INFECTION AND INFLAMMATION OF

PAEDIATRIC GENITOURINARY TRACT

CHAIRPERSON – DR SHIVALINGAIAH M

CO-CHAIRPERSON – DR VISHWANATH

PRESENTER -- DR SHIVCHARAN
 Introduction
Definition:

• UTI is an inflammatory response of the urothelium to bacterial invasion that is usually

associated with bacteuria and pyuria.

• Urine is normally sterile, so UTI is presence of bacteria in a urine specimen.

• Bacteria is the most common cause of childhood urinary tract inflammation.

• Fecal-perineal-urethral route and subsequent retrograde ascent of bacteria that cause UTI.

• Potential for renal parenchymal and functional loss has prompted recommendations for
rapid diagnosis and evaluation of UTI.
Classification
A. On the basis of underlying defect
simple
complicated
B. Based on symptoms
Symptomatic UTI
Asymptomatic UTI
C. On the basis of region
involved
Upper UTI
Pyelonephritis
Lower UTI
Cystitis
Urethritis
Classification of UTI
Recurrent UTI may be subclassified into three groups :
• Unresolved bacteriuria : subtherapeutic level of antimicrobial, non-compliance with
treatment, malabsorption, resistant pathogens.

• Bacterial persistence : may be due to a nidus for persistent infection in the urinary
tract. Surgical correction or medical treatment for urinary dysfunction may be needed.
Protected sites include anatomic abnormalities, urinary calculi, necrotic papillae, or
foreign objects (i.e., urinary catheters, ureteral stents)

• Reinfection : each episode is a new infection acquired from periurethral, perineal or

rectal flora.
 Classification of UTI
• Severe UTI

Severe UTI is related to the presence of fever of > 39°C, persistent vomiting, and
moderate or severe dehydration.

• Simple UTI

A child with a simple UTI may have only mild pyrexia, but is able to take fluids and oral
medication. The child is only slightly or not dehydrated and has a good expected level
of compliance. When a low level of compliance is expected, such a child should be
managed as one with a severe UTI.
 Epidemiology
• During the 1st yr of life,
-M : F ratio is 2.8–5.4 : 1.
• Beyond 1–2 yr,
-M : F ratio of 1 : 10.
• Newborn : M=F .

• Only in first year of life males get more UTIs than females .

• Risk of UTI in uncircumcised boys is about ten times of circumcised boys (2.7% of boys vs 0.7% of girls). *

• The risk of having a UTI before the age of 14 yrs.

-1- 3% in boys
- 3-10% in girls
**Overall 1% boys & 3 % girls have UTI in 1st decade
* Wiswell and Hachey, 1993
Etiology - Microorganisms
A. Bacteria:-
• Gram negative bacteria
- Escherichia coli (80 % - 90 %)
- Klebsiella
- Proteus
• Gram positive bacteria
- Enterobacter
- Citrobacter
- Staph saprophyticus
- Group B streptococcus
- H. Influenza
- Staph. Aureus
 Etiology - Less common

B. Virus:-
-BK virus
-Ebstein Barr
-Adenovirus-11 (Acute hemorrhagic cystitis)
-Enteroviruses
-Coxsackie viruses
-Echoviruses

C) Fungus – recently received antibiotics or had indwelling urethral catheters.

-Candida spp. (most common) , Aspergillus spp.
-Cryptococcus neoformans
 Virulence factors
• Two types of bacteria- commensal and virulent bacteria.

• The term virulence comes from the Latin word for poisonous, veneficus, and is defined as the ability of an
organism to cause disease in a host.

• Recognized virulence factors include but are not limited to

(1) adherence to uroepithelial cells,

(2) bacterial nourishment in adverse conditions ,
(3) ability to hizack host defense,
(4) ability to damage host cells and other bacteria,
 BACTERIAL FACTORS
1. Bacterial adherence -
• Type 1 fimbriae -

-Most common mannose-sensitive adhesin is the type 1 fimbriae .

-Receptors for type 1 fimbriae are found in the muscular layers of bladder.

• P-fimbriae – Mannose-resistant adhesins

-Binding site for this adhesin appears to be α-galactose-(1-4), found on epithelial cells and red blood cells.

-70% of strains causing clinical symptoms of pyelonephritis .

-Proteins located at the tip (G-tip proteins ) determine the fimbria’s specific attachment properties.

-Three classes identified, of which only class II and class III P-fimbriae have uropathogenic potential.
2. Aerobactin
• All
.
living cells, including bacteria, need iron.

• E. coli uses iron for oxygen storage and transport, DNA synthesis, electron transport, and metabolism of
peroxides

• The siderophore aerobactin extracts iron from host iron-binding proteins and delivers the iron to bacterial
iron centers

3.Hemolysin
• The cytolytic protein secreted by most hemolytic E. coli is known as alpha hemolysin .

• Alpha hemolysin lyses erythrocytes of all mammals and is toxic to a wide range of host cells
contributing to inflammation, tissue injury, and impaired host defenses .

• In human UTIs, hemolysin production is most common in bacterial strains from patients suffering
pyelonephritis.
4. Capsular Polysaccharide
.

• E. coli has more than 80 types.

• Are linear polymers that coat the bacterial cell, interfering with antigen detection and
protecting the cell from host defense detection.

• The capsules of most uropathic E. coli are composed of group II polysaccharides

• Also called as K antigens.

• Encapsulated K bacterial strains are less well phagocytosed and also have
anticomplementary activities.
 Other virulence factors

• 1) Endotoxin: A lipopolysaccharide present in the bacterium’s cell wall, endotoxin, is

responsible for initiating the acute inflammatory response common to Gram-negative
infections.

• 3) Colicin: Colicin kills other bacteria in the vicinity of the E. coli producing it. The colicin V
plasmid is also thought to encode for an iron uptake system that further promotes the
survival and pathogenicity of colicin-producing organisms
Role of bacterial virulence in renal scarring
• Lomberg et al concluded that reduced host resistance essential for renal scarring after APN.

• More virulent bacteria may elicit a more rigorous inflammatory response than less virulent clones and are
thus cleared more rapidly.

• Children infected with more virulent bacteria present earlier with symptoms such as fever, resulting in
more prompt diagnosis and treatment.

• Coincident with an inflammatory response, P- and type-1 fimbriated E. coli were demonstrated to be
more rapidly cleared than non-fimbriated strains.
 Host factors
Gender and Age
• About 2.7% of boys, compared to 0.7% of girls, experience a UTI during the first year of life .

• After 1 year of life, the incidence of UTI development drops to 0.03% to 0.2% in males and
increases to 1% to 3% in females .

RACE
• More commonly in Caucasian girls compared to girls of other races.

• UTIs most prevalent in Caucasian children, followed by Hispanic, and then African-
American girls .
• In boys UTIs more common in Hispanics, followed by Caucasians, and least common in
African-American boys.
Fecal and Perineal Bacterial Colonization
.

• Bacteria that colonize the gut, perineum, and periurethral area ascend via a retrograde fashion.

• During first few months after birth, the periurethral area of boys and girls are heavily colonised by aerobic
bacteria, which decreases after 6 months and is unusual after 5 yrs.

• Infants born to bacilluric mothers have a fourfold greater risk of urinary tract infections.

• Normal periurethral flora may even be protective against urinary infection by competitive interference
with attachment of uropathogenic bacteria.

• This can be altered by the administration of antimicrobial agents, given for any reason.
 .

Prepuce

• Increased risk for UTI in uncircumcised boys compared with both girls and circumcised boys.

• Over 90% of boys with febrile UTIs during the first year of life are uncircumcised.

• Uropathogenic P-fimbriated E. coli adhere well to the mucosal surface of the prepuce, whereas non-
pathogenic E. coli do not.

• Circumcision in boys who have risk factors for UTI such as antenatally detected hydronephrosis associated
with posterior urethral valves, megaureters, high-grade VUR, is Justified.

• Multiple studies demonstrate that circumcision reduces the rate of UTI development in the first 6 months of
life by almost tenfold.
Dysfunctional elimination syndrome
.

• Koff originally coined the term dysfunctional elimination syndrome, which defined children without any
neurologic disorder but who suffered from infrequent voiding, constipation, and/or bladder overactivity .

• Dysfunctional elimination present in 36% of the girls and 20% of the boys with VUR.
• Frequency of constipation associated with pediatric bladder dysfunction ranges from 30% to 88%

• Common voiding disorders in children prone to UTI -

(A) small-capacity, unstable bladder characterized by frequency, urgency, posturing, and wetting

(B) infrequent voider (‘lazy bladder syndrome’) characterized by very infrequent voiding, a large-
capacity bladder, paradoxical incontinence (wet despite a large bladder capacity), and constipation
Bladder dysfunction two types :
(1) overactive bladder-urinary urgency with or without urge incontinence, usually with frequency and nocturia.
.

(2)dysfunctional voiding-no neurologic issues who exhibit increased activity of their pelvic floor during voiding.

• Treatment of a child's bladder and bowel issues reduces recurrent UTIs and improves VUR resolution.
• Conservative therapeutic measures for treating the child with bladder dysfunction include voiding behavior
modification with timed voiding schedules and treatment of constipation.
• Targeted interventions may include pharmacologic therapy, biofeedback, electrical stimulation therapy,
surgery, clean intermittent catheterization, or a combination of these therapies

• Bladder overactivity treated with anticholinergics alone resulted in VUR resolution or improvement in 44% to
79% of children.
• Dysfunctional voiding treated with biofeedback resulted in VUR resolution in 55% to 63% of cases and
improvement in VUR grade after 1 year of therapy .

• It took 1.5 years longer for primary VUR to resolve in children with dysfunctional elimination.
Neurogenic Bladder
.

• Due to elevated bladder storage pressures risk of hydronephrosis and renal damage increases.

• When left untreated, bladders that fill or empty at abnormally high pressures, unable to clear the bacteria
spontaneously.

• CIC facilitate the emptying of the bladders of patients with neurogenic bladder and lower chronic bladder
distention and bladder pressure.

• The use of sterile versus nonsterile, single versus multiuse, and lubricated versus nonlubricated catheters have
shown no benefit in reducing the risk of UTI development*

• Risk factors for UTI development in men and women treated with intermittent catheterization included high
mean catheterization volume in women and low frequency of catheterization in men.

*Moore et al, 2007

Heredity .

• The daughters of mothers who had been bacteriuric in childhood show a higher incidence of UTI, and female
siblings tend also to show a higher incidence of bacteriuria.

• There is role of ABH, Lewis antigens (Lea, Leb, Lex, and Leh), P, Kell, Duffy systems in host susceptibility to
urinary infection.

• Blood group antigens can be found on the surfaces of many epithelial cells in the body, including vaginal and
uroepithelial cells, and as secreted antigens in mucus in addition to on erythrocytes.

• Bacterial colonization of epithelial surfaces is facilitated by cell-surface-bound antigens, whereas secreted

antigens mitigate against colonization by virtue of competitive inhibition.

• Adult women with Le (a−b−) and Le (a+b+) blood phenotypes are three times as likely to have recurrent UTIs
compared to women with the Le (a−b+) phenotype.
Immunologic factors
.

• Increased susceptibility of UTI in first few months may in part be a result of an immature immune system.
• Serum IgG is lowest from age 1 to 3 months .
• The urine of newborns has nearly undetectable levels of IgA that increase during the first year of life,
particularly in breastfed as compared with non-breastfed infants.
• Additionally, breast milk contains T and B lymphocytes, cytokines, growth factors and, most importantly,
antibodies that may act synergistically to decrease the breastfed infant’s risk of UTI.

Iatrogenic Factors

• Catheter-associated UTI is the most common nosocomial infection.

• The risk of UTI increases with the duration that the catheter is in place.
• overall incidence of bacteriuria is 8% and ranges from 3% to 10% per day .
• Should be judicious use of urinary catheters and the removal of urethral catheters in hospitalized patients as
soon as they are no longer medically necessary.
Urinary inhibitors
.

• pH
• Extremes of urine osmolarity
• Free Tamm–Horsfall protein

Vaccination

Options
• Vaginal suppository containing 10 heat-killed strains of uropathogenic bacteria, known as Solco-Urovac
• Type 1 pilus–associated adhesin FimH
• UPEC-associated iron acquisition systems
• Use of purified bacterial iron receptor proteins for vaccination 
 IreA and LutA - protection against cystitis, whereas vaccination with another iron receptor,
 Hma - protection against pyelonephritis, but not cystitis
 Urinary Tract Abnormalities
• A reason for imaging to be part of the UTI evaluation in children comes from close
association of UTI and genitourinary malformations.

• Imaging evaluation of children with UTI reveal that 5% to 10% of children have obstructive
urinary tract lesions, and an additional 21% to 57% have vesicoureteral reflux

• Using imaging evaluation triggered by febrile UTI still reveal significant numbers of
genitourinary abnormalities.
• A more recent retrospective examination of imaging results obtained from children in
Taiwan after a first febrile UTI showed
• 56.1% to have vesicoureteral reflux.
• 29.5% grades III to V vesicoureteral reflux.
• 17% renal hypodysplasia.
• 2% hydronephrosis .
Surgically Correctable Causes of Bacterial
Persistence in Children
• Infection stones
• Infected non-functioning or poorly functioning
kidneys or renal segments
• Infected ureteral stumps after nephrectomy
• Vesicointestinal or urethrorectal fistula
• Vesicovaginal fistula
• Infected necrotic papillae in papillary necrosis
• Unilateral medullary sponge kidney
• Infected urachal cyst
• Infected urethral diverticulum or periurethral gland
 Anatomical abnormalities of the upper urinary tract
Vesicoureteral reflux

• VUR has been identified in 1% to 2% of all newborns.

• It is found in 25% to 40% of children after their first episode of UTI (vs 0.4–1.8% in children without UTI).

• The risk for both acute pyelonephritis and subsequent renal scarring is directly related to the severity of
VUR.

• In a compilation of 10 published clinical studies of children with febrile UTIs, DMSA renal scan abnormalities
have been reported in 50–80% of children.

• VUR often undergoes spontaneous resolution.

• The time from first UTI to resolution of VUR is 6-7 yrs.

• Management
. options include observation, continuous antibiotic prophylaxis, endoscopic injection, or
open operative correction.

• Decreased febrile UTIs as the only benefit of surgical management.

• Surgical treatment reserved –

High grade and unilateral reflux,

Recurrent UTIs despite antibiotic prophylaxis, and
Noncompliance with antibiotics
Persistence beyond 9 yrs of age .

• Endoscopic management involves subureteral or intraureteral injection of bulking agent with

dextranomer/hyaluronic acid.
PATHOGENESIS
 Natural history
Asymptomatic bacteriuria
• Asymptomatic bacteriuria (ASB) is defined as the presence of two consecutive urine specimens yielding
positive cultures (>105 CFU/mL) of the same uropathogen in a patient who is free of any infectious symptoms.

• ASB occurs in fewer than 1% of full-term infants and in 3% of premature infants.

• Most common organism obtained from these ASB individuals is E. coli.

• Antimicrobial therapy in these unlikely to prevent later asymptomatic or symptomatic bacteriuria.

• Low risk of developing long-term sequelae related to the bacteriuria.

• Routine antimicrobial therapy is not recommended.

• Screening children for ASB is not cost-effective.

Cystitis
• Is rarely associated with significant long-term morbidity.

• Typical symptoms in toilet-trained children include dysuria, frequency, urgency, and/or sec.-onset enuresis.

• Fever and systemic complaints are generally not a feature.

• These irritative LUTS can be seen in the absence of bacterial cystitis, mandating that a specimen for urine
culture be obtained prior to institution of therapy.

• Approximately 10% of susceptible girls will have a recurrent infection shortly after completion of a course of
antibiotic therapy.

• Treatment is determined by the recurrence rate of infection and the type of underlying voiding and bowel
disorder.
Bacterial Nephritis

• Inflammation from bacterial infection within the kidney begins to spread throughout the kidney in an
increasingly suppurative process with heavier leukocytic infiltrate and focal areas of tissue necrosis.

• Generalized form  acute bacterial nephritis.

• Localized form  acute focal bacterial nephritis or lobar nephronia .

• Computed tomography (CT) findings include global renal enlargement, inflammatory changes in the
perirenal fat, and thickening of Gerota fascia.

• On contrast images there may be ill-defined, nonhomogeneous-decreased parenchymal enhancement that

typically is wedge shaped.
 Pyelonephritis
• Acute pyelonephritis represents the most serious type of UTI in children.

• Has the potential for causing irreversible damage.

• Fever and flank pain or tenderness associated with pyuria and positive urine culture.

• In the majority of cases, laboratory evaluation reveals an elevated serum WBC count, ESR, and/or CRP.

• Clinical and laboratory parameters are associated with high false positive and/or false-negative rates.

• This is particularly true in neonates and young infants, an age group at greatest risk for renal scarring following
pyelonephritis.

• Kaack et al have shown that granulocyte aggregation within capillaries leads to vascular occlusion. Renal
ischemia is then evidenced by a transient rise in circulating renin levels.
 Diagnosis of urinary tract infection
• The classic signs and symptoms for UTI are usually lacking in the very young.

• Symptoms are typically nonspecific and include fever, irritability, poor feeding, jaundice, failure to
thrive, vomiting, diarrhea, abdominal distention, or foul-smelling urine .

• UTI requires a demonstration of the presence of the infecting organism in the urine .

• Infecting organism is routinely proven by urine culture In children who have no alternative fever
source from history or physical findings, UTI accounts for greater than 5% of fevers.*

*American Academy of Pediatrics

Presentations
Clinical features

a) < 2 month :
Nonspecific symptoms and signs – irritability, poor feeding, fever , Jaundice

b) 2month -1 year:
Fever/Hypothermia
Vomiting, Diarrhea
Sepsis
Irritability
Lethargy
Malodorous urine
 Presentations
c) 1-5 years:
Abdominal pain- Flank /back/ Supra pubic
Vomiting ,diarrhea
Constipation
Abnormal voiding - Urgency, urinary incontinence,dysuria
Malodorous Urine
Fever/febrile convulsion
Failure to thrive
 Presentations
d) >5years:
Dysuria
Frequency
Urgency
Abdominal discomfort
Fever
Malodorous urine
.

• .
 Adolescents
• Although E. coli is still the most common UTI in female adolescents, the second most common is
Staphylococcus saprophyticus.

• Adolescent females with dysuria and frequency should be evaluated for sexually transmitted infection (STI).

• The prevalence of Chlamydia is 13% to 26% and Neisseria gonorrhea is about 2% to 10% in this population.

• For this reason, considering STI in this group is more important for the differential diagnosis.

• Urethritis can be caused by Neisseria gonorrhoeae, Chlamydia trachomatis, or Ureaplasma urealyticum as

well as routine uropathogens.*

*U.S. Preventive Services Task Force, 2007

Localizing symptoms:
Symptoms of urethritis: Features of cystitis:
• Dysuria • Afebrile usually
• Reluctance to void • Frequency
• Perineal discomfort • Enuresis
• Dysuria
• Vaginal irritation and erythema in girls • Reluctance to void
• In older boys, urethral discharge
• In adolescent girls associated with PID

Features of pyelonephritis:
• Fever and systemic signs
• Older children
Flank pain or abdominal pain
• Younger children
Fever, irritability, vomiting, poor feeding
 Physical examinations
• Temperature • Fecal mass
• Pallor • Signs of vulvitis
• Anthropometry • Spine
• Tenderness-Lower abdomen • Lower limb reflexes
-Renal angle • Associated with UTI-Prune belly syndrome
• Renal mass • Anorectal anomalies
• Palpable bladder • Genital examination
• Peripheral reflexes in the lower extremities Boys- meatal stenosis
• lower back for sacral dimpling or circumcision status
cutaneous abnormalities (occult spinal Girls- vulvovaginitis
dysraphism).
labial adhesions
 LABORATORY EVALUATION

• Because of the nonspecific symptoms and signs, the diagnosis of a UTI requires the demonstration of an
infectious agent or agents in the urine.

• In addition, the AAP guidelines also require evidence of pyuria for the diagnosis of a UTI to help
distinguish a true infection from ASB or contamination .

• Dipstick
• Microscopy
• Culture & sensitivity
Methods of urine collection
.

Chance of collecting a contaminated urine specimen increases with the decreasing

degree of invasive collecting methods.

Different guidelines suggest different methods of collecting urine specimens

• Clean catch or midstream sample - NICE

• Supra pubic aspiration – AAP
• Urinary bag sample –small children
• Catheter specimen – AAP

The results of a bag urine specimen are reliable only when the specimen is negative.
• A urinalysis specimen should be performed on urine less than 1 hour after voiding if the
specimen has been maintained at room temperature or less than 4 hours if refrigerated.

Urine dipstick
88 % sensitive

• Leukocytes
• Protein
• Red blood cells
• Leukocyte esterase – For WBC , esterase in neutrophils
• Nitrite - high specificity 98 % , first morning sample most sensitive, positive nitrite test is very
likely to reflect a true UTI.
 Routine Microscopic Examination
• White Blood Cells - pyuria is defined as ≥5 WBC/PHF in centrifused or ≥10 WBC/mm3 in an uncentrifuged
sample
• Bacteria: - bacteriuria is the presence of any bacteria per hpf. - Gram stain.

• The most reliable rapid test for diagnosing a UTI consists of the microscopic identification of bacteria on both
unstained and Gram-stained uncentrifuged fresh urine specimens, more sensitive than pyuria.

• UTI in children is still best defined by a urinary leukocyte count of greater than or equal to 10/mm3 and
greater than or equal to 50,000 colony-forming units (CFU)/mL on culture.

• The combination of positive leukocyte esterase and nitrite testing, and microscopic confirmation of bacteria,
has almost 100% sensitivity for detection of UTI.

• When all are negative, the NPV approaches 100%.

Urine Culture
• The definition of what constitutes a true positive urine culture based on the number of CFU per mL of urine.

• Threshold used to diagnose a positive urine culture - greater than or equal to 105 CFU/mL of a uropathogen.

• AAP guidelines suggest a reduction from 105 CFU/mL can be used in children aged 2 to 24 months.

• These new guidelines recommend that 50,000 CFU/mL, now including the requirement of a positive urinalysis
for pyuria from a urine sample obtained by catheterization or SPA, be used for the diagnosis of UTI.*

*Downing et al, 2012

• European Association
. of Urology - 104 CFU/mL is indicative of UTI with a midstream specimen if associated
with symptoms, but 105 should be used if there are no symptoms .*

• RCH Melbourne Guidelines - any gram-negative bacteria by SPA and greater than 103 CFU/mL by
catheterization is consistent with UTI.

• ISPN guidelines - >104 CFU/mL for a catheterized specimen and more than 105 CFU/mL for a
midstream/clean-catch specimen.

Contamination is more if –
low colony counts
cultures with heavy, mixed growth of bacteria
cultures growing nonpathogenic organisms include Lactobacillus, coagulase-negative
staphylococci, Corynebacterium , alpha-hemolytic streptococci, and Candida

*Downing et al, 2012

 Serum Tests Indicating Urinary Tract Severity
• Complete blood counts , ESR , C-reactive protein (CRP), and interleukins 6 and 8 (IL-6, IL-8).

• CRP greater than 7 mg/dL has been associated with serious infection in febrile children age 1 to 36 months.

• Serum procalcitonin, a hormonally inactive precursor of calcitonin produced in the thyroid, is elevated in
sepsis and appears to be in the systemic circulation during severe inflammation.

• Elevation of serum procalcitonin is reported to correlate better than ESR or CRP with pyelonephritis and to
predict risk of renal scarring and may be particularly useful in infants.

• Sensitivity and specificity of a procalcitonin level greater than or equal to 0.5 ng/mL for detection of APN
71% and 72%, respectively, and 70% sensitivity and 50% specificity for late renal scarring.
 .

Test Sensitivity% (range) Specificity%

(range)

Leucocyte esterase 83 (67-94) 78 (64-92)

Nitrite 53 (15-82) 98 (90-100)

Leucocyte esterase and Nitrite positive 93(90-100) 72 (58-91)

Microscopy : WBC 73 (32-100) 81 (45-98)

Microscopy: bacteria 81 (16- 99) 83 (11- 100)

Leucocyte esterase , nitrite and microscopy positive 99.8 (99-100) 70 (60-92)

 Culture criteria for diagnosis of UTI
Method of collection Colony counts Probability of infection(%)

Suprapubic aspiration Gram –ve bacilli: any number >99

Gram +ve cocci: >few thousands
Catheterisation >105 95
104 to105 Infection likely
103 to 104 Suspicious: repeat
<103 Infection unlikely
Clean voided(male) >104 Infection likely
Clean voided (female) 3 specimen >105 95
2 specimen: 105 90
1 specimen: >105 80
5x104 to 105 Suspicious: repeat
104 to 5x104 Symptomatic suspicious
104 to 5x 104 Asymptomatic infection
<104 Infection unlikely
Indications for further investigations:

1. Girls younger than 3 years with a first UTI

2. Boys of any age with a first UTI
3. Children with recurrent UTI
4. First UTI in a child of any age with a family history of renal disease,
abnormal voiding pattern, poor growth, hypertension
 Dimercaptosuccinic acid (DMSA) renal scan
• Renal cortical scintigraphy with 99mTc DMSA has emerged as the imaging agent of choice for acute
pyelonephritis and renal scarring in children with a sensitivity of 87–89% and specificity of 100% .

• The maximum sensitivity of DMSA for detection of APN is within 1 week from the onset of symptoms.

• The NICE guidelines recommend DMSA 4 to 6 months after acute infection for children.

• Cortical renal scan with DMSA combined with single-photon emission computed tomography (SPECT) is
considered by many as the gold standard for identification of lesions in the renal parenchyma.*

• DMSA scan in APN shows focal areas of diminished uptake of DMSA with preservation of the renal contour.

• Patients with clinical findings consistent with acute pyelonephritis have abnormal DMSA scan in 50-80 % .

• The radiation dose for DMSA scintigraphy has been estimated as 1 mSv .

*Craig et al, 2000; De Palma and Manzoni, 2013

 .

The timing of the study –

 If one is attempting to document acute

pyelonephritic inflammatory changes, the
•. DMSA renal scan is best obtained early within
the first several days of the acute episode.

 If the primary goal is to document irreversible

renal scarring following an episode of infection,
then the study should be delayed for 6 months
following the acute infection. some suggest
waiting up to 1 to 2 years for resolution of any
reversible defects.
 Sonography
• It is noninvasive, is free from radiation exposure, and is widely available makes its routine
use widely accepted for children with a history of UTI.

• Abnormalities in about 15% of infants and young children after their first febrile UTI.*

• It is estimated that 1% to 2% of these children will exhibit an abnormality that requires

additional evaluation demonstrating the size, shape, and presence of both kidneys.

• Ultrasound helps screen for previously undiagnosed congenital abnormalities, urinary

tract obstruction, hydronephrosis, stones, pyonephrosis, and fluid collections such as
renal or perirenal abscesses.

Subcommittee on Urinary Tract Infection et al, 2011

.
 Radiographic Imaging : Controversies with Imaging Strategies
• NICE guidelines recommend

 Routinely obtaining an ultrasound in children less than 6 months old and in those more than 6 months to
children with either a recurrent UTI or an atypical UTI as defined by being seriously ill, by poor urine flow, by
abdominal or bladder mass, by raised creatinine, septicemia, by failure to respond to treatment within 48
hours, or by infection with a non–E. coli organism.*

• AAP guidelines recommend

 Obtaining a renal ultrasound in all children less than 2 years of age with a febrile UTI, but these guidelines
no longer recommend routinely performing a VCUG in these children if the ultrasound is normal.**

*NICE, 2013
**Subcommittee on Urinary Tract Infection et al, 2011
Voiding Cystourethrogram
• Gold-standard imaging technique for the detection and grading of VUR.

• Provides anatomic information about the bladder such as size and shape and the presence of trabeculations or
diverticula.

• The voiding images about the function of the urinary sphincters as well as any urethral obstruction.
• A negative VCUG does not completely eliminate the possibility of VUR.

• A cyclic VCUG, in which bladder is filled, child voids, and the bladder is filled a second time and is followed by
voiding, will increase the sensitivity for VUR detection as well as the detection of an ectopic ureter.

• Radiation reported from VCUG varies from 0.5 to 3.2 millisievert (mSv) with mean 1 mSv.

• Iodinated contrast medium  anatomic resolution and ability for grading is significantly higher.

• Nuclear imaging agents such as technetium-99m pertechnetate  sensitivity for the detection of VUR is higher
• Both direct and. indirect cystography techniques are used.

• Direct radionuclide cystography allows continuous monitoring for reflux throughout the study without
additional radiation exposure.

• It is reported to be more sensitive than contrast cystography for the diagnosis of reflux. Whereas precise
grading of VUR is limited, it can usually be categorized as mild, moderate, or severe.

• The radiation dose from radionuclide cystography reportedly is 50–200 times less than standard techniques
using contrast cystography, making it ideal for the follow up for VUR and for results of antireflux surgery .

• Indirect radionuclide cystography uses 99mTc DTPA which is excreted by glomerular filtration.

• The presence of reflux can be assumed when radioisotope counts increase in the renal areas after voiding.

• Indirect cystography is less reliable for the detection of VUR

.
.
.

• .
Computed Tomography
• CT provides detailed anatomic imaging and excellent sensitivity for determination of kidney involvement
with infection.

• High degree of radiation and potential problems with contrast media, severely limit any benefit of this
imaging modality in a child with a UTI.

• The mean radiation dose for a pediatric abdominal/pelvic CT is 10 to 15 mSv.*

• Useful for distinguishing inflammatory changes from the tumor at times when the acute ultrasound is
suspicious for a renal mass.

• Typical findings associated with renal infection and inflammation include cortical regions of
hypoattenuation, wedge-shaped defects, a loss of the corticomedullary differentiation, and striations.

(Miglioretti et al, 2013)

Seriously ill, poor urine flow, abdominal or bladder mass, raised creatinine, septicemia, failure to respond to correct antibiotic treatment
within 48 hr, or infection with non–Escherichia coli organisms.
†Dilation on ultrasonography, poor urine flow, non–E. coli infection, or family history of VUR.
‡Abnormal prenatal ultrasonography of the urinary tract, family history of VUR, septicemia, renal failure, age <6 mo in a male
infant, likely noncompliance of the family, abnormal bladder emptying, no clinical response to correct antibiotic treatment within 72 hr, or
non–E. coli infection.
 Algorithm for evaluation of children with UTI

• .
 Renal scarring
• A higher prevalence of renal scarring has
been reported in children with secondary
VUR associated with functional or
anatomic bladder outlet obstruction

• In the face of VUR and normal voiding

pressures, renal scarring occurs only when
urinary infection is present.

• Portions of the kidney at risk for scarring

are those susceptible to pyelotubular
backflow (intrarenal reflux), based on
papillary morphology and configuration.
• Infection, not reflux alone, is a prerequisite
for acquired renal scarring
•.
.
 .

• Renal scars detected by DMSA scintigraphy appear as

focal or generalized areas of diminished uptake of
radioisotope associated with loss or contraction of
functioning renal cortex.

• This may appear as thinning or flattening of the cortex

in some kidneys, while in others renal scars appear as
classic discrete wedge shaped parenchymal defects.

• In contrast, defects associated with acute pyelonephritis

are more typically characterized by focal areas of
diminished uptake but with preservation of the normal
renal contour.
 Sequelae of renal scarring
Hypertension

• Approximately 6–13% of children with scarring will develop HTN.

• The risk of hypertension increased with age and length of follow-up

• Hypertension was significantly more common in those with severe bilateral parenchymal scarring

• The development of hypertension is clearly related with a history of recurrent episodes of pyelonephritis
associated with moderate or severe VUR

• The etiology of hypertension associated with renal scarring is controversial with likely involvement of
renin–angiotensin– aldosterone (RAS) system
• Renal insufficiency
.

• The actual risk of renal insufficiency secondary to postpyelonephritic renal scarring is unknown.

• ESRD associated with ‘reflux nephropathy’ represented 7% of all new cases of ESRD.

• Incidence of renal insufficiency in patients with postpyelonephritic renal scarring increases with age.

• Most patients (90–100%) with reflux nephropathy and ESRD have focal segmental glomerulosclerosis,
almost always associated with proteinuria.
Treatment goals
Treatment has four main goals:

• Elimination of symptoms and eradication of bacteriuria in the acute episode.

• Prevention of renal scarring.
• Prevention of a recurrent UTI.
• Correction of associated urological lesions.
MANAGEMENT OF UTI
 Management
• Whether child requires hospitalization or outpatient parenteral or oral treatment
depends upon the age, clinical status, compliance for prescribed treatment.
• Infants more likely to develop electrolyte abnormalities including hyponatremia and
hyperkalemia so require hospitalization and parenteral antibiotics.*

Indications for hospitalization-

 Infants younger than 2 month of age.

Toxic presentation or dehydration.
Intolerance to oral intake.
Questionable compliance with antibiotics.**

• Neonates require initial hospitalization and full septic evaluation along with parental
antibiotics.
*Brady et al, 2010
** Royal Children's Hospital Melbourne,2011
 Children and Outpatient Therapy

• In appropriate infants and young children with presumptive febrile UTI-

- Taking fluids
- Cooperative and reliable parents
- With whom daily contact is possible

• National and local antimicrobial resistance to common organisms that commonly infect
the urinary tract must be considered in the selection of both the agent for initial treatment
and that for prophylaxis.

• Generally, parenteral treatment continues for 2 to 4 days until fever is gone, the child is
able to take adequate fluids, and bacterial sensitivities are available to allow treatment
with an oral drug with a narrow spectrum.
 Duration of treatment
• In children, antibiotic treatment lasting 7 to 14 days is recommended for febrile UTI because
shorter courses have been proven inferior.*
• With severe infections, such as acute lobar nephronia, a longer course of antibiotics of at
least 3 weeks is sufficient in most cases.
• Analysis has shown that no follow-up urinary culture after 48 hours is required, if organisms
are sensitive to the antibiotic selected.

*Michael et al, 2003

 Antimicrobial Agent Selection
• E. coli remains the most common pediatric uropathogen (>80% of UTIs)

• While awaiting culture results , TMP-SMX and amoxicillin are used in approx. 50% of outpatient UTI visits but
these might be poor empiric choices because of high resistance rates of E. coli.

• Nitrofurantoin or a first-gen. cephalosporin is an appropriate narrow-spectrum antibiotic choice.

• Empiric treatment of acute UTI should be based on regional antibiograms that are revised and published on an
annual basis, as uropathogen prevalence and resistance patterns will vary regionally and change with time.

Predictors of resistant uropathogens –

• Diabetes
• recent hospitalization,
• recent use of antibiotics
• presence of urinary malformations, urethral catheters, and antimicrobial prophylaxis
Nitrofurantoin
• Nitrofurantoin is an effective urinary prophylactic agent because its serum levels are low, urinary levels
high, and it produces minimal effect upon the fecal flora .
• caused acute allergic pneumonitis, neuropathy, and liver damage.
• Long-term treatment has been associated with rare cases of pulmonary fibrosis.
• Children with glucose-6-phosphate dehydrogenase deficiencies should not take nitrofurantoin, because it
is an oxidizing agent that can cause hemolysis.

Sulfonamides
• Sulfonamides act by competitively blocking the conversion of para-aminobenzoic acid to folic acid
• Sulfonamides are most effective against E. coli but also may be effective against other Gram-negative and
Gram-positive organisms.
• Sulfonamides are well tolerated by children, are inexpensive, produce few side effects and are effective
agents for short-term acute therapy of uncomplicated infections
• interfere with bilirubin excretion so cause jaundice and minor reactions.
TMP–SMX
• The TMP–SMX combination is useful both in the management of simple cystitis and for
.

long-term antibacterial prophylaxis. This combination has a diminished effect on bowel

flora.
• Trimethoprim interferes with dihydrofolic acid reductase, and sulfa methoxazole blocks the
conversion of para-aminobenzoic acid to dihydrofolic acid.
• Neutropenia and thrombocytopenia are not uncommon with its use.
Ampicillin
• Ampicillin is the most widely used penicillin in the treatment of UTIs. not well absorbed
from the gastrointestinal tract so high fecal levels do occur and diarrhea is common.
• High serum and urine concentrations are achievable..
Amoxicillin
• Amoxicillin is a derivative of ampicillin that is absorbed more readily and produces less
diarrhea. It is administered orally in a dose of 20–40 mg/kg/day every 6–8 hours.
Cephalosporin drugs

• Cephalexin - ‘first-generation’, is well absorbed from the gastrointestinal tract, and can be
given in a dose of 25–50 mg/kg/day every 6 hours
• Cefaclor - ‘second-generation’ oral cephalosporin, is more active against Gram-negative
bacteria but is more expensive than cephalexin. The dosage is 20–40 mg/kg/day given
every 8 hours.
• Cefixime - ‘third generation’ , broader coverage of Gram-negative organisms, prolonged
half-life, allowing for once- or twice-daily dosage.

Quinolones
• Broader antimicrobial spectrum and special activity against Pseudomonas
aeruginosa, but in children quinolone-induced cartilage toxicity limit its use.
 Aminoglycosides
• The aminoglycosides are well tolerated by children and are of special utility in the
treatment of complicated gram-negative UTI.
• They interfere with protein synthesis by binding proteins of the bacterial ribosomes.

Gentamicin –
• Most widely used of the aminoglycosides in children and is especially effective against
Pseudomonas.
• Ototoxic (particularly to the vestibular cells) and Nephrotoxicity .

Amikacin-

• Developed to improve activity against emerging resistant strains of Pseudomonas.

Salient points regarding antibiotic use*
• when choosing empiric antibiotics, should be covered for Enterococcus because the incidence of infections
with this uropathogen is higher in early infancy than at a later age.

• A combination of ampicillin and a third-generation cephalosporin or aminoglycoside is considered a safe

empiric choice for neonates and young infants.
• Parenteral antibiotics may be converted to oral therapy in most children after several days based on culture
results and the child's clinical response.
• Most uropathogens susceptible to narrow-spectrum antibiotic as Ist-gen cephalosporins and nitrofurantoin.
• Nitrofurantoin has poor tissue penetration and should not be used for febrile UTI/pyelonephritis.
• Nitrofurantoin associated with increased risk of hemolytic anemia in infants less than 3 months of age.
• TMP is contraindicated in premature infants and newborns less than 6 weeks of age .

• Empiric broad-spectrum antibiotic is appropriate in children at risk for resistant UTI such as those with a
history of previous UTI, recent antibiotic exposure, recent hospitalization, and presence of GU anomaly.

• Sulfonamides may compete for bilirubin binding sites on albumin and cause neonatal hyperbilirubinemia
and kernicterus, so TMP-SMX is avoided during the first 6 weeks of life.
*Beetz and Westenfelder, 2011
 Management of Post-Urinary Tract Infection
• Approximately 10% to 30% of children will develop at least one recurrent UTI .

• The recurrence rate is highest within the first 3 to 6 months following a UTI .

• The more frequent and more recurrent a child's UTIs, the more likely he or she is to
experience a subsequent UTI

• For boys younger than 1 year of age, 18% will develop a recurrent infection, usually within
the following year.

• Renal scarring increases with an increasing number of febrile UTIs, with the risk going
from 5% to 10%, 20%, 40%, and 60% after the first, second, third, fourth, and fifth
pyelonephritic episodes, respectively.

• prophylactic antibiotics may be considered a nonspecific approach to the prevention of

recurrent UTIs.
 PROPHYLACTIC ANTIMICROBIAL AGENTS
• Neither NICE nor AAP recommend routine use of prophylactic antibiotics after first
febrile UTI.
• In populations known to be at higher risk for recurrent UTI, such as girls with dilating
VUR (greater than or equal to grade III), prophylactic antibiotics have proven effective
• No benefit of prophylactic antibiotics :-
-Circumcised boys,
-No bowel or bladder dysfunction,
-No recent history of UTI,
-Normal renal ultrasound or DMSA scan,
-Lack of anatomic abnormalities, and
-Nondilating VUR
• Fecal flora frequently becomes resistant to the treatment antibiotic so prophylactic
antibiotic chosen should be different than the therapeutic antibiotic used for the UTI.
Indications for Urinary Tract Antimicrobial Prophylaxis
• Vesicoureteral reflux

• Unstable urinary tract abnormality (e.g., partial urinary tract obstruction)

• Normal urinary tract but frequent reinfections

• After acute UTI awaiting radiologic evaluation

• Urethral instrumentation

• Immunosuppressed or immunocompromised status

• Infants with first UTI before 8-12 weeks of age

• Clean intermittent catheterization and vesicoureteral reflux

 Prophylactic agent
• The ideal prophylactic agent should have low serum and high urinary concentrations.

• Minimal effect on normal fecal flora, easily administered, tolerated, and cost effective.

• The potency of these antimicrobial agents is based upon the general susceptibility of
most fecal Enterobacteriaceae to these agents at urinary levels.

• The dosage is usually one fourth the normal dose, and in toilet trained children it is
routinely administered shortly before going to sleep in hopes of increasing the duration
of antibiotic within the urinary bladder.

• Common choices for prophylactic antibiotics –

TMP-SMX, TMP, nitrofurantoin, and first-generation cephalosporins.
Naturopathic treatment
• Alternative dietary or food supplements that may decrease the likelihood of UTI.

• Cranberry products inhibit fimbriated E. coli adherence and seem to decrease

bacterial biofilms, perhaps thus decreasing recurrent UTI .

• Studies in adult women show that cranberry products reduced the incidence of
UTI during a period of a year

• Studies on cranberry-product usage in children has focused upon use in children

with a neurogenic bladder, and benefit in these groups is not supported at this
time.
Probiotic
.

• Nonpathogenic and non toxogenic organisms.

• These microorganisms protect against pathogenic organisms by competitive exclusion, secretion of adhesion or
growth-inhibitory products that have antimicrobial effects, alteration of the host immune status, or contribution
to host nutritional status
• Yeast,bacilli, E. coli, enterococci,bifidobacteria,and Lactobacillus trials have variable success.

Prebiotics.
• Certain undigested portions of food, usually nondigestible carbohydrates (oligosaccharides), may be consumed
by certain gut microbiota, especially probiotic organisms, and encourage their growth. These molecules are
prebiotics.

 In the area of UTI, probiotic lactobacilli have been used to prevent necrotizing enterocolitis in infants, catheter-
related infections in spinal cord–injured patients or in children with a neurogenic bladder, and to prevent
recurrent UTI in women.
 Engineered microbes
• Microorganisms have also been used to create a “protective” interference bacteriuria
using organisms with nonvirulent features.

• The theory is that these strains will competitively inhibit more virulent or pathogenic
organisms.

• Genetically engineered E. coli that caused asymptomatic bacteriuria in another patient

into neurogenic bladders of patients on intermittent catheterization .

• Although bacteriuria occurred and symptomatic UTI decreased

Uncommon Pediatric Urinary Tract Infections
Viral Cystitis

• Acute hemorrhagic cystitis in children has occasionally been related to UTIs

caused by adenovirus-11
• Viral cystitis has commonly been identified in individuals after bone marrow
transplantation
• BK virus, a DNA virus of the polyomavirus genus, has also been found in the urine
of immunosuppressed and especially bone marrow transplant patients.
Uncommon Pediatric Urinary Tract Infections
Funguria

• Increasing in prevalence and commonly associated with recently received antibiotics or indwelling
urethral catheters.

• Predisposing factors in children include antibiotic use, prematurity, intravenous and umbilical artery
catheterization, parental nutrition, and immunocompromised state.

• Candida albicans being the most common followed by Torulopsis glabrata.

• Fungal bezoars may also form in the renal pelvis and potentially create urinary obstruction.

• Urinary alkalization and antifungal therapy may dissolve but if renal obstruction present
percutaneous or surgical removal of these fungus balls is necessary.
• To treat asymptomatic funguria, When repeated urine cultures grow greater than
10,000 to 15,000 CFU/mL, antifungal treatment is generally recommended.

• Intravesical amphotericin B bladder irrigation and oral fluconazole show that both
may clear the funguria.

• Fluconazole contraindicated in children less than 6 months of age.

 Long-Term Sequelae and follow up
• Warrant a long-term follow-up for assessment of hypertension, renal function, and proteinuria.

• Proteinuria may only be a clinical feature of CKD and may hasten its progression.

• The use of reninangiotensin antagonists may slow the progression of CKD.

• Assessment of infants and children with renal parenchymal defects should include height, weight, blood
pressure, and routine testing for proteinuria.

• Infants and children with a minor, unilateral renal parenchymal defect do not need long-term followup
unless they have recurrent UTI or family history or lifestyle risk factors for hypertension .

• Infants and children who are asymptomatic following an episode of UTI should not routinely have their
urine retested for infection.

• Asymptomatic bacteriuria is not an indication for followup