ARTICLE

Urinary Tract Infections in Children

Melanie C. Marsh, MD,* Guillermo Yepes Junquera, MD,†§ Emily Stonebrook, MD,†¶ John David Spencer, MD,†¶
Joshua R. Watson, MD‡§
*Division of Hospital Medicine, Department of Pediatrics, Advocate Aurora Atrium Health Systems, Chicago, IL
†
Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH
‡
Center for Clinical Excellence, Nationwide Children’s Hospital, Columbus, OH
§
Division of Infectious Diseases and ¶Division of Nephrology and Hypertension, Department of Pediatrics, The Ohio State University College of Medicine,
Columbus, OH

PRACTICE GAP

Recognizing and reducing risk of initial and recurrent urinary tract

infections (UTIs) are important given the disease burden associated with
UTI to patients, families, and the health-care system. Prompt and
accurate UTI diagnosis and thoughtful antibiotic management help
ameliorate antimicrobial resistance. Reducing recurrent UTI risk
includes evaluating a child for factors that augment UTI susceptibility,
such as bowel and bladder dysfunction or anatomic kidney or urinary Drs Spencer and Watson supervised the
tract disorders. drafting and finalizing of the manuscript
and are co–senior authors.

AUTHOR DISCLOSURES: Drs Marsh,

OBJECTIVES After completing this article, readers should be able to: Junquera, Stonebrook, Spencer, and
Watson have disclosed no financial
relationships relevant to this article. This
1. Appropriately diagnose urinary tract infections in children based on
commentary does not contain a
clinical manifestations and laboratory testing. discussion of an unapproved/
investigative use of a commercial
2. Manage urinary tract infections, including optimal antibiotic choice and
product/device. Dr. Marsh receives
duration as well as imaging studies. ongoing research funding for her work
with UTI from the Livewell Grant through
3. Identify and mitigate risk factors for recurrent urinary tract infections. Advocate Aurora Research Institute
(AARI). This grant did not fund any work
directly related to the manuscript.
ABSTRACT
Despite the American Academy of Pediatrics guidelines for the evaluation, ABBREVIATIONS

treatment, and management of urinary tract infections (UTIs), UTI diagnosis AAP American Academy of Pediatrics
and management remains challenging for clinicians. Challenges with acute BBD bowel and bladder dysfunction
CFU colony forming units
UTI management stem from vague presenting signs and symptoms, IBC intracellular bacterial community
diagnostic uncertainty, limitations in laboratory testing, and selecting IV intravenous
KBUS kidney and bladder
appropriate antibiotic therapy in an era with increasing rates of antibiotic-
ultrasonography
resistant uropathogens. Recurrent UTI management remains difficult due QIR quiescent intracellular reservoir
to an incomplete understanding of the factors contributing to UTI, when to TMP-SMX
trimethoprim-sulfamethoxazole
assess a child with repeated infections for kidney and urinary tract anomalies, UPEC uropathogenic Escherichia coli
and limited prevention strategies. To help reduce these uncertainties, this UTI urinary tract infection
VCUG voiding cystourethrogram
review provides a comprehensive overview of UTI epidemiology, risk factors,
VUR vesicoureteral reflux

260 Pediatrics in Review

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 diagnosis, treatment, and prevention strategies that may help pediatricians overcome the challenges associated
with acute and recurrent UTI management.

EPIDEMIOLOGY AND ETIOLOGY bladder), UPEC produce adhesive organelles called type 1 pili
Urinary tract infection (UTI) is a common infection occurring that bind and promote invasion of the superficial bladder ur-
in childhood. In the United States, pediatric UTI accounts for othelium. After internalization, UPEC enter a cytosolic niche
approximately 1.5 million ambulatory visits and 50,000 hospi- called an intracellular bacterial community (IBC). (11)(12)(13)
tal inpatient admissions annually. (1)(2) UTI prevalence varies IBCs develop from a single bacterium and consist of an esti-
by sex, age, and circumcision status. Females account for mated 105 organisms encased in a highly organized matrix.
In the IBC, UPEC develop filaments that extrude from the
80% to 90% of pediatric UTIs overall. (1)(3) Among males,
infected cell. Filamentous UPEC attach to adjacent epithe-
uncircumcised infants experience the highest UTI prevalence.
lial cells, reinvade the urothelium, and create additional IBCs.
(4) An estimated 7% to 8% of females and 1% to 2% of males
(14)(15) To limit infection, the host exfoliates infected bladder
will have at least 1 UTI by age 6 to 7 years. (5)(6)
cells into the urinary stream. After exfoliation, UPEC may in-
UTIs are primarily caused by bacteria, and uropathogenic
vade the underlying basal urothelium and establish a quies-
Escherichia coli (UPEC) is the most common pathogen, ac-
cent intracellular reservoir (QIR). In the absence of bacterial
counting for approximately 80% of UTIs in children. Table 1
replication, QIRs can persist for weeks and are protected
displays the relative frequencies of the 6 most common
from host immune mechanisms and antibiotics. Although
uropathogens encountered among children in a national
the QIR population is small, it is considered a source of re-
surveillance database. (7) Less commonly, other enteric
current cystitis. (15)(16)
gram-negative bacilli such as Citrobacter species and Serratia
To establish pyelonephritis (ie, kidney infection), uropatho-
marcescens are implicated. Among gram-positive bacteria, en-
gens ascend the ureters and invade the kidney. Specifically,
terococci are the most common, but Staphylococcus saprophy-
UPEC bind to epithelial cells in the kidney’s collecting tubules.
ticus should be considered in female adolescents. (8) In
Binding to these kidney epithelia depends on the ability of
addition, group B streptococcus, Staphylococcus aureus, and UPEC to produce type 1 pili or P-pili. After binding to kidney
coagulase-negative staphylococci may be seen in neonates. tubular cells, cytolytic UPEC strains trigger apoptosis, which
(9)(10) Viruses and fungi are less common UTI pathogens facilitates their invasion into the kidney interstitium, promotes
and are briefly discussed at the end of this review. kidney inflammation, and impairs kidney functions. (11)(13)
As pathogens ascend the urinary tract, they encounter me-
UTI PATHOGENESIS chanical and physiologic barriers that limit infection. These
To establish a UTI, uropathogenic bacteria originate from factors include the unidirectional flow of urine, changes in
the enteric and vaginal tracts, spread across the perineum, urine osmolarity and pH, soluble IgA and Tamm-Horsfall
ascend the urethra, and invade the bladder. Our understand- protein, iron-chelating siderophores, and antimicrobial pepti-
ing of UTI pathogenesis has been advanced by studying des. If pathogens invade the bladder urothelium or attach to
UPEC-associated infections in preclinical models and in clin- kidney epithelial cells, they initiate host responses that exfoli-
ical settings. To initiate cystitis (ie, infection restricted to the ate urothelial cells to promote bacterial clearance or engage
pattern recognition receptors, including toll-like receptors, to
Table 1. Most Common Uropathogens among elicit inflammatory chemokines and cytokines that recruit im-
Children from a Large US Surveillance Network mune cells to eradicate bacteria. (17)
URINARY TRACT
INFECTIONS, % RISK FACTORS FOR UTI
ORGANISM FEMALES MALES Although all children are susceptible to UTI, select popula-
Escherichia coli 83 50 tions have increased UTI susceptibility.
Enterococcus species 5 17
Proteus mirabilis 4 11
Klebsiella species 4 10 Young Infants
Pseudomonas aeruginosa 2 7 Neonates and young infants have increased UTI suscepti-
Enterobacter species 1 5 bility because an immature immune system can facilitate
Data from Edlin et al. (7) bacterial colonization and adhesion to the urothelium. In

Vol. 45 No. 5 MAY 2024 261

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 addition, elevated androgen levels in males younger than tract symptoms alone suggests cystitis. In contrast, fever,
6 months may heighten UTI risk. (18) In the first year af- vomiting, or flank pain suggests upper tract involvement,
ter birth, uncircumcised male children are at increased and pyelonephritis is presumed. Infants, preverbal children,
risk for UTI due to increased concentrations of uropatho- and some medically complex youth are unable to report uri-
gens around the external urethral meatus that can potentially nary tract symptoms. In those cases, suspicion for UTI is
colonize the urinary tract and lead to infection. (19)(20) often triggered by a fever without an apparent focus. In ad-
dition, jaundice from direct and/or indirect hyperbilirubine-
Anatomic Disorders of the Urinary Tract mia that is not explained by another etiology may be a clue
Patients with congenital kidney and urinary tract anomalies in some neonates and young infants with UTI, including
or inappropriate bladder emptying are at increased risk for those without fever or other signs of illness. (27)(28)(29)
UTI. Bladder emptying can be impaired by a functional or (30)(31) Many other conditions may present with signs and
anatomic obstruction that occurs with a neurogenic bladder symptoms similar to a UTI, as discussed later herein.
or posterior urethral valves. Impaired bladder drainage facil-
itates urinary stasis and bacterial replication. Moreover, the DIAGNOSIS
need to perform bladder catheterization can heighten UTI Decision to Test
risk. (21) Kidney anomalies such as cystic kidney disease or Given the nonspecific nature of UTI in children, decisions
nephrolithiasis may increase UTI risk. Vesicoureteral reflux around testing must consider risk factors for UTI, number
(VUR) is a UTI risk factor that has been studied extensively. and severity of signs and symptoms, and the presence or
(22) VUR results in urine passing up 1 or both ureters in a absence of a clinically apparent alternative explanation.
retrograde fashion often to the kidneys. The clinical signifi- For febrile children aged 2 to 23 months in whom UTI is
cance of VUR is based on the premise that it predisposes considered, the free, online UTICalc (https://uticalc.pitt.
children to acute pyelonephritis by transporting bacteria edu) is an excellent resource that incorporates demographic
from the bladder to the kidney, which may lead to kidney and clinical information to guide decisions about urine test-
injury. ing (and subsequently, empirical treatment). (32)(33) For
other groups of children, validated decision support tools
Bowel and Bladder Dysfunction are not available, and thus the decision to test is based on
Bowel and bladder dysfunction (BBD) describes a group of clinical suspicion.
lower urinary tract symptoms combined with bowel disor-
ders, including functional constipation, that prevent appro- Urine Testing
priate peristalsis and compromise bladder emptying. (23) Once the decision to test for a UTI is made, collecting a urine
The most common signs and symptoms of BBD in toilet- sample is the next step. Clinicians have several options for
trained children are urinary urgency, withholding maneu- urine collection depending on the age and development of
vers (eg, crossing legs or squatting down to use the heel to the child. To collect a urine sample from infants and young
apply pressure to the perineum), and daytime wetting. (24) children who are incontinent, the American Academy of Pe-
BBD is more common among children with a UTI com- diatrics (AAP) guidelines provide 2 options. (34) Option 1 is
pared with the general population. As a risk factor for recur- to collect urine via catheterization or suprapubic aspiration
rent UTI, BBD disproportionately influences incidence in
children with VUR. Table 2. Clinical Manifestations of Urinary Tract
Infections in Children
Sexual Activity PREVERBAL CHILDREN VERBAL CHILDREN
Sexual activity and the use of spermicides and diaphragms Fever Lower urinary tract symptoms
are also UTI risk factors. Intercourse augments UTI by Poor feeding Dysuria
Vomiting Suprapubic or nonlocalized
facilitating the transfer of uropathogens from the peri- Decreased urine output abdominal pain
neum and genital tract into the urethral meatus. (25)(26) Lethargy Urinary frequency
Irritability Urgency
Jaundice Enuresis
CLINICAL MANIFESTATIONS Hematuria
Upper urinary tract symptoms
Children with a UTI may present with a variety of signs and Fever
symptoms, which may be affected by age and development Vomiting
Flank pain
(Table 2). In verbal children, the presence of lower urinary

262 Pediatrics in Review

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 for urinalysis and culture. Option 2 is to collect urine by non- standard urinalysis but requires additional time and exper-
invasive means (eg, urine bag) for urinalysis; if the results tise compared with standard urinalysis. (44) Urine Gram-
show pyuria, nitrite, or bacteriuria, then a second sample ob- stain is particularly helpful when the child has received
tained via catheterization or suprapubic aspiration must be antibiotics before obtaining urine for culture.
obtained for urinalysis and culture. One emergency depart- In febrile children aged 2 to 24 months, the AAP guide-
ment showed that by implementing option 2, many children lines define UTI as both a urinalysis suggesting infection
avoided an invasive procedure without prolonging length of (pyuria or bacteriuria) and a urine culture that yields at least
stay. (35) Importantly, urine samples collected via bag should 50,000 colony forming units (CFU)/mL of a uropathogen.
not be used for culture because of higher rates of contamina- (34) In toilet-trained children, a UTI diagnosis is made in
tion. (36)(37) Likewise, urine collected via cotton balls in neo- the presence of urinary signs and symptoms, urinalysis sug-
nates should not be cultured. In toilet-trained children, a gesting infection, and positive urine culture. A threshold of
mid-stream, clean-catch method is recommended. 50,000 or 100,000 CFU/mL is typically used to define sig-
nificant bacteriuria from clean-catch specimens.
Making the Diagnosis
Hallmarks of a UTI are pyuria, urinary nitrite, and bacteri- Uncertainties in Diagnosis
uria. (34)(38) Pyuria is defined by urine microscopy with Several factors make the diagnosis of UTI challenging.
at least 5 white blood cells (WBCs) per high-power field First, UTI signs and symptoms can be nondescript and
from centrifuged urine or at least 10 WBC/mm3 from overlap with other clinical conditions. A meta-analysis of
noncentrifuged urine, or detection of leukocyte esterase studies examining signs and symptoms of pediatric UTI
(as a surrogate marker for pyuria) on urine dipstick analy- found that among preverbal children, fever (temperature
sis. Nitrite is detected when bacteria capable of reducing >102.2 F [>39 C] and especially >104 F [>40 C]), fever
urinary nitrate to nitrite have incubated in the urine for at duration longer than 24 hours, and suprapubic tenderness
least 4 hours. (39) Enteric gram-negative bacteria, Pseudo- increased the probability of UTI, whereas vomiting, diarrhea,
monas, and some staphylococcal species reduce nitrate, poor feeding, and irritability were of little diagnostic value.
whereas streptococci and enterococci do not. Significant (45) Among verbal children, abdominal pain, back pain, dys-
bacteriuria may be demonstrated on urine microscopy and uria, frequency, and new-onset enuresis were helpful, whereas
ultimately confirmed by growth of a uropathogen in urine offensive urine odor had no effect on UTI probability. The ab-
culture. In many ambulatory settings, urine microscopy is sence of any individual symptom was insufficient to exclude a
not available at the point of care, precluding an immediate UTI.
assessment for WBCs or bacteria. Second, pyuria may be caused by many conditions other
Many studies have evaluated the test characteristics of than UTI, including urethritis, vulvovaginitis, sexually trans-
urinalysis (dipstick and/or microscopy) for diagnosing UTI, mitted infections, appendicitis, other acute febrile illnesses,
or more accurately, for predicting a positive urine culture. crystalluria or nephrolithiasis, intrinsic kidney disease, and
Sensitivity and specificity depend on the population tested others. (46) The common scenario of a symptomatic child
(age, sex, comorbidities), urine collection method, urinalysis whose urine dipstick is positive for leukocyte esterase but
method used, threshold for positivity of the urinalysis com- negative for nitrite leads to diagnostic uncertainty.
ponent, and definition of a positive urine culture. Summary Third, diagnosing UTI in the absence of pyuria is the sub-
data from 3 meta-analyses and 1 large study are shown in ject of debate. The AAP guidelines emphasize the necessity
Table 3. (40)(41)(42)(43) Enhanced urinalysis, which con- of pyuria, stating that pyuria is the key to distinguishing true
sists of a urine Gram-stain plus hemocytometer WBC UTI from asymptomatic bacteriuria or culture contamination
count from uncentrifuged urine, performs better than in young, febrile children. (38) Despite historical concerns

Table 3. Summary of Urinalysis Test Characteristics

TEST SENSITIVITY, % SPECIFICITY, % +LR –LR
Leukocyte esterase 72–83 78–87 3.8–6.1 0.20–0.34
Nitrite 40–53 97–98 15.7–26.5 0.48–0.61
Urine white blood cells 67–85 79–89 3.2–5.3 0.20–0.42

1LR5positive likelihood ratio, LR5negative likelihood ratio.

Data derived from Downs et al, (40) Gorelick and Shaw, (41) Kazi et al, (42) and Williams et al. (43).

Vol. 45 No. 5 MAY 2024 263

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 that young infants up to 2 to 3 months old do not reliably bacteriuria is unnecessary. (60) In addition, culture reports
demonstrate pyuria, recent studies showed high sensitivity of should differentiate between contaminants and typical uro-
pyuria in this age group. (9)(47) However, some experts have pathogens. Finally, identification and testing of isolates
challenged the inclusion of pyuria in the definition of UTI should not be automatically reported when more than 2
based on a meta-analysis showing the point prevalence of unique bacterial isolates are present in culture. Implemen-
asymptomatic bacteriuria to be less than 0.5% and a study tation of strategies such as these may guide clinicians in
showing that pyuria was absent in 13% of symptomatic chil- not only UTI diagnosis but also appropriate treatment.
dren with positive urine culture results. (38)(48)(49) In addi-
tion, compared with UPEC, non–E coli pathogens are less MANAGEMENT
likely to result in pyuria. (49)
Decision to Treat Empirically versus Wait for Culture
Fourth, the definition of a positive urine culture is un-
During the past 3 decades, E coli have developed mecha-
clear. The AAP guidelines’ threshold of 50,000 CFU/mL
nisms to evade the bactericidal mechanisms of antibiotics
from catheterized specimens is based on the cutoff point
routinely prescribed to treat UTIs, such as b-lactams, fluo-
above which most cultures yield a single uropathogen
roquinolones, and aminoglycosides. Up to 90% of E coli
rather than contaminants. (50) However, some studies sug-
strains are now resistant to at least 1 unique antibiotic,
gest that the culture threshold defining UTI should be
and E coli infections now account for half the estimated
lower than 50,000 CFU/mL. (51)(52) The AAP guidelines
global burden of antibiotic resistance. Antibiotic overuse
point out reasons for low colony counts in some patients
and misuse have accelerated the prevalence of antibiotic
(eg, short incubation time in the bladder in infants) and
resistance among UPEC. (61)
describes the culture threshold as “operational and not
Because it takes approximately 24 hours to receive ini-
absolute.” (34) In febrile infants with pyuria, cultures
tial urine culture results, clinical signs and symptoms and
yielding at least 10,000 CFU/mL may be indicative of a
urinalysis results are often used to make a presumptive di-
UTI. (53)
agnosis of UTI. Studies have shown that among children
Fifth, distinguishing between cystitis and pyelonephritis
diagnosed as having a UTI based on symptoms and uri-
is not clear-cut. When upper urinary tract signs or symptoms
nalysis results, almost half have a resultant negative urine
are present (Table 2), clinicians typically presume that the
culture. (62)(63) If a child with suspected cystitis is well-
patient has pyelonephritis for subsequent management deci-
appearing and does not have fever or other signs of sys-
sions. Fever is considered an upper urinary tract symptom
because studies have shown that most children with a febrile temic illness, it is reasonable to wait for the culture result
UTI have evidence of pyelonephritis on technetium-99m before initiating antibiotic therapy. This is particularly per-
dimercaptosuccinic acid scan, the previous gold standard im- tinent in the current climate of antibiotic overuse and may
aging modality for pyelonephritis that is no longer in clinical curtail emerging antimicrobial resistance. (64) However, it
use. (54)(55) In addition, serum inflammatory markers have is important that reliable follow-up is available, which may
not proved to be of sufficient diagnostic value for pyelone- include having the patient’s or guardian’s contact informa-
phritis. (56) tion, identifying the primary care provider, or establishing
Finally, although beyond the scope of this review, assess- outpatient follow-up in their medical home.
ment of symptoms and test results is even more challenging In children with suspected UTI associated with fever or
in children with immunocompromise or anatomic disorders other upper urinary tract symptoms, prompt empirical an-
of the urinary tract. Pyuria is often absent in febrile neutro- tibiotic should be provided while awaiting culture results.
penic children with a UTI. (57) Children with neurogenic Prolonged fever before initiation of antibiotic therapy may
bladders are at increased for UTI but also have high rates of increase risk of kidney scar formation. (65)(66) Although
asymptomatic pyuria and bacteriuria. (58)(59) Standard crite- previously this relationship has been controversial and po-
ria to optimally identify those with true infection are lacking. tentially confounded by age, recurrent UTI, ethnicity, or
To minimize diagnostic uncertainty, an expert panel on BBD, there does seem to be an association when control-
diagnostic stewardship for UTI recently recommended ling for these factors. (66) Risk of scar increases most
that ideal reporting of urine culture results should inform steeply after 48 to 72 hours of delay from fever onset to
clinicians that colony counts greater than 100,000 CFU/mL antibiotic initiation. However, 1 study found that for every
may not represent a true infection in the absence of symp- hour that antibiotics were delayed, the odds of new scar-
toms and that treatment for mixed flora or asymptomatic ring increased by 0.8%. (66)

264 Pediatrics in Review

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 Empirical Antibiotics empirical antibiotic for UTI, but resistance among UPEC has
When considering empirical therapy for UTI treatment, it increased over time and exceeds 20% in many areas of the
is important to review local antibiogram data (ie, antibiotic United States. (7) Ciprofloxacin is not a wise antibiotic choice
susceptibility patterns) for common uropathogens, as well for most children. Similar to TMP-SMX, ciprofloxacin resis-
as any previous urine culture and susceptibility data spe- tance is increasing. (7) Furthermore, given concerns regard-
cific to the child if there is a history of UTI. (38) Given the ing its adverse effects, ciprofloxacin should be reserved for
predominance of UPEC, even in children without nitrite treatment of infections for which no reasonable oral alterna-
on urinalysis, it is probably unnecessary to cover for En- tive exists. (70) In addition, children who are receiving pro-
terococcus species empirically. (67) There are several rea- phylactic antibiotics may have increased risk of resistant
sonable oral empirical antibiotic options. Nitrofurantoin is organisms, and previous urine cultures should be reviewed
a targeted UTI antibiotic that is an excellent empirical when choosing antimicrobial coverage in this population.
choice for treating cystitis in adolescents, where the mono- (71)(72)
hydrate/macrocrystal formulation may be given via a cap- For those unable to tolerate enteral agents, IV and intra-
sule twice daily. However, nitrofurantoin oral suspension muscular options can be considered. If a child is otherwise
for younger children is a less attractive option given poor stable to be discharged home, a single dose of intramuscular
palatability, the 6-hour dosing interval, and higher cost. ceftriaxone 50 mg/kg may be given, followed by an oral anti-
Furthermore, nitrofurantoin should not be used to treat biotic prescription and close outpatient follow-up. Although
suspected pyelonephritis because it does not achieve ade- there are no clear-cut guidelines on when children require
quate serum or kidney tissue concentrations. Cephalexin hospital admission for the monitoring and treatment of
is another narrow-spectrum antibiotic with high UPEC a UTI, factors for consideration are listed in Table 4. For
susceptibility in many geographic locations. If local anti- children hospitalized for IV treatment, appropriate op-
biogram data are favorable, cephalexin may be given for tions include cefazolin, ceftriaxone, or dual therapy with
children with cystitis or pyelonephritis, at appropriate ampicillin plus gentamicin. Cefazolin is preferred as a
doses for the indication. (68) narrow-spectrum empirical option if local susceptibility
Other empirical options suggested in AAP guidelines in- patterns are favorable.
clude amoxicillin-clavulanate, oral third-generation cephalo-
sporins, and trimethoprim-sulfamethoxazole (TMP-SMX). Definitive Antibiotic Treatment
Amoxicillin alone is usually a poor choice for empirical treat- Once urine culture and susceptibility data are available, antibi-
ment because of high rates of UPEC resistance, but it may be otic treatment should be tailored to the most narrow-spectrum
used for definitive treatment if appropriate based on culture agent effective for the infection. In hospitalized children, tran-
and susceptibility results. Although oral third-generation ceph- sition from IV to oral antibiotics should be considered as
alosporins (cefdinir, cefixime, cefpodoxime) do have a role in soon as children are tolerating medications and fluids
UTI treatment, they are broader in spectrum and have less fa- by mouth. Oral antibiotics are equally as efficacious as
vorable pharmacokinetic properties compared with cepha- IV antibiotics in most children. (73)(74) An approach to
lexin. (69) In addition, clinicians sometimes erroneously guide clinicians on antibiotic administration includes
assume that susceptibility of urine isolates to intravenous (IV) “cascade reporting” of antibiotic susceptibility. When
third-generation cephalosporins (ceftriaxone, cefotaxime) pre- antibiotic susceptibility testing is finalized in a positive
dicts susceptibility to oral third-generation agents, but this is urine culture, the cascade reporting preferentially lists anti-
not reliably true. TMP-SMX was previously a commonly used biotics recommended by the local antimicrobial stewardship

Table 4. Indications for Hospitalization of Children with a Urinary Tract Infection

CATEGORY INDICATIONS
Social and demographic factors Age #28 d
Unreliable access to follow-up
Clinical severity factors Systemic illness concerning for sepsis
Intractable pain
Inadequate response or symptom progression despite appropriate enteral antibiotic therapy
Concern for urinary tract obstruction or kidney dysfunction requiring intervention or close monitoring
Treatment factors Inability to retain enteral antibiotic (eg, frequent vomiting)
Infection with a multidrug-resistant organism for which an effective enteral antibiotic is unavailable

Vol. 45 No. 5 MAY 2024 265

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 program or national societies. This strategy promotes anti-
microbial stewardship and may reduce antibiotic misuse or Recurrent UTI
overuse. (60)

Test for structural

Duration of Treatment Screen for voiding Conspaon
kidney and urinary
disorders evaluaon
For cystitis, national US guidelines for treatment duration tract disorders
are lacking, but an antibiotic course of 3 to 4 days seems
Kidney and bladder
to be equivalent to longer courses and is endorsed by mul- Increase hydraon ultrasound +/-
Timed voiding and Fiber Voiding
tiple international organizations. (75)(76)(77)(78)(79) For cystourethrogram*
febrile UTI/pyelonephritis, courses as short as 7 days are
Stool soeners Consider anbioc
supported by comparative effectiveness data and are con- Ancholinergics and Osmoc
prophylaxis with high-
grade VUR +/- structural
sistent with AAP guidelines. (34)(80) The recently pub- laxaves kidney disease

lished Short-Course Therapy for Urinary Tract Infections

Counseling and
in Children (SCOUT) randomized clinical trial evaluated Referral to
Behavior
Referral to
Pediatric Urology Pediatric Urology+
5-day versus 10-day treatment durations for children 2 modificaons
months to 10 years old meeting strict UTI criteria, 38%
Figure. Suggested management for children with repeated urinary tract
of whom were febrile at presentation (94% of those aged infections (UTIs). Stepwise investigation and screening strategies are out-
2–23 months). (81) For the primary outcome of treatment lined in the orange boxes, and management strategies are shown in the
blue boxes. *A voiding cystourethrogram should be considered if kidney
failure (occurrence of UTI at or before the day 11–14 fol- and bladder ultrasonography shows evidence of uroepithelial thickening,
low-up visit), short-course treatment failed noninferiority hydronephrosis, or hydroureter. 1A referral to pediatric urology should be
considered for a child with high-grade vesicoureteral reflux (VUR), uretero-
criteria. However, the low rates of treatment failure over- cele, bladder diverticulum, solitary kidney, horseshoe kidney, kidney size
all (4.2% in the short-course group) were encouraging, discrepancy greater than 1 cm, kidney cysts, or kidney scarring. Adapted
from Khan et al. (83)
and 67 children would need to be treated with the longer
duration to prevent 1 febrile UTI. A favorable response to Voiding Cystourethrogram
treatment is indicated by improvement, and ultimately Historical AAP guidelines recommended a voiding cystour-
resolution, of symptoms. Obtaining a urine culture after ethrogram (VCUG) for all children aged 2 to 24 months af-
completing antibiotic therapy as a proof of cure is not ter their first febrile UTI to accurately identify VUR. Studies
recommended. (82) after these guidelines were published showed that less than
30% of children undergoing VCUG had VUR and only 10%
KIDNEY AND URINARY TRACT IMAGING of those had dilating VUR. (84)(85) As a result, the AAP
Kidney and Bladder Ultrasonography guidelines were amended and now recommend a VCUG
AAP guidelines recommend kidney and bladder ultrasonog- after a febrile UTI in children 2 to 24 months old with an
raphy (KBUS) in all infants aged 2 to 24 months with a fe- abnormal KBUS, atypical uropathogens or clinical course,
brile UTI. (34) In most cases, the KBUS may be performed known kidney scarring, or family history of structural kidney
after the acute UTI process has resolved to minimize tran- disease. (34) VCUG should also be obtained, even in the set-
sient findings caused by inflammation. Early imaging is rec- ting of normal KBUS, if a child has recurrent UTI given the
ommended to evaluate for a kidney/perinephric abscess or limited sensitivity of KBUS to detect VUR as noted previ-
obstructive uropathy if the course is unusually severe or clin- ously herein (Fig).
ical improvement does not occur after 48 hours of appropri-
ate antibiotic therapy. The goal of KBUS is to evaluate for UTI PREVENTION
urinary tract anomalies such as obstruction, nephrolithiasis, Antibiotics should be used sparingly for UTI prevention. A
abdominal mass, or structural kidney anomalies. Although major concern of using long-term antibiotic prophylaxis for
findings such as ureteral dilation and hydronephrosis may prevention of recurrent UTI is the development of antibiotic
suggest VUR, it is not a sensitive imaging modality for VUR resistance. (86)(87) In the Randomized Intervention for Chil-
diagnosis. (54) KBUS should also be considered in older chil- dren with Vesicoureteral Reflux (RIVUR) study, 76% of re-
dren with recurrent UTIs, non–E coli pathogens, unusually current UTIs in children receiving TMP-SMX prophylaxis
severe presentations, and acute kidney injury, and in male were due to antibiotic-resistant pathogens compared with
patients (Fig). 28% in the placebo group. (88) Although the RIVUR study

266 Pediatrics in Review

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 demonstrated a 50% reduction in recurrent UTI for those Cranberry-based products are popular, with the active
receiving daily TMP-SMX prophylaxis, this equates to ingredient proanthocyanidin preventing UPEC adhesion
8 children with VUR being treated with antibiotic pro- to bladder epithelial cells or reducing the formation of bac-
phylaxis for a single child to benefit. (89) Furthermore, terial biofilms. Pediatric clinical trials suggest that cran-
these results have not been consistent in other studies or berry products modestly reduce the incidence of UTI in
in systematic reviews and meta-analyses. (89)(90) Thus, youth with normal urinary tract anatomy. A review of 8 trials
pediatricians should be highly selective in terms of which using cranberry juice or cranberry extract for UTI prevention
patient populations to place on daily antibiotic prophy- concluded that 4 trials had a reduced incidence of UTI with
laxis. Before doing so, they should also consider address- cranberry-based therapy. (96) However, definitive conclu-
ing other variables that can promote UTI (Fig). sions cannot be made from these trials about the utility of
cranberry products in UTI prevention given their differences
Bowel and Bladder Dysfunction in cranberry formulations and dosing. Larger, well-designed
Clinicians can use standardized questionnaires for diag- trials are needed. The value of cranberry in UTI prevention
nosing BBD in a primary care setting. These include the has recently been reviewed. (97)
Dysfunctional Voiding Scoring System and the Vancouver Probiotics comprising Lactobacillus species also show prom-
Symptom Score for Dysfunctional Elimination Syndrome, ise in UTI prevention. Probiotics boost endogenous immune
which can be accessed online or in the following references. defenses, scavenge nutrients needed by bacteria for replica-
(91)(92) Both surveys quantitatively and qualitatively assess tion, reduce pH to suppress uropathogen growth, and prevent
constipation, daytime and nighttime wetting, urinary ur- UPEC binding to urothelial cells. (61)(98)(99) During the past
gency, and difficulty in voiding or stooling. If a child with 2 decades, several studies have tested the effects of probiotics
UTI is suspected of having BBD, pediatricians can recom- on UTI prevention with or without antibiotics. (100)(101)(102)
mend a voiding and stooling diary to document frequency of Given the mixed outcomes in these studies, the utility of pro-
voiding and defecation, volume voided, incontinence, stool biotics for UTI prevention in children is unclear.
characteristics, and fluid intake. An objective measurement of D-mannose is a monosaccharide that competitively in-
stool can be made using the modified Bristol stool chart for hibits UPEC binding to urothelial cells. Given promising
children, available online or in the following reference. (93) preclinical data, synthetic mannosides are now being devel-
BBD treatment can include managing constipation with oped and tested. (103) To date, there are few clinical studies
hydration, increased fiber intake, and stool softeners. If there of D-mannose in pediatric UTI prevention. Thus, we can
is concern for withholding urine or an overactive bladder only speculate about the benefits of D-mannose from adult
contributing to UTI, these conditions can be managed with data that show efficacy. However, given the variations in
biofeedback or behavioral modifications such as timed void- design among different studies, the clinical benefits of
ing (voiding on schedule every 2–3 hours). (23) Oxybutynin, D-mannose remain unclear. (97)(104)(105)
an anticholinergic agent, can be used in children with an Vaccinations are also being developed to prevent UTI.
overactive bladder. (94) Referral to a pediatric urology prac- Four vaccines have recently shown promise in randomized
tice for evaluation or treatment of voiding disorders may also controlled trials. The immunogens on which these vaccines
be considered (Fig). (83) are based include whole cell heat-killed bacteria, bacterial cell
wall components, nutrient acquisition proteins, and proteins
Antibiotic-Conserving Approaches to Prevent UTI facilitating bacterial adhesion. (106)(107)(108)
Due to rising antibiotic resistance rates, antibiotic-sparing
options to prevent UTI are needed. There are several ap- Surgical Approaches to Prevent UTI
proaches that have been investigated, but none of them are Male circumcision decreases UTI risk, specifically among
recommended as front-line approaches to prevent UTI. The neonates, and the AAP supports the benefits of circumcision
role of hydration in preventing UTI has been tested in sev- for UTI risk reduction. (19)(109) In older children, high-grade
eral small, historical observational studies. Findings from or dilating VUR surgical correction can reduce UTI suscepti-
these studies have recently been summarized in a system- bility. Clinical trials comparing medical versus surgical man-
atic review in adults and children. (95) However, because of agement for recurrent UTI show comparable decreases in
mixed methods and results of the included studies, drawing UTI incidence and kidney scarring. (110)(111) Thus, surgery is
firm conclusions about the role of hydration in UTI preven- reserved for children whose VUR is unlikely to spontaneously
tion is not possible. resolve, those with higher risk for pyelonephritis, a history of

Vol. 45 No. 5 MAY 2024 267

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 kidney scarring, or impaired kidney function. Surgical correc-
age). The tool calculates pre-test and post-test
tion is not recommended for children with low-grade VUR
probabilities of UTI and guides decisions regarding
given the high likelihood of spontaneous resolution and low
whether to test and empirically treat for UTI.
risk of kidney scarring. (83)
(Based on strong research evidence) (32)(33)

VIRAL AND FUNGAL UTI • A UTI is best defined by the presence of symptoms
with inflammation evidenced by pyuria and a urine
Adenovirus can cause UTIs in immunocompetent hosts,
culture with at least 50,000 colony-forming units
including urethritis, hemorrhagic cystitis, and nephritis.
per milliliter of a uropathogen. However, challenges
Treatment is supportive. In hematopoietic stem cell recipi-
surrounding UTI diagnosis include signs and
ents, adenovirus, BK virus, and cytomegalovirus can cause
symptoms that are nonspecific, debate around the
hemorrhagic cystitis. In kidney transplant recipients, BK
necessity of pyuria, and uncertainty regarding the
virus reactivation is associated with nephropathy. Manage-
optimal culture threshold to define significant
ment of these infections in immunocompromised hosts is
bacteriuria. (Based on some research evidence as
often multifaceted and beyond the scope of this review.
well as consensus) (34)(38)(53)
(112)(113) When Candida is isolated in urine culture, it may
indicate a UTI or colonization. In asymptomatic patients • Cephalexin and nitrofurantoin are recommended
with an indwelling bladder catheter, removal of the catheter empirical oral antibiotic choices for UTI (if supported
without antifungal therapy is typically sufficient. (114) However, by local antibiotic susceptibility data), usually for 3
for patients who are very-low-birthweight infants, neutropenic, to 4 days for uncomplicated cystitis and 7 days for
or undergoing a urologic procedure, treatment of asymptom- febrile UTI/pyelonephritis. (Based on some research
atic candiduria is recommended. Those with symptoms sug- evidence as well as consensus) (75)(80)
gesting cystitis or pyelonephritis may also be treated, and • After a first febrile UTI in an infant or young child,
fluconazole is the drug of choice for susceptible organisms. clinicians should obtain kidney and bladder
Additional evaluation and management recommendations ultrasonography (KBUS) to evaluate for urinary
for UTI due to Candida in specific patient populations are tract anomalies. A voiding cystourethrogram is
provided in national guidelines. (114) indicated if the KBUS is abnormal or if the child
experiences a second febrile UTI. (Based on some
CONCLUSIONS research evidence as well as consensus) (34)
UTI continues to challenge pediatric medical providers. • Clinicians should strive to identify and mitigate
Prompt and accurate diagnosis is important to minimize modifiable risk factors for UTI and recurrence,
UTI symptoms, reduce UTI-associated sequelae, and mini- including bowel and bladder dysfunction (BBD).
mize the inappropriate use of antibiotics. With a better Assessment for BBD via validated questionnaires,
understanding of the etiology, pathogenesis, diagnosis, initiation of behavior interventions, and treatment
and treatment of UTI, clinicians will be better prepared to of constipation can begin in the medical home,
manage this common clinical infection. with referral to specialists in cases refractory to
initial interventions. (Based on some research
Summary evidence as well as consensus) (23)(24)

• Uropathogenic Escherichia coli is the most common

cause of urinary tract infection (UTI), followed by
other enteric gram-negative bacilli and Enterococcus
species. (Based on strong research evidence) (7) Take the quiz! Scan this QR code to take the quiz,
access the references and teaching slides, and
• UTICalc is an excellent decision support tool that view and save images and tables
clinicians may use when considering a UTI in a (available on May 1, 2024).
febrile infant or young child (2–23 months of

268 Pediatrics in Review

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 PIR QUIZ

1. A 4-month-old previously healthy girl is brought to the office by her parents

with a 2-day history of fever that spiked to 102.4 F (39.1 C) today. The
parents gave her ibuprofen, which improved her temperature. She has been
mildly fussy with mildly decreased breastfeeding. She has not had vomiting
or diarrhea. On physical examination, she is alert and smiling at her mother.
There is no clear focus of infection on examination. A bag urine specimen
for urinalysis resulted with 21 leukocyte esterase and negative nitrite. Which
one of the following is the most appropriate next step in management?
A. Begin oral amoxicillin therapy.
B. Bladder catheterization to send urine for culture. REQUIREMENTS: Learners can
take Pediatrics in Review quizzes
C. Culture the urine from the bag specimen. and claim credit online only at:
D. Intramuscular ceftriaxone. http://pedsinreview.org.
E. Schedule renal bladder ultrasonography for tomorrow.
To successfully complete 2024
2. A 2-month-old boy is brought to the office by his parents after a recent Pediatrics in Review articles for
hospitalization of a first-time febrile urinary tract infection (UTI). He was AMA PRA Category 1 Credit™,
discharged to home 5 days ago on oral amoxicillin as the urine culture grew learners must demonstrate a
ampicillin-susceptible Escherichia coli. Mom states that he is doing well and minimum performance level of
60% or higher on this
is back to his normal self. He is uncircumcised, and his parents are opposed
assessment. If you score less
to having him circumcised. Renal bladder ultrasonography noted mild left- than 60% on the assessment,
sided hydronephrosis, and a voiding cystourethrogram (VCUG) showed you will be given additional
grade II vesicoureteral reflux on the left. Which one of the following is the opportunities to answer
most appropriate recommendation to prevent renal scarring with questions until an overall 60%
or greater score is achieved.
subsequent UTI(s)?
A. Advise that he be brought in to be seen for any febrile illness and This journal-based CME activity
receive early empirical antimicrobial treatment if evaluation findings are is available through Dec. 31,
2026, however, credit will be
consistent with a UTI.
recorded in the year in which
B. Begin amoxicillin antimicrobial prophylaxis for 12 months. the learner completes the quiz.
C. Begin azithromycin antimicrobial prophylaxis alternating with amoxicillin
antimicrobial prophylaxis every 2 months.
D. Begin oral oxybutynin.
E. Schedule for surgical repair of the vesicoureteral reflux.
3. A previously healthy 14-month-old girl is brought to the emergency
department (ED) with a 1-day history of fever with the maximum 2024 Pediatrics in Review is
approved for a total of 30
temperature being 102.5 F (39.1 C) last night. Her appetite is mildly
Maintenance of Certification
decreased but she seems to be having a normal number of wet diapers. She (MOC) Part 2 credits by the
has not had vomiting. She has no known allergies. She is alert and her American Board of Pediatrics
physical examination is negative for any clear source of infection. A (ABP) through the AAP MOC
catheterized urine specimen showed 31 leukocyte esterase, positive nitrites, Portfolio Program. Pediatrics in
Review subscribers can claim up
and 20 to 30 white blood cells per mm3 on an unspun specimen. Culture is
to 30 ABP MOC Part 2 points
pending. Which one of the following is the most appropriate therapy? upon passing 30 quizzes (and
A. Admit to the hospital for intravenous (IV) vancomycin and gentamicin. claiming full credit for each
quiz) per year. Subscribers can
B. Admit to the hospital for observation pending the urine culture result.
start claiming MOC credits as
C. Begin oral amoxicillin therapy. early as October 2024. To learn
D. Begin oral cephalexin therapy. how to claim MOC points, go
E. Begin oral nitrofurantoin therapy. to: https://publications.aap.org/
journals/pages/moc-credit.

Vol. 45 No. 5 MAY 2024 269

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user
 4. A previously healthy 6-week-old girl is admitted to the hospital with fever
for approximately 30 hours. She was brought to the ED due to a
temperature of 104 F (40 C). She has had decreased oral intake and
1 episode of vomiting. On physical examination she is ill-appearing, but
there are no focal findings. A lumbar puncture was performed, and
cerebrospinal fluid studies were normal. Catheterized urine was obtained,
and urinalysis resulted positive nitrites, 11 leukocyte esterase, and negative
results for blood, protein, and glucose. The microscopic urine noted
15 white blood cells per mm3 on unspun urine. She was started on IV
ceftriaxone in the ED, which has been continued. The urine grew E coli
susceptible to ceftriaxone and ampicillin and resistant to trimethoprim-
sulfamethoxazole. Blood and cerebrospinal fluid cultures have no growth at
3 days. Renal bladder ultrasonography performed today is normal. She is
now eating well and appears well. Which one of the following is the most
appropriate next step in management?
A. Change to oral amoxicillin to complete a 7-day course of treatment.
B. Change to oral amoxicillin-clavulanate to complete a 10-day course of
treatment.
C. Continue IV ceftriaxone to complete a 7-day course.
D. Change to IV ampicillin to complete a 10-day course.
E. Obtain aVCUG.
5. A 4-month-old girl is admitted to the hospital for a second febrile UTI. Her
history is remarkable for hospitalization for a febrile E coli UTI at 2 months of
age. Renal bladder ultrasonography with the first UTI was normal. Urine
culture with the current UTI is growing extended-spectrum b-lactamase
Klebsiella oxytoca. She is currently receiving IV meropenem and is now
afebrile after 48 hours of treatment. Which one of the following is the most
appropriate next step in management?
A. Add IV ceftaroline.
B. Computed tomography of the abdomen and pelvis.
C. Dimercaptosuccinic acid renal scan.
D. Magnetic resonance imaging of the abdomen and pelvis.
E. VCUG.

270 Pediatrics in Review

Downloaded from /pediatricsinreview/issue/45/5

by HINARI BAND 1 user