URINARY TRACT INFECTIONS

IN CHILDREN
Moises Auron, MD, FAAP, FACP
Assistant Professor of Medicine and
Pediatrics
Cleveland Clinic, Cleveland OH

01/17/10
Epidemiology
Children < 2 years old
 Prevalence - 7 % percent in febrile infants and young
children
 Caucasian have a 2-4 fold higher prevalence compared
with African Americans
 Girls have a 2-4 fold higher prevalence compared with
circumcised boys.
 Caucasian girls with fever ≥39ºC - 16% prevalence
 Shorter female urethra
Children > 2 years old
 Prevalence is underestimated : 8 – 9 %
 UTI are associated with urinary symptoms but in less
frequency than adults
 Higher frequency of non-specific vulvovaginitis in children
 Adults have better ability to recognize UTI symptoms

Pediatr Infect Dis J 2008; 27:302-

308 01/17/10
Epidemiology

 Age
 Boys < 1 year
 Girls < 4 years
 Circumcision
 Febrile uncircumcised infant: 4-8 fold
prevalence of UTI vs. circumcised infant

Pediatr Infect Dis J 2008; 27:302-

308 01/17/10
Pathogenesis

 Almost all UTIs are ascending in

origin (except in neonates)
 Begins with colonization of the
periurethral area by a
pathogenic bacteria and then
entry of pathogenic bacteria into
the urinary bladder

01/17/10
Microbiology

 Escherichia coli cause 80-90% of

UTIs in children
 Proteus species cause about
30% of cases of uncomplicated
cystitis in boys
 S. saprophyticus cause about
30% of UTIs in adolescents

01/17/10
Microbiology
Non-E.coli organisms: Fungal infections
 Urinary tract
malformations  Immunosuppression
 Voiding dysfunction  Long-term
 Previous antibiotic antibiotics
treatment
 Enterococci  Indwelling Foley
 Pseudomonas
 Staphylococcus aureus
 Staphylococcus
epidermidis
 Group A or B streptococcus
 Haemophylus influenzae

Arch Dis Child. 2006 Oct;91(10):845-

6 01/17/10
Uropathogenic E.
Coli
 Virulence factors
 Enhance multiplication and inflammation
 Adherence
 Pili or bacterial fimbriae that bind to
uroepithelial cells making possible contact
between tissues and toxins
 Lipopolysaccharides (O antigens or
endotoxin)
 Capsular or K antigens
 Provide resistance to serum bactericidal effect
and phagocytosis

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 Bacterial Adhesion

Transmission of a P-fimbriated E. coli adhering to a uroepithelial cell

Winberg J. Arch Dis Child (1984);59:180

01/17/10
 Host Defense
Mechanisms
 Anti-adhesive molecules
 Secretory IgA,
 Tamm-Horsfall protein
 Organic acids
 Bladder washout

01/17/10
Breast Feeding and UTI

 Anti-adhesive capacity of
secretory IgA
 Receptor analogues against
bacterial adhesion
 Promotion of a stable intestinal
flora with fewer potentially
pathogenic strains

Acta Paediatr. 2004

Feb;93(2):164-8.
01/17/10
Circumcision and UTI
 Mucosal surface of the uncircumcised
foreskin – moist surface that promotes
adhesion and replication of
uropathogenic bacterial
 Circumcised penis – keratinized skin
 Decreased meatal contamination and
bacterial ascent into the bladder
 Partial obstruction of the urethral
meatus by a tight foreskin
 NNT = 111 circumcisions to prevent
one UTI J Urol 1988 Nov;140(5):997-
1001.
01/17/10
Arch Dis Child 2005
 Circumcision and UTI
American Academy of Pediatrics:
 UTI risk: 7-14/1000 uncircumcised male < 1
y/o vs. 1-2/1000 circumcised
 Risk in uncircumcised increased 4-10 fold
 Data are not sufficient to recommend
routine neonatal circumcision

Pediatrics. 1999;
103:686-93
01/17/10
Circumcision and STD
 3 randomized trials
 HIV decreases by 53% to 60%
 HSV 2 by 28% to 34%
 HPV by 32% to 35%
 Female partners:
 Bacterial vaginosis decreases 40%
 Trichomonas vaginalis decreases 48%

Arch Pediatr Adolesc Med. 2010

01/17/10
Jan;164(1):78-84.
Urinary obstruction

 Anatomical: PUV, UPJ obstruction),

 Neurogenic (myelomeningocele)
 Functional
 Suspected when the patient has
voiding problems – enuresis,
abnormal stream, abnormal genital
examination.

01/17/10
 Voiding dysfunction

 Abnormal elimination pattern

(frequent or infrequent voids,
urgency, constipation)
 Bladder and or bowel
incontinence
 Withholding maneuvers
 Contraction of the perineal muscles
and external sphincter to prevent
incontinence results in spreading of
the contents of the distal urethra
into the bladder Pediatrics 2003
Nov;112(5):1134-7.
Urology 1991 Oct;38(4):341-4.
01/17/10
Pathogenesis
 Perineal Hygiene:
 No data associates that having girls
wipe from front to back prevents
vaginal and perineal colonization by
enterobacteria
 If fecal soiling were important in the
pathogenesis of UTIs, female infants
should have a very high incidence
prior to bowel control
Int J Antimicrob Agents. 2001
Apr;17(4):259-68.
01/17/10
 Sexual Activity and
UTI
“Honeymoon cystitis”
 Trauma to the female urethra
during intercourse forces bacteria
into the bladder.
 Spermicide use alters the normal vaginal
flora (Lactobacillus and Corynebacterium sp)
 frequent intercourse
 Treatment:
 Voiding after intercourse
 Post-coital antibiotics
Int J Antimicrob Agents. 2001
Apr;17(4):259-68.
Clin Exp Obstet Gynecol.
2005;32(3):180-2. 01/17/10
Risk Factors for HTN,
nephrosclerosis and ESRD
 Recurrent UTI
 Delay in antimicrobial treatment
 Dysfunctional voiding
 Obstructive malformations (PUV, Uretero
Vesical Junction, Uretero Pelvic Junction)
 Vesicoureteral reflux (> grade III)
 Congenital malformations (aplastic/
hypoplastic/ dysplastic kidneys)
 Young Age

Pediatr Nephrol 2000 Sep;14(10-

11):1006-10. 01/17/10
Likelihood Ratios

 L.R. 2, 5, 10 increase probability of

disease by 15%, 30% and 45%
 L.R. 0.5, 0.2, 0.1 decrease probability
of disease by 15%, 30%, 45%

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 Febrile boy 3 mo - 2 y/o
JAMA. 2007;298(24):2895-
2904

01/17/10
 Febrile girl 3 mo - 2
y/o
JAMA. 2007;298(24):2895-
2904

01/17/10
 Verbal Children > 2
y/o
JAMA. 2007;298(24):2895-
2904

01/17/10
The “three day” rule

 The infant or child with unexplained fever

should not be allowed more than 3 days
of fever without a urine examination
 Clinical and experimental data show that
delay in the treatment of pyelonephritis
increases the risk of kidney damage

Ped Clin North Am 1995:42:1433-

1457
01/17/10
Pyelonephritis (Febrile
UTI)
 Fever (Rectal T >39°C)
 Costo-Vertebral angle tenderness
 Systemic symptoms
 Elevated APR (CRP or ESR)
 Leukocytosis with bandemia
 Voiding symptoms may not be present
 Initial diagnosis
 Urinalysis + urine microscopy
 Final diagnosis
 Quantitative urinary culture

01/17/10
Cystiti
s Fever
 Urinary urgency
 Urinary frequency
 Dysuria
 New-onset nocturnal enuresis
 Foul smelling urine

01/17/10
Differential diagnosis
 In children vaccinated against H. influenzae and
S. pneumoniae:
 probability of UTI (7 %)
 probability of occult bacteremia (<1 %)
 Urinary symptoms and bacteriuria occurs in:
 nonspecific vulvovaginitis
 Nephrolithiasis
 STD (Chlamydia)
 Vaginal foreign body
 Triad of fever, abdominal pain, and pyuria:
 GAS
 Appendicitis
 Kawasaki disease
 Dysfunctional elimination
JAMA. 2007 Dec 26;298(24):2895-904.
Arch Pediatr Adolesc Med 2004
Jul;158(7):671-5. 01/17/10
Diagnosis

01/17/10
Use of “bagged” urine
 “bagged urine specimen is valid for UTI
evaluation only when there is no growth in
the urinary culture “
 5127 bagged urines vs. 2457 catheterized
specimens from infants < 24 months of age

 Contaminated specimen
 Sterile bagged specimen 62.8%
 Catheterized specimen 9.1%

J Pediatr (2000):137;221
Pediatrics 1999 01/17/10
Urinalysis: Findings for a
presumptive diagnosis of UTI

Method Findings
Bright field or Bacterial rods or
phase contrast cocci identified in
microscopy urinary sediment

Gram stain of Gram-negative

urinary rods
sediment Gram-positive
cocci
Urine dipstick Positive for nitrite
test and/or leukocyte
esterase
Infect Med 2002;19:554-60
01/17/10
Urinalysis

01/17/10
 Diagnosis

THE DEFINITIVE DIAGNOSIS

MUST BE CONFIRMED BY THE
QUANTITATIVE URINARY
CULTURE

01/17/10
 Urine
culture
Method of collection Quantitative culture: UTI present

Suprapubic aspiration Growth of urinary pathogens in

any number (exception is
<2,000 to 3,000 CFU/mL of coag-
negative Staph)
Catheterization in Febrile infants or children
females or midstream usually have >50,000 CFU/mL of
void in circumcised a single urinary pathogen.
males Infection may be present with
counts >10,000 CFU/mL (most
commonly encountered in pt
with ur. frequency)
Midstream clean void Symptomatic patients: usually
>100,000 CFU/mL of a single
urinary tract pathogen
Asymptomatic patients: at least
01/17/10 2 specimens on different
Infect Med days
Imaging Studies in UTI
 Identify anatomical abnormalities of the genitourinary tract
 Modify the risk of subsequent renal damage (surgery, antibiotic
prophylaxis).
 Imaging should be done on:
 Girls < 3 y/o with a first UTI
 Boys of any age with a first UTI
 Children of any age with a febrile UTI
 Children with recurrent UTI w/o previous imaging studies
 First UTI in a child with:
 family history of nephropathy
 abnormal voiding pattern
 poor growth
 Hypertension
 Genitourinary abnormalities

NEJM 2003; 348:195-202

Pediatrics.01/17/10
2009
Ultrasound in
UTI
 Are there two kidneys in normal location?
 ectopic, horseshoe, solitary
 Are the kidneys normal?
 Echogenicity? Size? Scars?
 Pyelonephritis (enlarged kidney)
 Lobar nephronia
 Dysplasia
 Obstruction
 Posterior urethral valves
 Uretero Pelvic Junction
 Uretero Vesical Junction
 Suggestion of VUR
 Dilatation of the collecting system
 Duplication of the urethers

Arch Dis Child 2004

May;89(5):466-8.
01/17/10
US in UTI: Other
indications
 Congenital hydronephrosis
 Palpable abdominal mass
 Abnormal urine stream
 Poor response to UTI treatment (r/o
abscess)
 Recurrent febrile UTI
 At risk for poor follow-up
 VUR

01/17/10
 Voiding Cystourethrogram
(VCUG)
 40 % of children with a first febrile UTI
have VUR
 VUR grade III – increased risk of UTI
 It may be performed as soon as the
patient is asymptomatic
 Anatomic or neurogenic abnormalities
 Bladder trabeculation
 Urethral dilatation (Spinning top
urethra)
 Residual urine volume

01/17/10
Vesicoureteral Reflux
(VUR)

01/17/10
Suggested management of boys
after first febrile UTI
 Infant or older
 Obtain an US and VCUG (important to
rule-out bladder outlet obstruction)
 If normal, suppressive antibiotic for 6
months
 Circumcision of an uncircumcised infant
 Close follow-up for a febrile UTI.
 If VUR is present, the duration of Rx is
determined by the grade, persistence
and severity of the reflux
01/17/10
Suggested management of
girls after first febrile
UTI
 Infants or older
 If there is prompt response to therapy,
no imaging studies
 Suppressive antibiotic Rx for 6 months.
 Close follow-up for a febrile UTI
 If one occurs, VCUG and US
 If VUR is present, the duration of
antibiotic Rx is determined by grade,
persistence and severity of reflux

01/17/10
VCUG: Indications
 Good response to treatment
 Afebrile > 24 hrs.
 Bacteria susceptible to antibiotic
 Voiding pattern back to baseline
 Younger infant
 No pain on urination & behavior back to
baseline
 If VCUG is not done during initial
treatment period (10 days) the child
should be on suppressive antibiotic until it
is obtained

01/17/10
 Nuclear scan - DMSA
 Dimercaptosuccinic acid (DMSA)
 Dx of acute pyelonephritis and renal scarring
 Doubtful diagnosis:
 Fever and sterile pyuria
 Acute pyelonephritis on abx who remain febrile
for > 72 hrs (detects extent of inflammation)
 Evaluation of children with VUR who have a
breakthrough infection

01/17/10
 Rx of UTI: infants < 8
wksinfants < 8 wks with (+) Cath UA
 Febrile
 Admit and administer parenteral abx
 Use appropriate neonatal abx doses
 3rd generation cephalosporin until afebrile for 24 hours
 Continue rx with therapeutic doses of an effective p.o. abx to
complete a 10–14 day course
 Continue with a suppressive abx until a VCUG is done
 Avoid nitrofurantoin in infants <1 month because of risk of
hemolytic anemia
 Avoid sulfonamides in those <2 months because of
competition with bilirubin for binding sites on albumin

01/17/10
Parenteral Antibiotic Agents
Drug Dose Frequency Comments
Ceftriaxone 50-75 (mg/kg/day) Given as a single Not suitable for Rx of
dose or divided those <6 wks of age.
every 12 hours (IV or
IM)
Cefotaxime 150 (mg/kg/day) Divided every 6-8 Also used in
hours (IV or IM) combination with
Ampicillin in infants
2-8 weeks of age
Ampicillin 100 (mg/kg/day) Divided every 8 Used in combination
hours with Gentamicin for
infants<2 weeks of
age and when
enterococcus is
suspected

Gentamicin Full term neonates Every 12-18 hours Used in combination

<7 days old (2.5 (depending on with Ampicillin. Blood
mg/kg/dose) weight) levels and kidney
function if therapy
Term infants >7 days Every 8 hours
extends >48 hours.
old and children <5
yr (2.5 mg/kg/dose)

01/17/10 Infect Med 2002;19:554-60

Children >5 yr old (2- Every 8 hours
 Oral Antibiotic Agents
Antibacterial Agent Daily dose and intervals
Trimethoprim/sulfamethoxazole 6-12 mg/kg TMP, 30-60 mg/kg/d
(TMP/SMX) SMX in divided doses q12h
Amoxicillin 25-50 mg/kg in divided doses
q12h
Amoxicillin and Clavulanic acid 25-45 (Amoxicillin component)/kg
per day in divided doses q12h

Cephalexin 20-50 mg/kg in divided doses of

q6h
Cefixime 8 mg/kg in divided doses q12h
Cefpodoxime 10 mg/kg in divided doses q12h
Loracarbef 15-30 mg/kg in divided doses
q12h
Nitrofurantoin 5-7 mg/kg in divided doses q6h
Infect Med 2002;19:554-60
01/17/10
Febrile UTI Rx: 2 mo to 2
y/o
 If immediate antibiotic treatment is
indicated
 Urine should be obtained by suprapubic
aspiration or bladder catheterization

 Suprapubic aspiration is necessary for

 Male with a tight foreskin
 Girl with marked labial adhesions
 Any child with a severe perineal rash

Pediatrics
1999:103:843-852
01/17/10
Febrile UTI Rx: 2 mo to 2
y/o
 UA - positive for a UTI
 Prompt parenteral antibiotic Rx has
usually been recommended
 Daily IM or IV treatment until afebrile
and clinically improved
 Hospitalize toxic or dehydrated child

Pediatrics
1999:103:843-852
01/17/10
Febrile UTI Oral Rx: 1 mo to 2
y/o
 RCT (N=306 febrile infants)
 153 = IV cefotaxime (3d) PO cefixime (11d)
 153 = PO cefixime (14d)
 No difference in the short or the long term outcome
(clinical response, reinfection, renal scars at 6 Months)

Pediatrics
1999;104:79-86
01/17/10
P.O. Rx of pyelonephritis:
Suggested criteria
Oral antibiotics
 2nd or 3rd generation cephalosporin
 Amoxicillin/clavulanate
 Co-trimoxazole (TMP/SMX)
 The child should be non-toxic
 No vomiting should be present
 Close follow-up is expected

Curr Opin Pediatr (2004):16:85-88.

01/17/10
 Rx of Febrile UTI in > 2
y/o
 Complicated pyelonephritis
 High fever, acutely ill or toxic
 Persistent vomiting
 Moderate to severe dehydration
 Poor compliance anticipated
 Hospitalize
 IV fluids and abx until afebrile for 24 hrs
 Outpatient treatment to complete 10 to 14
days with therapeutic doses of p.o. abx

01/17/10
 Rx of Febrile UTI in > 2
y/o
 Uncomplicated pyelonephritis
 Febrile, but not acutely ill
 Able to take p.o. fluids & medications
 Mild dehydration
 Good compliance anticipated
 Rehydrate as an outpatient prn.
 Oral or IV antibiotic
 Repeat IV or IM Rx in 24 and 48 hrs if fever persists
 Complete 10 to 14 days of Rx with therapeutic doses of oral antibiotic

01/17/10
Cystitis: Rx
 Mild symptoms
 Supportive care until culture report
 Moderate or severe symptoms
 Oral antibiotic and supportive care
 Supportive care
 High fluid intake
 With severe voiding symptoms,
phenazopyridine (for no longer than 2 days)

01/17/10
Cystitis: Rx
 Optimal duration of antibiotic Rx

 No difference between 2–4 days and 10-14

days of oral treatment in the number of
children with bacteriuria at the end of
treatment or in recurrences after 1 and 15
months
 Single dose or single day treatment -
unsatisfactory

The Cochrane Library 2005;2:1-25

01/17/10
Satisfactory response to
Rx:
 Child afebrile after 48 to 72 hrs of Rx
 Voiding pattern has returned to that
present prior to Dx of febrile UTI
 Younger infant appears to have no
pain on urination and behavior is
generally back to normal

01/17/10
 Suppressive Antibiotic
Rx
 After a 1st febrile UTI - 30% of children will
have a recurrence in 1 year
 Risk greatest within 2 – 6 months after UTI
 No VUR or Grade I – II VUR
 No support for Abx to prevent reinfection or
renal scarring

01/17/10
 Recommendations for
Suppressive Antibiotics
 Children with VUR > Grade III are at risk
for recurrence of UTI
 Young infants have very distensible collecting
systems in which marked VUR is often
reversible over 1 – 3 years
 They “may” benefit from suppressive antibiotic
 Rx for 18 – 24 months
 In absence of recurrence of a febrile UTI,
follow-up VCUG after 24 months

01/17/10
 Cranberries and UTI
 Used to treat and prevent UTIs before the discovery of antibiotics
 For decades cranberry-derived beverages have been thought to
reduce the incidence of bladder infections
 Facts
 Decrease of urinary pH, but not enough to keep below 5.5
 Increased hippuric acid production (but levels not great enough
to cause bacteriostasis)
 Prevention of bacterial adherence of uropathogens in urine
 Fructose - interfere with adhesion of type 1 fimbriated E. coli
to uroepithelium
Proanthocyanidins - inhibit adherence of P-fimbriated E. coli
 High oxalate content

J Urol 1984 May;131(5):1013-6

N Engl J Med 1998 Nov
01/17/10
5;339(19):1408