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D. BUONSENSO, L. CATALDI
cute pyelonephritis is the most common serious bacterial infection in childhood. About 7 to 8% of girls and 2% of boys
have a urinary tract infection (UTI) during
the first 8 years of life.1, 2 Febrile UTIs have
the highest incidence during the first year of
life in both sexes, whereas nonfebrile UTIs
occur predominantly in girls older than 3
years.2
Establishing the diagnosis is difficult in
early childhood due to the absence of specific symptoms, and difficulty in collection
of not contaminated urine samples without
invasive methods (urethral catheterization
or suprapubic aspiration [SPA]).
After infancy, UTIs confined to the blad-
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primary renal damage that precedes infection and scars related to UTI. Primary renal
damage is linked to prior obstruction, genetic and developmental factors that result
in maldevelopment (hypodysplasia) of the
urinary tract, or both. However, inflammatory processes (pyelonephritis) that occur
in the context of infection may also produce scars.27
In 2007, the United Kingdoms National
Institute for Health and Clinical Excellence
(NICE) 28 published new guidelines for the
management of UTI in children, which recommend more selective
use of renal ultrasonography (US) and
VCUG. Similarly, the 2011 American Academy of Pediatrics guidelines 29 do not recommend routine use of imaging techniques.
This new attitude could be of particular
interest, since current imaging, prophylaxis,
and prolonged follow-up strategies place
a heavy burden on patients, families, and
national health systems resources and carry
risks without evidence of benefit.
Methods
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administered; the specimen needs to be obtained through catheterization (95% sensitivity, 99% specificity) 30-32 or SPA, because
the diagnosis of UTI cannot be established
reliably through culture of urine collected
in a bag (up to 88% of false-positive results,
68% specificity).33-35 The techniques required for catheterization and SPA are well
described.36
Urinalysis cannot substitute for urine
culture to document the presence of UTI
but needs to be used in conjunction with
culture, since urine culture results are not
available for at least 24 hours.
Urinalysis can be performed on any
specimen, including one collected from a
bag applied to the perineum. However, the
specimen must be fresh (<1 hour after voiding with maintenance at room temperature
or <4 hours after voiding with refrigeration), to ensure sensitivity and specificity of
N. of factors present
(girls) (31)
N. of factors present
(circumcised boys) (32)
1%
2%
No more than 2
No more than 3
Risk factors for girls: white race; age <12months; temperature 39C; fever lasting more than 2 days; absence of another source
of infection.
Risk factors for boys: nonblack race; temperature 39C; fever lasting more than 24 hours; absence of another source of
infection.
Adapted from AAP guidelines 2011.29
Nitrite test
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or other proprietary information of the Publisher.
Comments
little value in ruling out UTI (not all urinary pathogens reduce nitrate to nitrite); helpful when positive
(highly specific)
it distinguishes
individuals with asymptomatic bacteriuria (absence
of leukocyte esterase in the urine) from those with
true UTI.
The absence of pyuria in children with true UTIs
is rare
WBCs may be found in the urine during other conditions (eg, streptococcal infections or Kawasaki
disease), and after vigorous exercise.
The key to distinguishing true UTI from asymptomatic bacteriuria is the presence of pyuria.
Microscopy, bacteria
53 (1582)
98 (90100)
83 (6794)
78 (6492)
73 (32100)
81 (4598)
81 (1699)
83 (11100)
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or other proprietary information of the Publisher.
BUONSENSO
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Prophylaxis
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Dosage
(parenteral
treatment)
Dosage
(oral treatment)
Pharmacokinetics 47
Pharmacodnamic 47
Comments 27, 47
Amoxicillinclavulanate
Half-life: 1.5h
Metabolism: hepatic
Excretion: urine
Distribution: widely
distributed (except
CNS)
Trimethoprimsulfamethoxazole
75 mg/kg,
every 24 h
Third-generation
cephalosporin with
broad-spectrum,
Gram- activity;
lower efficacy against
Gram+ organisms;
higher efficacy against
resistant organisms.
Bactericidal activity
results from inhibiting
cell wall synthesis
by binding to one or
more penicillin binding proteins. Exerts
antimicrobial effect by
interfering with synthesis of peptidoglycan, a major structural
component of bacterial cell wall. Bacteria
eventually lyse due to
the ongoing activity
of cell wall autolytic
enzymes while cell
wall assembly is arrested.
150 mg/kg
per d,
divided every
68 h
Half-life: 1-1.5h
Penicillin-binding
Distribution
proteins
Widely throughout the
body
Metabolism: partially
in liver to active metabolite desacetylcefotaxime
Excretion: urine
Metabolism: partial,
hepatic
Excretion: urine
Penicillin-binding
proteins
Cefotaxime
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Ceftriaxone
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.
Ceftazidime
100150 mg/kg
per d,
divided every
8h
Cefixime
8 mg/kg per d in 1
dose
Half-life: 0.8-1.3h
Excretion: unchanged
in urine (80-100%)
Cephalexin
Half-life: 0.8-1.3h
Excretion: unchanged
in urine (80-100%)
(Continue)
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Dosage
(parenteral
treatment)
Dosage
(oral treatment)
Pharmacokinetics 47
Pharmacodnamic 47
Comments 27, 47
10 mg/kg per d in 2
doses
Cefprozil
30 mg/kg per d in 2
doses
Half-life: 1.3h
Absorption: oral 94%
Metabolism: liver
Excretion: urine 61%
unchanged
Half-life: 1-2h
Absorption increased
with food
Metabolism: liver
partially
Excretion: urine 66100% unchanged
7.5 mg/kg
per d,
divided every
8h
Tobramycin
5 mg/kg per d,
divided every
8h
Amikacin
7.5 mg per kg
twice per day
Irreversibly binds to
30S subunit of bacterial ribosomes; blocks
recegnition step in
protein synthesis;
causes growth inhibition. For Gram- bacterial coverage of
infections resistant
to gentamicin and
tobramycin.
Anti-pseudomonal
Broad spectrum of
penicillin plus betabactericidal activity
lactamase inhibitor.
Inhibits biosynthesis
of cell wass mucopeptide and is effective
during stage of active
multiplication
Half-life: 4-6 h
Excretion: urine (2565%), feces (20-40%)
Enzymes inhibited:
hepatic CYP1A2
Inhibits relaxation of
DNA; inhibits DNAgyrase in susceptible
organisms; promotes
breakage of doublestranded DNA
Cefuroxime
axetil
Gentamicin
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Cefpodoxime
Piperacillin tazobactam
29 months of
age: 80 mg of
piperacillin and
10 mg
of tazobactam
per kg three
times per day;
more
than 9 months
of age: 100 mg
of piperacillin
and
12.5 mg of
tazobactam per
kg three times
per day
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or other proprietary information of the Publisher.
BUONSENSO
Ciprofloxacin
150
1020 mg per kg
twice per day
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Adjunctive treatments
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Imaging: VCUG
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Table VI.The NICE algorithm for imaging studies after febrile UTIs.28
Responds well to therapy by 48 h
Not atypical or recurrent UTI
Study
Atypical UTI
History of
prior UTI
Yes
No
No
Yes
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No
No
Only if US is abnormal
1, 2006, to August 31, 2007) and after algorithm use (September 1, 2008, to August
31, 2009). Schroeder et al noted a dramatic
reduction in VCUGs following a febrile UTI
under the selective algorithm from 99%
down to 13% and a lesser but still significant decrease in RBUS (from 99% to 67%).
They demonstrated no significant difference in cases of grades 4 and 5 VUR identified. A reduction in antibiotic prophylaxis
from 27% to 3%, primarily due to lack of
detection of lesser grades of VUR, was not
associated with an increased incidence of
recurrent UTI. The authors concluded that
by restricting urinary tract imaging after
an initial febrile UTI, rates of VCUG and
prophylactic antibiotic use decreased substantially without increasing the risk of UTI
recurrence within 6 months and without
an apparent decrease in detection of highgrade VUR.
This selective approach reduces the
cost and distress associated with the procedure (which necessitates instillation of
a radiopaque, radioactive, or echocontrast
medium into the bladder through urethral
catheterization, followed by serial imaging
during filling and voiding) in children with
an uncomplicated first febrile UTI who are
otherwise well. However, the selective approach may miss a number of children who
have clinically important reflux until another infection occurs.16, 27, 28
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Yes
No
History of
prior UTI
No
Yes
Renal scintigraphy with 99mTc-dimercaptosuccinic acid (DMSA) performed during the acute phase of a UTI, followed by
VCUG if the scintigraphic examination suggests pyelonephritis (once a urine culture is
negative), has been referred to as the top
down approach 65, 66 and focuses on putative pyelonephritis and scarring. This approach may decrease the number of VCUG
examinations performed.
Some expertise recommend renal scintigraphy 6 to 12 months after an acute infection to detect the formation of scarring,
which would require follow-up.61, 67 In
particular, Zaffanello et al.68 prospectively
evaluated children who had experienced
the first febrile UTI at or under the age of 2
years with normal fetal routine ultrasound.
All the children underwent renal ultrasound
after admission; those with sonographic
signs of obstruction were excluded. VCUG
and DMSA scintigraphy were performed
approximately 1 month and 6 months after
the UTI, respectively. VUR was detected in
55.4% of the children and renal scarring in
18.5%. The severity of VUR correlated significantly with renal scarring. The authors
concluded that follow-up renal scintigraphy 6 months after a UTI can predict severe VUR in very young children showing
renal scarring, detecting only those who are
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Pathogens other than E. Coli. P fimbriated E. coli bind to uroepithelial cells and
resist to the normal urine flow. Non fimbriated bacteria ascend the urinary tract with
the help of obstruction or reflux.
In a child with an abnormal US or the
presence of one of the previous risk factors, the Italian Guidelines 50 suggest further
imaging of the urinary tract (cystography)
and the renal parenchyma. In all children
with an abnormal US or in whom VUR has
been shown, a renal cortical scintigraphy
(with DMSA) is recommended 6 months
after the febrile UTI, in order to obtain a
morphologic (presence of UTI related renal
scarring) and functional evaluation (relative
renal function) of the renal parenchyma. In
children with febrile UTI presenting none
of the risk factors discussed above no further imaging of the urinary tract and of the
renal parenchyma is recommended. In case
of recurrence of febrile UTIs, cystography
and renal DMSA scan should be performed.
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According to the new Italian Guidelines,50 if RBUS is normal and no risk factors are present, further imaging is not indicated. If RBUS shows abnormalities or risk
factors are present a complete morphologic
evaluation of the kidney and urinary tract
is indicated.
Suggested risk factors include:
In utero or postnatal US abnormalities: hydronephrosis, ureteral dilatation,
duplicated system, renal hypoplasia, loss
of cortico-medullary differentiation or abnormal parenchymal echogenicity, bladder
wall thickening or irregularity, post-micturating abnormal residual urine volume, bladder diverticula.
Family history of VUR: from a recent
meta-analysis the prevalence of VUR is
27.4% (range 2.9-51.9) in siblings and 35.7%
(range 16.4-61) in offspring screened.
Septicemia: UTI is associated with
sepsis in about 10% of infants. When sepsis
is present the risk of urologic abnormalities
is higher.
Renal failure.
Male infants less than 6 months of
age.
Suspicion of noncompliance of the
family, which requires a more stringent diagnostic approach, in order to avoid dropouts and the loss to follow-up of children
which could be at risk of renal damage.
Micturition abnormalities or thickened
bladder wall which may indicate posterior
urethral valves.
Absence of a clinical response to antibiotics within 72 hours, with persistence
of fever.
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Conclusions
The management of febrile UTIs in children is changing and daily challenging clinicians. A definitive approach cannot be
suggested yet, overall regarding the best
management of children after a first UTI.
On one hand, the concept of primary renal
damage is growing as improved prenatal
ultrasonography has revealed that major
kidney damage in children is frequently related to the presence of hypodysplasia, associated with urologic abnormalities; on the
other hand, infection-related renal scarring
develops in some children, causing further
damage in dysplastic kidneys, with the potential for late effects in previously normal
kidneys.
In our opinion, the new Italian Guidelines 50 and NICE guidelines 28 represents
currently the best approach in the management of UTIs in children, with the only adjunction for NICE guidelines to consider a
renal scintigraphy 6 to 12 months after a
UTI in order to predict severe VUR in very
young children showing renal scarring, de-
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References
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acid scintigraphy instead of voiding cystourethrography for infants with urinary tract infection. J Urol
2004;172:1071-4.
66. Preda I, Jodal U, Sixt R, Stokland E, Hansson S. Normal dimercaptosuccinic acid scintigraphy makes
voiding cystourethrography unnecessary after urinary tract infection. J Pediatr 2007;151:581-4.
67. Stefanidis CJ, Siomou E. Imaging strategies for
vesicoureteral reflux diagnosis. Pediatr Nephrol
2007;22:937-47.
68. Zaffanello M, Cataldi L, Brugnara M, Franchini M,
Bruno C, Fanos V. Hidden high-grade vesicoureteral
reflux is the main risk factor for chronic renal damage in children under the age of two years with
first urinary tract infection. Scand J Urol Nephrol
2009;43:494-500.
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