence 2 (11.1%) showed renal scars
and a VUR of grade IV (Table 4, Fig. 1). None of the 6
children positive for DMSA showed worsening of the renal
damage during the follow-up.
Discussion
Recent guidelines [1,2,6] developed from analysis of the
literature on VUR and UTI, radically changed the approach
to this problem, simplifying the diagnostic and therapeutic
pathway for children with UTI. This study shows that the
application of our guidelines (although created in 1997 long
before recent protocols) leads to a significant saving of
invasive evaluations after the first UTI episode, without
compromising the child’s health.
UTI recurrence
Our data show that only 4.4% of children had a recurrence
after the first UTI, and this usually occurred shortly after the
first episode of infection (average 3.6 months). VUR was
found in only 2 out of 18 children who relapsed (11%). If we
had performed VCUG on all patients at the first UTI, we
could have expected about 120 VUR (30%) [8]; however,
only2ofthesepossiblemisseddiagnosesresultedina
relapse and both patients had a high grade of VUR (IV).
It is likely that most of the undiagnosed VURs are of
lower grade and children presenting with them are not
expected to have higher rates of recurrence. Moreover, these
Table 2 Germ type at first urinary tract infection (UTI) and number of
UTI recurrences
Germ type Number of patients
at first UTI (%)
Number of UTI
recurrence (%)
Escherichia coli 366 (90.2) 15 (83)
Enterococcus 16 (4) 2 (11)
Proteus 13 (3.2) 1 (6)
Klebsiella 5 (1.2) 0 (0)
Pseudomonas aeruginosa 4 (0.9) 0 (0)
Streptococcus aureus 2 (0.5) 0 (0)
Table 3 Abnormality of renal ultrasound (RUS) and grade of vesi-
coureteral reflux (VUR) at voiding cystourethrography (VCUG)
Abnormality
of RUS
Number of patients
(under 6 months)
VCUG
(grade of VUR)
Pyelectasis 18 (10) 4 (2 III, 2I)
Pelvicalyceal system dilatation 2 (2) 2 (2 IV)
Hydronephrosis 6 (6) 6 (4 IV, 2 III)
“Medical kidney”4 (0) 0 (0)
Table 4 Dimercaptosuccinic acid (DMSA) renal scans and voiding
cystourethrography (VCUG)
Selection criteria VCUG VUR (grade) DMSA (scar)
Abnormal RUS (30) Positive (12) 6 (IV) 4
4 (III) 0
2 (I) 0
UTI recurrence (18) Positive (2) 2 (IV) 2
Table 1 Age at first urinary tract infection (UTI; months)
Age at first UTI Number of patients Percentage
1–6 178 43.8
7–12 136 33.5
13–24 66 16.3
25–36 26 6.4
Pediatr Nephrol (2012) 27:611–615 613
low and medium grade (grades I–III) VURs have a high
probability of spontaneous resolution in the first years of life
[9] and would not even require antibiotic prophylaxis [2,7,
10]. These considerations suggest that it is unreasonable to
perform VCUG at the first UTI occurrence.
Age
As in the NICE [1] guidelines, age under 6 months was not
considered to be a risk factor by itself. VCUG does not seem
to be justified in the first instance in the absence of any
proven recurrence. In fact, none of the 178 children under
6 months (96 boys and 82 girls) had UTI recurrences. Eight
of these children (4 boys and 4 girls) had VUR and all of
them had an abnormal RUS with pyelectasis or pelvicalyceal
system dilatation.
Renal damage
In our sample group renal damage was restricted to children
with a high grade of VUR (IV), while all but 2 of the
children who presented with a recurrence of UTI did not
show decreased cortical uptake on the DMSA scan. These
data, according to recent literature [11–13], show that VUR
is associated with “congenital”renal dysplasia, and does not
determine renal damage itself. In fact, it has by now been
largely demonstrated that renal dysplasia is associated with
grade IV/V VUR and has its own natural progression to renal
failure independently of pyelonephritis recurrences [14].
Renal ultrasound
As underlined before, the only difference between our pro-
tocol and the NICE guidelines [1] is in the selection of
which patients should undergo RUS. While NICE recom-
mends RUS only in patients aged under 6 months if no other
risk factor is present, we have been performing it on all
patients with UTI, as also suggested in the AAP guidelines
[2]. In fact the AAP recommended RUS in all febrile UTI
cases to detect anatomical abnormalities that require further
evaluation, such as additional imaging or urological consul-
tation. We performed 178 RUS in children under 6 months
and 228 in children over 6 months. Among younger chil-
dren, 18 were abnormal, while in those older than 6 months,
12 showed alterations. Following NICE guidelines we
would have spared 228 renal ultrasounds, while losing 2
children out of 4 VUR diagnosed in this age group (the rest
were diagnosed because of UTI recurrence). These data
suggest that RUS in children older than 6 months could be
limited only to those with atypical UTI (as in the NICE
guidelines).
We have demonstrated that the application of our guide-
lines results in a substantial saving of invasive investigations
(88% of VCUG in our sample), without any evident clinical
risk for the child in terms of renal damage and/or UTI
recurrences. As suggested by Coulthard [15], it is possible
that the diagnosis of UTI defined as fever >38.5°C (rectal)
and positive urine specimen, may lead to an overestimation
of pyelonephritis in febrile UTI episodes. However, it is
equally true that, as many studies have demonstrated
[16–18], the best approach for preventing renal damage is
not searching for VUR itself, but rather early diagnosis and
treatment of the infection. From this perspective the possible
over-diagnosis of pyelonephritis is a small price to pay
compared with the substantial simplification of the proce-
dures and with the reduction of invasive evaluations
obtained by using our flow chart. Recently, Coulthard [19]
and Venhola and Uhari [20], despite their diametrically
opposed viewpoints on VUR, reached the same conclusion:
the only reasonable strategy for preventing renal scars is the
prompt diagnosis and correct treatment of UTI.
As suggested by recent guidelines [1,2], our study seems
to confirm that a diagnosis of pyelonephritis with normal
RUS does not require searching for VUR. Perhaps in the
future, only DMSA will be necessary in febrile UTI follow-up,
and searching for VUR will become unnecessary.
Conclusion
We believe that the application of our guidelines to everyday
clinical practice will help to reduce the need for invasive
medical examinations while preserving children’s health.
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