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Peds 2020012138
Peds 2020012138
Urinary tract infection (UTI) is common in children, and girls are at abstract
a significantly higher risk, as compared to boys, except in early infancy. Most
cases are caused by Escherichia coli. Collection of an uncontaminated urine
specimen is essential for accurate diagnosis. Oral antibiotic therapy for 7 to
10 days is adequate for uncomplicated cases that respond well to the
treatment. A renal ultrasound examination is advised in all young children
with first febrile UTI and in older children with recurrent UTI. Most children
with first febrile UTI do not need a voiding cystourethrogram; it may be
considered after the first UTI in children with abnormal renal and bladder
a
ultrasound examination or a UTI caused by atypical pathogen, complex Division of Pediatric Nephrology, Departments of Pediatrics
and Urology, Wayne State University School of Medicine and
clinical course, or known renal scarring. Long-term antibiotic prophylaxis is Wayne Pediatrics, Detroit, Michigan; bDepartment of
used selectively in high-risk patients. Few patients diagnosed with Pediatrics, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania; and cDepartment of Urology,
vesicoureteral reflux after a UTI need surgical correction. The most Boston Children’s Hospital and Department of Surgery,
consequential long-term complication of acute pyelonephritis is renal Harvard Medical School, Harvard University, Boston,
Massachusetts
scarring, which may increase the risk of hypertension or chronic kidney
disease later in life. Treatment of acute pyelonephritis with an appropriate Dr Mattoo conceptualized and formatted the
antibiotic within 48 hours of fever onset and prevention of recurrent UTI manuscript template, drafted the initial manuscript,
and reviewed and revised the manuscript; Drs
lowers the risk of renal scarring. Pathogens causing UTI are increasingly Nelson and Shaikh participated in formatting the
becoming resistant to commonly used antibiotics, and their indiscriminate initial manuscript, drafted sections of the initial
use in doubtful cases of UTI must be discouraged. manuscript, and reviewed and revised the
manuscript; and all authors approved the final
manuscript as submitted and agree to be
accountable for all aspects of the work.
DOI: https://doi.org/10.1542/peds.2020-012138
Urinary tract infection (UTI) is one of common organisms include Klebsiella,
the most common bacterial infections Proteus, Enterococcus, and Enterobacter Accepted for publication Sep 4, 2020
in childhood. In the first year of life, it is species.9–11 Organisms such as Address correspondence to Tej K. Mattoo, MD, Wayne
more common in boys (3.7%), as Pseudomonas, group B Streptococcus, Pediatrics, 400 Mack Ave, Suite 1 East, Detroit, MI
48201. E-mail: tmattoo@med.wayne.edu
compared to girls, (2%) and after and Staphylococcus aureus are usually
infancy, it is significantly more associated with CAKUT, genitourinary PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
prevalent in girls. During prepubertal surgery, a foreign body (eg, catheter),
age, the incidence in girls is 3%, as or recent antibiotic treatment, whereas Copyright © 2021 by the American Academy of
Pediatrics
compared to 1% in boys.1–3 The risk of infection with urea-splitting organisms
UTI recurrence in the first 6 to (eg, Proteus) is associated with stone FINANCIAL DISCLOSURE: The authors have indicated
they have no financial relationships relevant to this
12 months after the initial UTI is ∼12% formation.8,12 Prompt diagnosis and article to disclose.
to 30%.4,5 Besides sex, other significant treatment are important for the
FUNDING: No external funding.
risk factors for UTI are bladder-bowel prevention of acute complications as
dysfunction (BBD); congenital well as renal scarring. In the last 2 POTENTIAL CONFLICT OF INTEREST: The authors have
indicated they have no potential conflicts of interest
anomalies of kidneys and the urinary decades, a significant amount of to disclose.
tract (CAKUT), including vesicoureteral research has been done on UTI in
reflux (VUR); and the circumcision children, particularly on renal imaging
To cite: Mattoo TK, Shaikh N, Nelson CP.
status in young boys.4,6–8 and long-term antibiotic prophylaxis Contemporary Management of Urinary Tract
Approximately 85% to 90% of UTIs are after UTI. The objective of this review is Infection in Children. Pediatrics. 2021;147(2):
caused by Escherichia coli. Other to summarize the current literature on e2020012138
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female sex (or uncircumcised boy), researchers have indicated potential and the voided midstream urine is
maximum temperature .39°C, and the roles for polymorphisms of the caught in a sterile cup.48 Regardless
absence of another source for fever. angiotensin-converting enzyme and of the technique, contamination of
The calculator was validated in transforming growth factor b1 voided specimens from infants is
a cohort of .2000 children and was genes.43 In studies of plasminogen a significant concern, particularly for
found to reduce unnecessary testing, activator inhibitor 1, researchers girls and uncircumcised, young boys.
decrease missed UTIs, and reduce found that it was not associated with In older, toilet-trained children,
treatment delays. Bubble baths may risk of renal scarring among infants a urine specimen can be obtained by
infrequently cause irritation and after first febrile UTI.44 catching the midstream urine in
discomfort of the genital mucosa and a sterile cup after cleaning of skin
periurethral tissue in children,27 which around the genital area; girls may
may be wrongly interpreted as a UTI: DIAGNOSIS OF UTI benefit from facing backward on the
there is little evidence that the bubble toilet, which splays the legs and labia
A targeted history and physical
baths actually cause UTI.28 and may reduce contamination from
examination and positive urinary
skin and vaginal surfaces. In
findings are essential for an accurate
uncircumcised boys, gentle
RISK FACTORS FOR RENAL SCARRING diagnosis of UTI.
retraction of the prepuce (if possible)
A number of risk factors are • History and physical examination: is important to obtain an
associated with acquired renal In older, verbal children, important uncontaminated specimen, and urine
scarring due to APN. These include findings include dysuria, urgency from boys with significant phimosis
a high grade of VUR (grades .2 and and/or frequency, abdominal or is likely to be contaminated.
particularly grades 4 and 5),7,29 flank pain, and new-onset
• Urinalysis: Antibiotic treatment of
duration of fever of .72 hours before incontinence.45 In contrast, signs
UTI is often started empirically
antibiotic initiation,30–32 recurrent and symptoms of UTI in infancy are
because urine culture results take 1
UTI,29,33–35 and organisms other than nonspecific, and fever may be the
to 2 days. The leukocyte esterase
E coli.36–38 Previously, a young age was only symptom, although neonates
test on urine dipstick is the most
considered to be a risk factor, but may present with hypothermia.
widely available screening test. The
recent studies have revealed that older History of constipation, UTI in
results are usually reported
children may be at higher risk of renal siblings or parents, and recent
semiquantitatively (negative, trace,
scarring29,36,39; the discrepancy may infections or antibiotic treatment
11, 21, and 31). The accuracy of
be related to the inadvertent inclusion should be ascertained. Relevant
currently available screenings tests
of patients with preexisting congenital signs on abdominal examination
for UTI is summarized in Table 2.49
scarring (renal dysplasia) in the include distention, presence of
The table also demonstrates that
earlier studies because differentiation a mass or palpable stool, flank or
the currently available bedside
between congenital and acquired suprapubic tenderness, and/or
tests have a high rate of false-
scarring after APN is challenging, a palpable bladder, particularly after
positive and negative results with
particularly when baseline (ie, pre- voiding.
treatment implications. A
UTI) studies are not available. In • Urine specimen: In non–toilet- microscopic urinalysis has only
comparison with the other pathogens, trained children, urine collection marginally better accuracy than the
infection with P fimbriae E coli method has a profound significance dipstick. Until better and more
increases the probability of ascending for diagnosis of UTI. Urine specimen accurate biomarkers for UTI
infection but does not appear to be in such children should be collected become available, the limitation of
associated with increased preferably by ureteral bedside UTI screening should be
dimercaptosuccinic acid (DMSA) renal catheterization or suprapubic kept in mind and used only in
scan abnormalities.40 It has long bladder aspiration, particularly if conjunction with clinical
been speculated that there is a specimen collected by perineal bag assessment. Blood and/or protein
a genetic predisposition in some is dipstick-positive. In a recent video on urine dipstick examination are
children to develop renal scarring published in the New England poor indicators of UTI.
after APN. Polymorphisms of the Journal of Medicine, researchers
• Urine culture: The acceptable
HSPA1B gene of HSP72 protein were reviewed the methods of suprapubic
colony count threshold for a urine
found to be associated with renal aspiration.46 Another reasonable
culture positive for UTI depends on
scarring,41 whereas variants of the alternative is the Quick-Wee method
its collection method. It is
toll-like receptor 4 gene were of urine collection.47 In this method,
50 000 colony-forming units
associated with renal scarring in the suprapubic area is stimulated by
(CFUs)/mL for samples obtained by
another study.42 In other studies, using a gauze soaked in cold fluid,
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Furthermore, unlike APN that needs injury may occur because of lower among children whose
second- or third-generation dehydration or an administration of treatment started within 24 hours of
cephalosporin for at least 1 week, a nonsteroidal anti-inflammatory onset of fever, compared with those
uncomplicated (nonfebrile) bacterial drug, such as ibuprofen. Nonsteroidal whose treatment started after
cystitis generally responds well to the anti-inflammatory drugs may also 72 hours of fever.32
short duration (3–5 days) of first- diminish renal function by causing
generation cephalosporin, papillary necrosis or interstitial
RENAL IMAGING AFTER UTI
trimethoprim-sulfamethoxazole, or nephritis. The latter can also be
nitrofurantoin.66–69 The utility of caused by the antibiotic that is being Renal imaging after UTI is driven
currently available screening tests used for UTI treatment. Urosepsis primarily by a need to rule out an
(C-reactive protein, procalcitonin, and may occur, particularly with Gram- underlying renal or urinary tract
erythrocyte sedimentation rate) is negative infections. anomaly or the assessment of renal
limited. The evidence suggests that an injury.
increased serum C-reactive protein or The most consequential long-term
complication of APN is renal scarring. Renal Bladder Ultrasound
procalcitonin level is suggestive of
APN.20 The erythrocyte The reported prevalence of renal The purpose of renal bladder
sedimentation rate does not appear scarring after febrile UTI is ∼15%39 ultrasound (RBUS) is to evaluate for
useful in diagnosing APN. Some other and ranges from 3% after the first urinary tract anomalies, including
features that may be helpful in UTI to 29% after .3 febrile UTIs.36,70 obstruction, renal structural
differentiating cystitis from APN are In the Randomized Intervention for anomalies, nephrolithiasis or
shown in Table 3.66–69 Children with Vesicoureteral Reflux calcification, or an abdominal mass.
(RIVUR) trial, only ∼7% of children RBUS is a less sensitive imaging
developed new scarring during the modality for the diagnosis of VUR,75
COMPLICATIONS OF UTI study period, and this was primarily and normal RBUS does not rule out
Acute complications of UTI are among children with grade 4 VUR.29 high-grade VUR. Particular findings
similar to those associated with any In most children, renal scarring may on RBUS that may indicate a higher
febrile illness in a young child. These not be clinically significant,71–73 but it probability of VUR include ureteral
include dehydration, electrolyte may cause hypertension and dilation, renal parenchymal changes,
abnormalities, and febrile seizures. proteinuria and a progressive decline and bladder abnormalities. RBUS
Renal complications of APN are in renal function in those with cannot be used to accurately diagnose
uncommon in otherwise healthy bilateral significant scarring.74 patients with APN or renal
children but may include renal Delayed initiation of antibiotic scarring.76–78 The 2011 AAP
abscess or complete occlusion of treatment is associated with guidelines recommend RBUS be
a preexisting, partial ureteropelvic increased risk of scarring, with the performed in all infants (2–24
junction obstruction. Acute kidney odds of new renal scarring 74% months) with febrile UTI.34 Older
children with recurrent UTIs may also
benefit from an RBUS. The RBUS can
TABLE 3 Features That May Be Helpful in Differentiating Cystitis From APN
be deferred until after resolution of
Characteristic APN Uncomplicated Cystitis
the UTI but should be considered
Age distribution More common in younger Typically in children aged .2 y during the acute episode if the illness
children
seems unusually severe or if high
Fever130 .38°C Afebrile or low-grade fever #38°C
Recent viral NA Viral cystitis fevers persist beyond 48 to 72 hours
illness131 of treatment34; such atypical course
Systemic symptoms Common Uncommon suggests complications, such as renal
Local symptoms Flank pain and/or tenderness Dysuria, urgency, frequency, urinary abscess or occult obstruction, that are
incontinence, suprapubic pain, and/or
well-seen on RBUS. A deferred RBUS
hematuria
Causative agent Bacterial (E coli is the Bacterial (E coli is the commonest), viral, permits more accurate interpretation
commonest) fungal, and chemical of the anatomy, without potential for
Urinary findings false-positive findings associated with
Gross hematuria Uncommon May have fresh blood and clots131,132 tissue edema or endotoxin-induced
Urine culture for Positive Negative results in viral, fungal, and chemical
dilation.
bacteria cystitis
RBUS Normal or may reveal edema Normal or may reveal thickened urinary
and hyperemia of kidney bladder wall, debris in the bladder
Voiding Cystourethrogram
Renal complication Renal scarring None In the last decade, the practice
NA, not applicable. patterns have dramatically shifted,
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American Urological Association were at highest risk for renal scarring • Avoiding or deferring the use of
recommends continuous antibiotic (odds ratio 24.2, 95% confidence antibiotic in a patient suspected of
prophylaxis in children aged interval 3.0–197), as compared to having viral or chemical cystitis;
,1 year and a selective approach in most adherent patients.115 It also • Not using a routine, long-term
older children based on patient age, revealed that the long-term antimicrobial prophylaxis in low-
severity of VUR, recurrence of UTI, prophylaxis with trimethoprim- risk patients; and
presence of BBD, and renal cortical sulfamethoxazole was not associated
• Not treating ABU with antibiotics.
anomalies.111 The European with an increased risk of skin and soft-
Association of Urology, European tissue infections, pharyngitis or
Society of Pediatric Urology, and sinopulmonary infections,116 or SURGICAL INTERVENTION FOR VUR
Swedish and Italian Society of excessive weight gain.117 In another Few patients diagnosed with VUR after
Pediatric Nephrology also study, researchers reported that UTI need surgical correction. It is
recommend a more selective routine monitoring of blood chemistry, usually reserved for patients with high-
approach based on a combination of renal function, or complete blood cell grade VUR, recurrent UTI despite
patient age, severity of VUR, and count were not necessary in children antibiotic prophylaxis, and
renal scarring.112–114 Other factors receiving long-term trimethoprim- noncompliance with or intolerance of
that should be considered before sulfamethoxazole prophylaxis.118 prophylactic antibiotics and for the
initiating long-term antimicrobial Regarding the cost-effectiveness of worsening of renal scars.127 Open
prophylaxis include the status of antibiotic prophylaxis, one study ureteral reimplantation remains the
toilet training, risk of antibiotic revealed that the prophylaxis was mainstay of surgical correction for
resistance, anticipated compliance associated with marginally higher VUR, although endoscopic treatment is
with daily medication costs, as compared with placebo,119 also widely used, particularly for
administration, parental choice, and whereas researchers in another study lower-grade VUR. Laparoscopic
the medication expense. In all reported that the prophylaxis was reimplantation techniques (with or
recommendations, younger age is more cost-effective than observation without robotic assistance) have
a particular consideration for in children with high-grade (grade 4) increased in recent years, but use
prophylaxis because of a nonspecific but not low-grade VUR; this finding remains limited to specific centers.
clinical presentation for UTI, the should be considered in light of the Endoscopic treatment involves
difficulty in getting urine specimens, fact that the large majority of children subureteral or intraureteral injection of
the higher possibility of a need for with VUR do not have high-grade a bulking agent (most commonly
hospitalization for intravenous disease.120 dextranomer and hyaluronic acid
antibiotic administration and [Deflux]). The decision for timing and
Antibiotic resistance of pathogens
hydration, an increased risk of the type of intervention is based on the
causing UTI at any age is a growing
septicemia, and family disruption
concern internationally.121–125 As age of the patient, status of the kidneys,
and parental anxiety. In some cases, grade of VUR, and parental wishes.6
such, there is a need for a judicious
a preemptive antimicrobial
use of antibiotics for the prevention
prophylaxis may be necessary to
and the treatment of UTIs. Some of PREVENTION OF RECURRENT UTI
lower the risk of first UTI, such as in
the measures that could help
those with high-grade VUR Recurrent UTI can be prevented by
reduce the risk of antibiotic
diagnosed during workup for preventing constipation and
resistance in children with UTIs are
antenatal hydronephrosis. The avoidance of urine withholding
as follows126 :
duration of prophylaxis depends on behavior in toilet-trained children.
multiple factors and may range from • Collection of uncontaminated urine Although increased oral fluid helps
a few days until a VCUG can be specimen for diagnosis so that flush bacteria from the bladder,
obtained in those recently patients do not receive an antibiotic prompts frequent urination, and
diagnosed with UTI to a few years for a false-positive urine culture alleviates constipation, there is
for children with VUR on medical result; limited evidence that it is effective in
management. • Initiation of empirical antibiotic preventing UTIs.128 In uncircumcised
therapy only after collecting an boys, gentle, daily retraction and
Secondary analysis of the RIVUR study uncontaminated urine specimen to cleaning should be performed; in
has revealed that the patients who help with the selection of a right boys with phimosis, topical
took trimethoprim-sulfamethoxazole antibiotic for continued treatment corticosteroid ointment or
,70% of the time were 2.5 times or its discontinuation, depending circumcision may be necessary to
more likely (95% confidence interval on the urine culture results and the prevent UTI recurrence. There is no
1.1–5.6) to have a recurrent UTI and patient’s clinical status; evidence in children to recommend
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