2. INTRODUCTION
Urinary tract infection (UTI) is a common and important clinical
problem in childhood.
Although children with pyelonephritis tend to present with fever, it is
difficult on clinical grounds to distinguish cystitis from
pyelonephritis, particularly in young children (< 2 years).
Upper UTIs (ie, acute pyelonephritis) may lead to renal scarring,
hypertension, and ESRD.
3. Prevalence:
In young children (< 2 years) with fever:
• The overall prevalence of UTI is approx 7 %
• It is highest among uncircumcised boys, particularly < 3 months.
• White children have a 2-4 fold higher prevalence than do black children.
• Girls have a 2-4 fold higher prevalence than do circumcised boys.
• White girls with a Temp ≥39°C have a UTI prevalence of 16%.
In older children: the prevalence of UTI was 7.8%.
4. MICROBIOLOGY:
Gram-negative bacterial pathogens
• E. coli is the most common bacterial cause of UTI (80 % of UTI).
• Others: Klebsiella, Proteus, Enterobacter, and Citrobacter.
• Infection with an organism other than E. coli is associated with a higher likelihood of renal scarring.
Gram-positive bacterial pathogens
• Staphylococcus saprophyticus, Enterococcus, rarely, S. aureus.
Viruses.
• are uncommon causes of UTI in children
• usually limited to the lower urinary tract
Fungi
• uncommon
• Risk factors: Immunosuppression and long-term use of broad-spectrum antibiotic, and indwelling urinary
catheter
5. PATHOGENESIS:
most UTI beyond the N.B period are the result of ascending
infection.
Colonization of the periurethral area by uropathogenic enteric
pathogens is the first step in the development of a UTI.
Pathogens attach to the uroepithelial cells via an active process
mediated by glycosphingolipid receptors on the surface of
epithelial cells. Bacterial attachment recruits toll-like receptors
(TLR). TLR binding triggers a cytokine response, which
generates a local inflammatory response.
6. PATHOGENESIS : VIRULENCE
FACTORS
A variety of virulence factors enable bacteria to ascend
into the bladder and kidney.
The best-studied virulence factors in E. coli are pili.
Bacteria possessing pili can adhere effectively to the
uroepithelium and ascend into the kidney, even in
children without VUR.
In the kidney, the bacterial inoculum generates an
intense inflammatory response, which may ultimately
lead to renal scarring.
7. • Age: highest in boys < 1 year and girls < 4 years.
• Lack of circumcision: 4-8 fold higher prevalence of UTI
• Female infants: 2-4 fold higher prevalence of UTI
• Race/ethnicity: white children > black children.
• Genetic factors
• Urinary obstruction:
• Anatomic conditions, Neurologic conditions, Functional conditions
• Suspect when: voiding problems, family hx of urologic abnormalities,
patient with GU abnormalities or when symptoms do not respond to
appropriate therapy.
• Bladder and bowel dysfunction
• Vesicoureteral reflux
• Sexual activity
• Bladder catheterization
HOST FACTORS:
8. BACTERIAL-HOST INTERACTIONS:
There is indirect evidence that alteration of the
normal periurethral flora promotes attachment
of pathogenic bacteria
Circumcision
Use of antibiotics
9. General risk factors:
• Recurrent febrile UTI
• Delay in treatment of acute
infection
• Bladder and bowel dysfunction
• UT Obstructive malformations:
• VUR
Predictors of renal scarring
after first UTI:
• VUR (high-grade)
• Abnormal renal bladder US
• Elevated inflammatory
markers: CRP of >40 mg/L or
PMNs >60 %
• Temperature ≥39°C
• organisms other than E. coli
12. Younger children
• nonspecific symptoms and signs
• History of UTI
• Temperature >40°C or > 24 hours
• Suprapubic tenderness
• Lack of circumcision
• Other symptoms: conjugated
hyperbilirubinemia, irritability, poor
feeding, or FTT
Older children:
• fever
• urinary symptoms
• abdominal pain
• fever, chills, flank pain
(pyelonephritis)
• short stature, poor weight gain, or
hypertension
• Suprapubic tenderness
• costovertebral angle tenderness
13. History Physical exam Investigations
Prompt recognition and treatment of UTI is an important factor in the
prevention of renal scarring.
14. Hx of acute illness
• fever
• urinary symptoms
• abdominal pain, suprapubic discomfort, back pain,
• vomiting
• recent illnesses, antibiotics administered
The PMHx should include risk factors for UTI:
• Chronic urinary symptoms
• Chronic constipation
• Previous UTI or previous undiagnosed febrile illnesses
• VUR
• Family hx of frequent UTI, VUR, and other genitourinary abnormalities
• Antenatally diagnosed renal abnormality
• chronic sequelae of UTI: Poor growth, Elevated blood pressure
15. Physical examination
VS: BP and Temp
Growth parameters:
poor weight gain, FTT
(chronic or recurrent
UTI)
Abdominal exam:
• suprapubic tenderness
• Abdominal mass (enlarged
bladder or enlarged kidney)
• costovertebral tenderness
Examination of the
external genitalia for
• anatomic abnormalities
• and signs of vulvovaginitis,
vaginal foreign body,
Evaluation of the
lower back for signs of
occult
myelomeningocele
Evaluation for other
sources of fever
16. LABORATORY EVALUATION
The laboratory evaluation for the child with suspected UTI
includes
obtaining a urine sample for
a dipstick and/or microscopic evaluation
and urine culture.
Pyuria and significant bacteriuria on urine culture are necessary
to make the diagnosis.
17.
18.
19.
20. How to obtain
Catheterization
or suprapubic
aspiration is
the preferred
method of
urine collection
in infants and
young children
who are not
toilet-trained.
A clean-voided
specimen is the
preferred
method of
collection in
toilet-trained
children.
All urine
specimens
should be
examined as
soon as
possible after
collection.
Urine obtained
in a sterile
bag not be
used for
culture.
21. Dipstick analysis
• 88 % sensitive
• Leukocyte esterase: Positive result is
suggestive of UTI.
• Nitrite: positive test is suggestive of
UTI.
• highly specific, with a low false-
positive rate.
Microscopic exam
• Standard microscopy
• urine is examined for WBCs and
bacteria.
• Pyuria: ≥5 WBC/hpf
• Bacteriuria: presence of any
bacteria/hpf.
• sensitivity is at best 81 %,
• ●Enhanced urinalysis
• pyuria : ≥10 WBC/mm3
• Bacteriuria: any bacteria per 10 oil
immersion fields of a Gram-stained
smear.
22. Urine culture:
the standard test for the diagnosis of UTI.
should be performed for all children in whom UTI is a diagnostic consideration
Catheterization or suprapubic aspiration is the preferred in infants and children who are not toilet-
trained.
A clean-voided specimen is preferred in toilet-trained children.
Urine obtained for culture should be processed as soon as possible after collection.
23. Are not particularly helpful in the diagnosis of UTI and are
not routinely necessary in children with suspected UTI
Other laboratory tests
Markers of
inflammation
Serum
creatinine
Blood culture
Lumbar
puncture
24.
25. DIAGNOSIS OF UTI
UTI is best defined as significant bacteriuria in a patient with pyuria.
If the urine culture demonstrates significant growth
of Enterococcus, Klebsiella, or Pseudomonas aeruginosa in a child
with symptoms of UTI, UTI may be diagnosed in the absence of pyuria
26. Significant bacteriuria
depends upon the method of collection and the identification of the isolated organism.
Clean voided sample:
• significant bacteriuria is growth of ≥100, 000 CFU/mL of a single uropathogen;
• a second uropathogen with growth <50,000 CFU/mL is permitted,
Catheter sample
• significant bacteriuria is growth of ≥50,000 CFU/mL of a single uropathogen
• a second uropathogen with growth <10,000 CFU/mL is permitted,
• children who have growth of 10,000 to 50,000 CFU/mL should have a repeat urine culture.
• It is considered sig. if the 2nd culture grows ≥10,000 CFU/mL and pyuria is present on urinalysis.
●Suprapubic sample
• significant bacteriuria is growth of any uropathogenic bacteria
• (the growth of one colony on the plate is equivalent to 1000 CFU/mL).
Lactobacillus spp, coagulase-negative staphylococci, and Corynebacterium spp are not considered clinically
relevant uropathogens
27. The AAP UTI guideline, published in 2011 and reaffirmed in
2016, recommends both pyuria and 50,000 CFU/mL be present
in febrile infants
The criterion of ≥50000 CFU/mL remains the current standard,
but clinicians may want to consider ≥10,000 CFU/mL in
catheterized specimens from young infants at risk for UTI and
have both fever and pyuria.
In 2012, the Italian Society of Pediatric Nephrology issued
guidelines recommending the threshold be ≥10,000 CFU/mL
for specimens collected by catheterization.
28. False negatives
A bacteriostatic
antimicrobial agent is
present in the urine
Rapid rate of urine
flow with reduced
incubation time
Obstruction of the
ureter
In such cases, Renal scintigraphy may be helpful
29. Pyuria is not specific for UTI.
Pyuria is absent in approx 10 % of children with UTI
• Early in the course of UTI
• Colonization (eg, asymptomatic bacteriuria)
• With certain uropathogens
(Enterococcus species, Klebsiella species, P. aeruginosa)
If the urine culture demonstrates significant growth of Enterococcus, Klebsiella, or
P. aeruginosa in a child with symptoms of UTI, UTI may be diagnosed in the
absence of pyuria.
30. In children who are suspected of having UTI based on a positive
culture, but in whom pyuria is not detected urinalysis, repeating
the urinalysis and urine culture can help to distinguish between
early infection and colonization
Presence of Pyuria
and bacteriuria:
UTI
The absence of
pyuria and
bacteriuria:
bacterial
contamination of the
initial sample
Bacteriuria without
pyuria:
asymptomatic
bacteriuria
31. DIFFERENTIAL DIAGNOSIS
Asymptomatic bacteriuria
• colonization of the urinary tract with bacteria in
the absence of inflammation
• occurs in 1 to 3 % of infants and preschool-age
children, and 1 % of older children.
• in most children, it resolves spontaneously
without causing renal scarring/renal dysfunction
• antibiotic treatment is not recommended.
Other considerations
• DDx depends upon the presenting symptoms
and signs.
• well-appearing infant with fever without focus:
UTI and occult bacteremia.
• urinary symptoms and bacteriuria may be
caused by nonspecific vulvovaginitis, irritant
urethritis, urinary calculi, urethritis secondary to
a STDs, and vaginal foreign body.
• Patients with group A streptococcal infection,
appendicitis, and Kawasaki disease may present
with fever, abdominal pain, and pyuria.
• Bowel and bladder.
33. Elimination of infection and prevention of urosepsis
Relief of acute symptoms
Prevention of recurrence and long-term complications:
• hypertension,
• renal scarring,
• Impaired renal growth and function
34. Management
Acute management
antimicrobial therapy to
treat the acute infection
evaluation for possible
predisposing factors
(eg, urologic
abnormalities).
Long-term
management
prevention of recurrence
and complications
35. Inpatients or outpatient?
Usual indications for hospitalization
• Age <2 months
• Clinical urosepsis
• Immunocompromised patient
• Vomiting or inability to tolerate oral medication
• Lack of adequate outpatient follow-up
• Failure to respond to outpatient therapy
Most infants older than two months with UTI can be safely managed
as outpatients
36. ANTIBIOTIC THERAPY
Antimicrobial
therapy for
children with
presumed
UTI depends
upon a
number of
factors,
including:
• the age of the child, severity of illness,
• presence of vomiting,
• duration of fever,
• underlying medical and/or urologic
problems,
• the antimicrobial resistance patterns in
the community.
37. • Early and aggressive antibiotic therapy (eg, within 72 hours of
presentation) is necessary to prevent renal damage.
• Empiric antimicrobial therapy should be initiated immediately after
appropriate urine collection in children with suspected UTI and a
positive urinalysis. Especially for children who are at increased risk
for renal scarring, including those with:
Fever (especially
>39°C or >48
hours)
Ill appearance
Costovertebral
angle
tenderness
Known immune
deficiency
Known urologic
abnormality
38. A Gram-stained smear of the urine, can help guide
decisions regarding empiric therapy.
The ultimate choice of antimicrobial therapy is based
upon the susceptibilities of the organism isolated.
Escherichia coli accounts for 80% of UTI in children.
Empiric therapy for UTI in infants and children should
provide adequate coverage for E. coli.
39. • For E. coli:
• Approx 50 % are resistant to amoxicillin or ampicillin.
• Resistance to 1st-generation cephalosporins, Augmentin
or ampicillin-sulbactam, and TMP-SMX have been reported.
• Risk factors for resistance to narrow-spectrum antibiotics include
• lack of circumcision in boys,
• bowel and bladder dysfunction,
• receipt of antibiotics in the previous 6 months
• Hispanic ethnicity
40. • 3rd-generation cephalosporins and aminoglycosides are appropriate
1st-line agents for UTI in children.
• When Enterococcal UTI is suspected
• Those with a urinary catheter, instrumentation of the urinary tract, or
an anatomical abnormality),
• amoxicillin or ampicillin should be added.
41. Oral therapy
Most children > 2 months of age who are not vomiting
can be treated with oral antimicrobials
cephalosporin are the first-line oral agent in the
treatment of UTI in children w/o GU abnormalities.
Oral amoxicillin-clavulanate also was shown to be
effective
42. Oral therapy
First UTI > 1 episode of UTI
1st or 2nd generation
cephalosporins
Amoxicillin clavulanic acid
In a child with Beta lactam
allergy,
• TMP-SMX, or ciprofloxacin is a
reasonable strategy.
Check the previous culture
result
Cefixime
2nd generation
cephalosporins
Trimethoprim
sulfamethoxazole
43. Fluoroquinolones (eg, ciprofloxacin) are effective for E. coli.
Use only for UTI caused by Pseudomonas aeruginosa or other MDR gram-
negative bacteria.
Oral agents that are excreted in the urine but do not achieve
therapeutic serum concentrations (eg, nalidixic acid, nitrofurantoin)
should not be used to treat UTI in febrile infants and young children in
whom renal involvement is likely
44. Cephalosporins and aminoglycosides are appropriate
first-line parenteral agents for empiric treatment of
UTI in children.
Definitive therapy is based upon the results of urine
culture and sensitivities.
Ampicillin should be included if enterococcal UTI is
suspected.
Parenteral antibiotics should be continued until the
patient is clinically improved (eg, afebrile) and able to
tolerate oral liquids and medications
45. parenteral antibiotics
Ampicillin
(100 mg/kg/day in
4 doses)
Gentamicin
(7.5 mg/kg/day IV
in 3 doses)
Ceftriaxone
(50 to
75 mg/kg/day)
Cefotaxime
(150 mg/kg/day in
3-4 doses)
Gentamicin
Beta lactam
allergy
46. Outpatient parenteral therapy
• Once-daily parenteral administration of gentamicin
or ceftriaxone
• Candidates:
• age ≥3 months,
• unable to tolerate oral therapy
• nontoxic appearing
• well hydrated
• without urologic abnormalities,
47. • Patients who have recently been treated with antibiotics are
more likely to have a uropathogen that is resistant to that agent
• pending culture and susceptibility results, they may require an
antibiotic from a different class.
Recent antibiotic exposure
• Review of the antimicrobial susceptibilities of the most recent
urinary pathogens can be helpful in choosing empiric therapy for
children with recurrent UTI.
Recurrent UTI
48. short-course antimicrobial therapy (2-4 days) is effective as
standard duration (7 - 14 days) therapy in eradicating bacteria
in children with suspected lower UTI (afebrile)
short-course therapy may enable clinicians to limit the duration
of exposure to antimicrobials, reducing the likelihood of
adverse events and the emergence of bacterial resistance
49. longer course of therapy is used for febrile children (usually 10 days)
and a
short course of therapy (3-5 days) is used for immune-competent
children presenting without fever.
Oral antibiotics can be used to complete the course of therapy for
patients who are initially treated with parenteral antibiotics.
•When the patient is tolerating oral fluids and has been afebrile for 24 hours.
•There is no minimum duration for parenteral therapy
50. The clinical condition of most patients improves within 24 - 48
hours of initiation of appropriate antimicrobial therapy
The mean time to resolution of fever is 24 hours, but fever may
persist beyond 48 hours
In children whose clinical condition worsens or fails to improve
as expected within 48 hours of initiation of antimicrobial
therapy,
Broadening antimicrobial therapy may be indicated
Renal and bladder ultrasonography should be performed ASAP (renal
abscess or surgically correctable anatomic abnormalities or
obstruction)
51. Repeat urine cultures after
48 hours of therapy if
the patient fails to respond clinically
or the uropathogen is not
susceptible to the antibiotic that is
being used for treatment.
• for children who had the
expected clinical response
and the uropathogen is
susceptible to the antibiotic
that is used.
• it is not necessary to repeat
urine cultures during
antimicrobial therapy to
document sterilization of the
urine.
52. Decisions regarding prophylactic antibiotics for children
following initial febrile UTI should be made on a case-by-
case basis.
The 2011 AAP practice guideline does not recommend
prophylactic antimicrobials following the first febrile UTI in
children 2 to 24 months.
The United Kingdom's NICE guideline for UTI in children
indicates that antibiotic prophylaxis should not be
routinely recommended in infants and children following
their first UTI but may be warranted after recurrent UTI.
53. ADJUNCTIVE THERAPIES
Dexamethasone
decreased urinary levels of
interleukin-6 and interleukin-8 in
children,
Possible prevention of scar
formation.
• Additional studies are
necessary to confirm these
results and to determine the
optimum glucocorticoid
regimen before adjunctive
glucocorticoids are routinely
recommended in the
treatment of UTI in children.
54. If such abnormalities are detected, steps can be taken to modify the
risk of subsequent renal damage
surgical intervention antibiotic prophylaxis
to identify abnormalities of the GUT that require additional
evaluation or management (eg, obstructive uropathies, dilating VUR).
55. Ultrasonography:
RBUS can be used to evaluate
• the size and shape of the kidneys,
• the presence of duplication and dilatation of the ureters,
• and the existence of gross anatomic abnormalities.
• renal or perirenal abscess or pyonephrosis
The major advantages of RBUS are
• lack of exposure to radiation,
• Noninvasive
• Helpfulness in predicting risk of renal scarring
56. Children < 2 years of age with
a first febrile UTI
Children of any age with
recurrent febrile UTIs
Children of any age with a
UTI who have a family history
of renal or urologic disease,
poor growth, or hypertension
Children who do not respond
as expected to appropriate
antimicrobial therapy
57. The American Academy of
Pediatrics (AAP)
• recommends RBUS for all
infants and children 2 to
24 months following
their first febrile UTI.
The United Kingdom's
NICE guideline on UTI in
children
• recommends RBUS for
infants < 6 months and
for children > 6 months
who have atypical or
recurrent UTI.
58. Renal US Timing
When RBUS should be performed depends upon the clinical situation.
Aim: to identify complications (eg, renal/
perirenal abscess, pyonephrosis).
ASAP during the acute phase
In infants and young
children with
unusually severe
illness
failure to improve as
expected after
initiation of therapy,
Aim: to reduce the risk of false positive
results
after the acute phase.
For infants and young children who respond as
expected to appropriate antimicrobial therapy,
59. VCUG is the test of choice to establish the
presence and degree of VUR
VUR is an important risk factor for renal
scarring.
(25 - 30 % of children < 18 years with a 1st UTI
have VUR)
VCUG is expensive, invasive, has radiation
exposure and may miss a significant
portion of children who are at risk for renal
60. VCUG is indicated for:
• Children of any age with ≥ 2 febrile
UTIs
• Children of any age with a 1st
febrile UTI and:
• Any anomalies on RBUS
• The combination of Temp ≥39°C
and a pathogen other than E. coli
• Poor growth or hypertension
watchful waiting (observe, do VCUG
with recurrence)
• For children with a 1st febrile UTI
and without
• abnormalities on RBUS
• Temp ≥39°C + a pathogen other
than E. coli
• poor growth
• Hypertension
61. It remains uncertain whether the benefits of detection and treatment
of VUR after the first UTI outweigh the risks.
The uncertainty centers on the changing view of the role of VUR in
the development of renal damage and progressive kidney disease and
the lack of clarity regarding the effectiveness of medical or surgical
management of VUR in reducing the risk of renal scarring.
Although the risk of renal scarring is increased in children with VUR
compared with children without VUR and increases with increasing
grades of VUR, VUR is neither necessary nor sufficient for the
development of renal scars
62. • recommends postponing VCUG until the 2nd febrile UTI in children 2 - 24
months of age unless there are atypical or complex clinical circumstances or the
RBUS reveals hydronephrosis, scarring, or other findings suggestive of high-
grade VUR or obstructive uropathy
The 2011 AAP clinical practice guideline (reaffirmed in 2016)
• Infants <6 months with atypical or recurrent UTI
• children 6 months – 3 years with atypical or recurrent UTI and dilation on RBUS,
poor urine flow, non-E. coli infection, or family history of VUR.
The United Kingdom's NICE guideline suggests VCUG for
63. AlthoughVCUG is often scheduled several weeks after
UTI, it may be performed ASA the patient is
asymptomatic.
Early imaging (as early as the 1st week) does not appear
to falsely increase the detection ofVUR.
To avoid the use of prophylactic antibiotics in children
w/oVUR, recommendation is to doVCUGs
during the last days of antimicrobial therapy
or immediately after completion of antimicrobial
therapy for UTI.
65. RENAL SCINTIGRAPHY
Renal scintigraphy using (DMSA scan) can be used to detect acute
pyelonephritis and renal scarring.
The role of DMSA scan in the management of acute UTI is
controversial.
Scintigraphy at the time of an acute UTI provides information about
the extent of renal parenchymal involvement.
DMSA will identify most (>70 %) children with moderate to severe VUR
(Grade III or higher).
66. some experts suggest that DMSA be used as the initial imaging
test to identify children at higher risk for renal scarring
However, using DMSA as the initial test to identify high-risk
children is more expensive and involves greater exposure to
radiation. Furthermore, it may lead to identification of a large
number of children who may or may not be at risk for future
UTI.
It is unclear how to best manage children with positive acute-
phase DMSA scan.
Careful clinical follow-up of all children with UTI may obviate
the need for routine DMSA.
67. AAP and NICE guidelines suggest not using DMSA in the
routine evaluation of children with first UTI
Some experts recommend DMSA 6 - 12 months after acute
infection to detect the formation of scarring which would
require follow-up.
The NICE guidelines recommend DMSA 4-6month s after
acute infection for children < 3 years with atypical or
recurrent UTI and for children > 3 years with recurrent UTI.
68.
69. FOLLOW-UP
Recurrent UTI is a risk factor for renal scarring.
Infants and young children with a hx of febrile UTI or with
bowel and bladder dysfunction
should seek prompt evaluation for subsequent febrile illnesses
The evaluation of these episodes should include urinalysis and urine
culture.
Among children < 6 years, the risk of recurrence appears to be
increased in those
who are white, age 3 -5 years, and those with Grade IV - V VUR
70. Prompt diagnosis and effective treatment of recurrent febrile
UTI and treatment of bowel and bladder dysfunction may be
more important than identifying anatomic or functional
genitourinary abnormalities after the first febrile UTI in
preventing renal scarring.
The risk of renal scarring increases with recurrent episodes of
pyelonephritis:
5 % after the 1st episode to 10 % after the 2nd, 20 % after the
3rd, 40 % after the 4th, and 60% after the 5th
Primary care follow-up for infants and young children who have
had a febrile UTI should include
regular monitoring of height, weight, and blood pressure
71. Monitor for recurrent symptoms
Identify and treat bowel and bladder dysfunction
Prevention of recurrent UTI in children without VUR
• Antimicrobial prophylaxis
• Unproven interventions
• Surveillance cultures
• Cranberry juice
• Probiotics
72. Dilating
vesicoureteral reflux
(Grades III to V)
obstructive uropathy Renal abnormalities
Impaired kidney
function
Elevated blood
pressure
Bowel and bladder
dysfunction
refractory to primary
care measures
Indications for referral to a pediatric nephrologist or urologist include
73.
74.
75. Urinary tract infection (UTI) in neonates is associated with
bacteremia and congenital anomalies of the kidney and urinary
tract (CAKUT).
Upper tract infections (ie, acute pyelonephritis) may result in
renal parenchymal scarring and chronic kidney disease.
Neonates with UTI should be evaluated for
associated systemic infection,
and anatomic or functional abnormalities of the kidneys and
urinary tract.
76. Febrile term infants:
• Among neonates and young infants who present with fever, reported rates of UTI vary from 7 -
15 %.
• UTI typically presents in the second or third week after birth in term infants.
• The incidence of UTI is low (<2 %) in the 1st few days of life even in neonates who are
bacteremic..
Preterm infants
• Data are limited
• risk increases with decreasing gestational age and birth weight.
• the reported prevalence was 8 %
• extremely low birth weight (ELBW) infants had a greater risk of 13 %
77. Term infants
• E. coli is the most common pathogen (80
% of UTI).
• Other gram-negative bacterial causes of
UTI include Klebsiella,
Proteus, Enterobacter, and Citrobacter.
• Gram-positive pathogens
include Staphylococcus coagulase-
negative species, Enterococcus, and S.
aureus.
Preterm infants:
• Coagulase-
negative Staphylococcus and Klebsiella are
more likely causes of UTI in hospitalized
preterm infants,
• E. coli is less commonly seen
• Candida species, (particularly in ELBW
infants).
78. Term infants:
• Most UTIs in neonates represent upper tract infection rather than simple cystitis.
• Hematogenous spread of had been considered to be responsible for UTI because of the
higher frequency of febrile UTI, which was presumed to be due to bacteremia.
• ascending infection?
• Several virulence factors in E. coli account for the propensity of this organism to cause
UTI. (the pili that facilitate bacterial attachment to the uroepithelium and to ascend into
the kidney).
Preterm infants
• Hematogenous infection likely plays a greater role in preterm infants with UTI, as there is
a higher concordance rate of sepsis than in term infants.
79. HOST FACTORS
Male infants :
• account for 75% of neonates and young infants with UTIs
Uncircumcised males
• Incidence is 10-fold greater in uncircumcised vs circumcised males.
• The higher incidence in uncircumcised males is related to an increased rate of bacterial
colonization and enhanced bacterial adherence.
Kidney and urinary tract abnormalities
Prematurity
• because of their relatively immunocompromised status and the use of invasive devices
80. Term infants
Abnormalities are seen on US in 35 to 50 % of neonates and
young infants with UTI.
Most common findings are pelviectasis and mild hydronephrosis.
Major renal or urologic abnormalities (ie, high
grade hydronephrosis/VUR ) are found in 5 - 10 % of infants.
Other kidney and urinary tract abnormalities associated with UTI
include:
▪ Urinary obstruction, Ectopic ureter, Renal parenchymal disorders (eg,
PCKD, renal dysplasia)
81. Preterm infants
The prevalence of renal or urologic abnormalities would be expected
to be lower
Among preterm infants with UTI in NICU, abnormalities were seen
on US in 35 -40 %.
Most common findings were pelviectasis and mild hydronephrosis.
Major findings were seen in 5 % of patients (high grade
hydronephrosis/VUR, renal dysplasia, unilateral agenesis, partial
duplication of the collecting system, and horseshoe kidney.)
82. Term infants
• signs and symptoms of UTI in neonates are nonspecific.
• The most common clinical findings are:
• Fever
• Poor feeding , FTT
• Jaundice: typically is conjugated
• Vomiting, Loose stools
• UTI may be the presenting manifestation that identifies a neonate with an underlying
congenital anomaly of the kidney and urinary tract (CAKUT)
Preterm infants:
• The clinical manifestations of UTI in preterm infants are similar to those of term infants, with
the addition of apnea and hypoxia.
83. Laboratory tests:
Initial laboratory testing for evaluation
of UTI in neonates includes:
CBC with
differential
Urinalysis Urine culture Blood culture
For febrile or
ill-appearing
neonates, the
evaluation
should also
include LP
84. A urinalysis (microscopic and a dipstick analysis) includes
testing for leukocyte esterase and nitrite.
Urinalysis should always be performed in conjunction with a
urine culture to confirm or exclude the diagnosis of UTI in
neonates.
The presence of pyuria can be used to support a diagnosis of UTI
when the colony count of a catheterized specimen falls between
10,000 and 50,000 CFU/mL.
Urine should be obtained by either catheterization or
suprapubic aspiration.
85. Urine culture
Diagnosis of UTI is based upon a
positive urine culture collected
by bladder catheterization or
suprapubic aspiration (SPA).
"Clean voided" bag urine samples
should not be used for culture
The number of CFU defining a
positive urine culture varies
based on the method of
collection
• growth of a single pathogen
with a colony count of
≥50,000 CFU/mL,
• or a colony count between
10,000 and
50,000 CFU/mL with
associated pyuria
Bladder catheterization
•growth of a urinary pathogen is significant.
•The growth of one colony is equivalent to
1000 CFU/mL.
Suprapubic aspiration
86. * because the signs and symptoms of neonatal UTI are
nonspecific, several other disorders may present with
similar findings.
* Other infectious conditions including sepsis and
meningitis
Cultures of urine and other body fluids (eg, blood,
cerebrospinal fluid) distinguish UTI from these other infectious
diseases.
* Inborn errors of metabolism
87. 1. Sepsis evaluation:
• should be obtained in all infants in whom UTI is suspected
• The risk of concurrent sepsis in neonates with UTI varies from 4 to 7 % in
term neonates. The risk is greater in preterm infants
• A positive blood culture does not alter initial management in most patients,
but it may alter the duration of therapy.
A blood culture
• should be performed in ill-appearing infants or those with a fever
• 1-3% of infants with UTI have bacterial meningitis.
Lumber Puncture
88. * Because of the high prevalence of urinary tract abnormalities,
radiographic evaluation should be done for all neonates with
UTI.
* The first step renal US to identify structural abnormalities.
* VCUG is used to evaluate VUR in neonates with
abnormal renal ultrasound,
non-E. coli pathogen,
or recurrent UTI.
89. A renal US should be obtained after treatment is
initiated and the infant's condition has stabilized.
If prenatal US was normal and the study results are
accessible, postnatal renal US may not be necessary.
A normal US does not exclude VUR or renal scarring
90. VCUG should be performed in neonates with abnormal US.
Expert opinion differs whether VCUG is necessary in neonates
with normal US
"wait and watch" for most neonates with first-time UTI and normal renal US
VCUGs are generally performed only in neonates with abnormal renal US,
non-E. coli pathogen, or recurrent UTI.
VCUG is done in all neonates with first-time febrile UTI.
If a "wait and watch" approach is used, patients should be
monitored for recurrence.
If the patient develops a subsequent UTI, evaluation with VCUG is
appropriate.
91. Renal cortical scintigraphy (DMSA) may be used to
identify renal scarring and acute changes due to
pyelonephritis.
It is not generally helpful in the acute setting but may
be obtained as part of follow-up evaluation
particularly if renal damage is suggested by US.
Although CT also can identify these findings, it is not
suggested for routine use because of the exposure to
radiation.
92. TREATMENT
Treatment with intravenous broad-spectrum antimicrobial agents should
be initiated as soon as cultures (urine, blood, and CSF) have been
obtained.
Choice of agent and dosing
Initially parenteral empiric antibiotic therapy, then organism-specific therapy
based on the isolated organism and its antibiotic susceptibility.
Empiric therapy
The choice and dosing of empiric antibiotic therapy is the same as for neonatal
sepsis.
The combination of parenteral ampicillin and gentamicin provides coverage
for the most common bacterial pathogens.
93. Dosing
Doses are dependent on the weight and
chronologic age of the infant
Weight >2 kg
• ≤7 days
• ampicillin: 50 mg/kg/dose Q 8 hours
gentamicin: 4 mg/kg/dose Q 24 hours.
• >7 days
• ampicillin is 50 mg/kg/dose Q 6 hours;
gentamicin: 4 mg/kg/dose Q 24 hours.
Weight ≤2 kg
• ≤7 days:
• ampicillin: 50 mg/kg/dose Q 12 hours
gentamicin is 5 mg/kg/dose Q 48 hours.
• >7 days
• ampicillin: 50 mg/kg/dose Q 8 hours ,
gentamicin dosing is 5 mg/kg/dose Q 36 hrs
94. The choice of empiric regimen also depends on the clinical setting:
For hospital-
acquired infections,
vancomycin is
substituted
for ampicillin
If meningitis is also suspected,
higher doses of
antibiotics must be
used.
In infants >7 days old, a
third generation is added,
pending culture results
95. Organism-specific therapy
• based upon the isolated pathogen, its antimicrobial susceptibility, and if there
are concurrent infections
Response to therapy
• sterilization of the urine should occur within 48 hours of treatment
• Optimally, it should be confirmed by repeating the urine culture at that time
Duration of therapy
• the duration of antibiotic therapy is 10 - 14 days for neonates with
uncomplicated bacterial UTI.
• Longer treatment is often needed for fungal infections.
• antibiotic prophylaxis with oral amoxicillin (15 -20 mg/kg/day) is started until
radiographic evaluation has been performed.
96.
97. febrile female child suspected to
have UTI
< 2 years
≥ 1 risk factor*
urine analysis
and culture
clinical FU in 24 hours
and reassess the risk of
UTI
dysuria or frequency
urine analysis
and culture
abdominal pain
back pain
or new onsent incontinenece
urine analysis and
culture
UTI
unlikely
Risk factors:
history of UTI,
T>39°C,
fever without
source
ill appearance,
suprapubic
tenderness
fever >24 hours,
nonblack race
Whom to treat?
• children with Fever
(especially >39°C or >48
hours),
• Ill appearing,
• has costovertebral angle
tenderness,
• with known immune
deficiency,
• with known urologic
abnormality
yes
yes
yes
No No
No
98. febrile male child suspected to have UTI
< 2 years
circumcised
≥ 2 risk factor or
suprapubic
tenderness?
urine
analysis
and culture
clinical FU in 24
hours and
reassess the risk
of UTI
uncircumcised
≥ 1 risk factor
urine
analysis and
culture
clinical FU
in 24 hours
and
reassess
the risk of
UTI
> 2 yesrs
circumcised
consider UA if
multiple
urinary
symptoms
uncircumcised
dysuria or
frequency?
abdominal pain, back pain,
or new onsent
incontinenece
urine
analysis and
culture
UTI
unlikely
urine analysis and
culture
• Whom to treat?
• children with Fever
(especially >39°C or >48
hours),
• Ill appearing,
• has costovertebral angle
tenderness,
• with known immune
deficiency,
• with known urologic
abnormality
yes
yes
yes
yes
yes
No
No
No
No
99. First time UTI: Recurrent UTI > 1 time
First generation cephalosporin
Amoxicillin/clavulanic acid
Second generation cephalosporin
Check the previous culture result
Cefixime
Second generation cephalosporin
Trimethoprim sulfamethoxazole
In a child with Beta lactam allergy: Trimethoprim sulfamethoxazole
100. • Age <3 months
• Clinical urosepsis (eg, toxic
appearance, hypotension, poor
capillary refill)
• Immunocompromised patient
• Vomiting or inability to tolerate oral
medication
• Lack of adequate outpatient follow-up
• Failure to respond to outpatient
therapy
admission
• Ampicillin + Gentamicin
• Gentamicin
• Ceftriaxone
• Cefotaxime
• For beta lactam allergy:
• Gentamicin or amikacin.
• If ill appearing use two agnets:
aminoglycoside + a
flouroquinolone
Parenteral antibiotics for
inpatients
101. Duration
• Febrile UTI: for 10 days
• lower UTI: for 3-5 days
when to repeat urine culture (after 48 hours of therapy)?
• If the patient fails to respond clinically
• If the uropathogen is not susceptible (intermediate or resistant) to the
antibiotic that is being used for treatment.
102. Imaging:
Renal US
After the acute phase.
Children < 2 years of age with a 1st febrile UTI
Children of any age with
recurrent febrile UTIs
who have a family history of renal or urologic disease,
Who have poor growth, or hypertension
ASAP during the acute phase
with unusually severe illness and who do not respond as expected to
appropriate therapy
103. Imaging:
VCUG:
Children of any age with ≥ 2 febrile UTIs
Children of any age with a 1st febrile UTI and:
Any anomalies on RBUS, Poor growth or hypertension
DMSA scan:
4-6month s after acute infection
for children < 3 years with atypical or recurrent UTI and for children > 3
years with recurrent UTI
104.
105. VCUG if abnormal US, recurrent UTI, other than Ecoli
Renal US once stabilized
Start empiric antibiotics: ampi/Genta
Complete septic Workup: CBC, blood cx, LP
Take urine cx, UA
Febrile NB Vancomycin and
gentamicin: For
hospital-acquired
infections
If meningitis is
suspected,
Use higher doses
of antibiotics
In infants >7 days
old, add 3rd
generation
cephalosporin
Editor's Notes
It varies by age, race/ethnicity, sex, and circumcision status
Awareness of the prevalence of UTI in various subgroups of children enables the clinician to grossly estimate the probability of infection in the patient. This information is important in the evaluation of a child with suspected UTI
The presence of pathogens on the periurethral mucosa, however, is not sufficient to cause UTI.
Bladder and bowel dysfunction is an important and often overlooked factor in the pathophysiology of UTI in children. Up to 40 % of toilet-trained children with their first UTI and 80 % of children with recurrent (> 3) UTI report symptoms of bladder and bowel dysfunction. Bladder and bowel dysfunction is also a risk factor for persistent VUR, renal scarring, and recurrent UTIs. In both studies, bowel and bladder dysfunction was associated with increased risk of recurrent UTIs
An abnormal elimination pattern
Bladder and/or bowel incontinence
Withholding maneuvers
— Renal scarring, the loss of renal parenchyma between the calyces and the renal capsule, is a potential complication of UTI
Long-term consequences of renal scarring may include hypertension, decreased renal function, proteinuria, and end-stage renal disease.
Parental reporting of foul-smelling urine or gastrointestinal symptoms (vomiting, diarrhea, and poor feeding) is generally not helpful in diagnosing
urinary symptoms (dysuria, urgency, frequency, incontinence, macroscopic hematuria),
(approx 5 % with duration of 1- 2 days, 7.5 to 8 % with duration of 2-3 days, and 14 % with duration of >3 days). For every hour that antimicrobial therapy is delayed, the odds of new renal scarring increased by approximately 1 %; thus, a delay of 48 hours increased the risk of scarring by approximately 50 % (ie, from 5 to 7.5 %).
temperature ≥39°C (102.2°F) is associated with renal scarring ; elevated blood pressure may be an indication of chronic or recurrent UTI
(neurogenic bladder and recurrent UTI)
A delay of even a few hours increases both the false-positive and false-negative rates substantially
However, others suggest that bag urine samples can be used as a first step to determine whether a catheterized urine sample should be obtained for culture in young children. This approach is discussed separately.
However, a positive leukocyte esterase test does not always signal a true UTI because white blood cells (WBCs) may be present in the urine in other conditions (eg, Kawasaki disease).
because urine needs to remain in the bladder for at least four hours to accumulate a detectable amount of nitrite.
In young children in whom the prompt diagnosis and treatment of UTI are paramount, the enhanced urinalysis offers the best combination of sensitivity and specificity. However, enhanced urinalysis is not available in many outpatient settings
Enhanced urinalysis: An uncentrifuged specimen , hemocytometer (results reported as WBC/mm3), A Gram-stained smear
A delay of even a few hours increases both the false-positive and false-negative rates substantially
a higher colony count for the second uropathogen or growth of multiple organisms is considered contamination.
False-negative: failure to meet the definitions of significant bacteriuria
Obstruction of the ureter that interferes with the discharge of bacteria into the bladder
A delay in the treatment of febrile UTIs is associated with increased risk for renal scarring
; a delay of 48 hours or more increases the odds of new renal scarring by approximately 47 percent [10].
Other bacterial pathogens include
gram-negative : Klebsiella, Proteus, Enterobacter, and Citrobacter.
Gram-positive: Staph saprophyticus, Enterococcus, and, rarely, S. aureus.
as parenteral therapy followed by oral therapy. However, amoxicillin-clavulanate is associated with increasing rates of resistance.
Amoxicillin and ampicillin are not routinely recommended for empiric therapy because of the high rate of resistance of E. coli. Similarly, amoxicillin-clavulanate, first-generation cephalosporins (eg, cephalexin), and TMP-SMX should be used with caution, especially when pyelonephritis is suspected, because of the increasing rates of resistance to these drugs in some communities.
However, widespread use of fluoroquinolones is leading to increased resistance among other bacteria, and ciprofloxacin should not be routinely used as a first-line agent.
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases recommends that the use of ciprofloxacin for UTI in children be limited to UTI caused by Pseudomonas aeruginosa or other multidrug-resistant, gram-negative bacteria.
because parenchymal and serum concentrations may be insufficient to treat pyelonephritis or urosepsis
Inpatient parenteral therapy is indicated for children with
Age <2 months
Clinical urosepsis (eg, toxic appearance, hypotension, poor capillary refill)
Immune compromise
Vomiting or inability to tolerate oral medication
Lack of adequate outpatient follow-up
Failure to respond to outpatient therapy
caretakers will be able to adhere to the outpatient regimen
). In a retrospective cohort study, children hospitalized with UTI who had bacteremia more often received long-course (≥4 days) than short-course (<3 days) intravenous antibiotic treatment
However, little evidence is available to guide duration of antimicrobial therapy in children with febrile UTIs.
if the culture and sensitivity results are not yet available.
National Institute for Health and Care Excellence
Renal parenchymal inflammation during UTI may lead to renal scarring, although the predisposing factors are not well understood [64]. The role of renal parenchymal inflammation in the development of renal scars, and the potential role of anti-inflammatory agents in preventing renal scars has been evaluated in several studies
The ultimate value of detecting anatomic or functional abnormalities of the urinary tract depends upon the effectiveness of the interventions designed to prevent recurrent UTI and renal scarring
The false positive rate is between 2 -3%
If prenatal ultrasonography was performed and the results are normal we may elect not to perform RBUS (in children of any age
They define atypical UTI as serious illness, poor urine flow, abdominal or bladder mass; elevated creatinine, septicemia, infection with an organism other than E. coli, and failure to respond to antibiotics within 48 hours;
they define recurrence as ≥2 episodes of upper UTI, one episode of upper UTI plus ≥1 episode of lower UTI, or ≥3 episodes of lower UTI.
(to reduce the risk of false positive results secondary to renal inflammation during the acute episode) [3,61]. The decision to treat with prophylactic antibiotics pending results of imaging is discussed above.
VUR is the retrograde passage of urine from the bladder into the upper urinary tract. It
Decisions about performing a VCUG in infants and children with UTI must take into consideration the likelihood of VUR, severity of UTI, the importance placed on preventing recurrences, the cost and discomfort of the VCUG, and perceived likelihood of adherence to prophylaxis (if indicated).
Watchful waiting particularly if the family would prefer to avoid prophylactic antibiotics. These children are less likely to have VUR and VCUG results likely to affect management.
Early trials comparing antireflux surgery with antimicrobial prophylaxis in children with VUR showed no differences in rates of recurrent UTI or renal scarring, but the lack of a placebo or observation group precluded determination that either treatment was more effective than no treatment.
The RIVUR trial
Demonstrated unequivocally that prophylactic antibiotics decrease the risk of febrile, recurrent UTI.
However, antibiotic prophylaxis did not reduce the risk of scarring and was associated with antimicrobial resistance.
Randomized Intervention for Vesicoureteral Reflux (RIVUR)
addressed many of these issues. It evaluated the efficacy of TMP-SMX prophylaxis in preventing febrile or symptomatic UTI recurrences (primary outcome) in 607 children (two months to six years) who were diagnosed with Grade I to IV VUR after a first or second febrile or symptomatic UTI and were followed for two years [51].
Nearly twice as many children receiving placebo than children receiving prophylaxis were categorized as treatment failures (defined by two febrile UTIs, one febrile UTI and three symptomatic UTIs, four symptomatic UTIs, or new or worsening renal scarring).
dimercaptosuccinic acid
DMSA is injected intravenously, and uptake by the kidney is measured two to four hours later. Areas of decreased uptake represent pyelonephritis or scarring.
since most young febrile children with UTI have pyelonephritis and a positive DMSA,
In a systematic review of 33 studies, approximately 60 percent of children with initial UTI had DMSA scans consistent with acute pyelonephritis in the acute phase of illness, but only 15 percent had renal scarring at follow-up [70].
They define atypical UTI as serious illness, poor urine flow, abdominal or bladder mass, elevated creatinine, septicemia, infection with an organism other than E. coli, and failure to respond to antibiotics within 48 hours; they define recurrence as ≥2 episodes of upper UTI, one episode of upper UTI plus ≥1 episode of lower UTI, or ≥3 episodes of lower UTI.
comparing probiotics with placebo, probiotics did not prevent recurrent UTI [36]. The most commonly reported adverse effects included diarrhea, nausea, vomiting, constipation, and vaginal symptoms
Although cranberry juice in moderation is unlikely to be harmful, excessive intake may contribute to dental caries, diarrhea, and obesity.
As a result, urine cultures are not obtained for term infants who are being evaluated for early-onset sepsis during the first six days of life
rather than hematogenous spread from a remote source because of the microbiology of these infections (eg, E. coli) and the high incidence of urinary tract abnormalities.
Hematogenous infection likely plays a greater role in preterm infants with UTI, as there is a higher concordance rate of sepsis than in term infants.
This preponderance reflects the higher incidence of urinary tract anomalies in males and the increased risk of UTI in uncircumcised males.
The increased incidence in uncircumcised males persists during the first year after birth
Urinary tract abnormalities may contribute to UTI by several mechanisms, including inadequate urine flow, incomplete emptying of the bladder, and incompetent anatomic junctions that permit reflux of contaminated urine. Differences between males and females in voiding pressures and residual urine volumes explain in part why boys tend to get more UTIs in the first months of life (initially lower voiding pressures). With maturation, girls have more UTIs after the first months of life
The prevalence of renal or urologic abnormalities would be expected to be lower in preterm infants with UTI because many UTIs in this population are hospital-acquired.
Infants can have lethargy, irritability, tachypnea, or cyanosis, and may appear acutely ill.
abdominal distension resulting from ileus or enlarged kidneys caused by hydronephrosis.
Although a positive urinalysis is predictive of UTI in neonates, the test is not sufficiently sensitive or specific to be used alone to make the diagnosis. In addition, results of the urine culture are important for tailoring appropriate antibiotic therapy.
Urine specimens should be transported on ice and must be processed expeditiously to avoid further growth of organisms in the urine specimen. If the specimen cannot be processed quickly, it should be refrigerated.
SPA of the bladder urine is the most reliable technique to identify bacteriuria
.
As noted above, approximately 30 to 50 % of neonates with UTI have abnormalities on renal ultrasound, most commonly pelviectasis or mild hydronephrosis.
The prevalence of clinically significant VUR appears to be very low among infants with normal renal ultrasound and E. coli infection.
(eg, if the infant has a febrile illness, a urine sample should be obtained to evaluate for UTI).
The effectiveness of antimicrobial therapy for pediatric UTIs is demonstrated by the change in mortality between the pre- and post-antibiotic eras. The mortality of UTI was as high as 20 percent in the pre-antibiotic era. In contrast, when UTIs are appropriately treated with antibiotics, acute complications (eg, renal abscess, death) are uncommon.
This is because the causative agents are similar in neonatal sepsis and UTI, it is difficult to differentiate between the two based on presentation, and there is risk of concurrent infection
However, with increasing reports of resistant organisms, local surveillance of pathogens and antibiotic susceptibility patterns may be important to determine appropriate initial antibiotic therapy
For hospital-acquired infections, vancomycin is substituted for ampicillin since the predominant organisms include coagulase-negative staphylococci, Staphylococcus aureus, and Enterococcus species.
. If bacteriuria persists despite appropriate therapy, the urinary tract and other sites should be investigated to determine a potential reservoir of infection.
usually as a course of intravenous antibiotics