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UTI in Children

UTI in Children

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Lecture about epidemiology, diagnosis and treatment of Urinary Tract Infections in Pediatrics.
Lecture about epidemiology, diagnosis and treatment of Urinary Tract Infections in Pediatrics.

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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; 27:30201/17/10 308

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; 27:30201/17/10 308

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:  Urinary tract malformations  Voiding dysfunction  Previous antibiotic treatment
Enterococci Pseudomonas Staphylococcus aureus Staphylococcus epidermidis  Group A or B streptococcus  Haemophylus influenzae
   

Fungal infections  Immunosuppression  Long-term antibiotics  Indwelling Foley

Arch Dis Child. 2006 Oct;91(10):8456 01/17/10

Uropathogenic E. Coli factors  Virulence
 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

01/17/10

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):9971001. 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 Pediatrics 2003 into the bladder

Nov;112(5):1134-7. 01/17/10 Urology 1991 Oct;38(4):341-4.

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(1011):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%

01/17/10

Febrile boy 3 mo - 2 y/o
JAMA. 2007;298(24):28952904

01/17/10

JAMA. 2007;298(24):28952904

Febrile girl 3 mo - 2 y/o

01/17/10

JAMA. 2007;298(24):28952904

Verbal Children > 2 y/o

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 1995:42:14331457
01/17/10

Pyelonephritis (Febrile UTI) (Rectal T >39°C)  Fever
     

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  Catheterized specimen

62.8% 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 Method of collection culture

Quantitative culture: UTI present

Suprapubic aspiration Growth of urinary pathogens in any number (exception is <2,000 to 3,000 CFU/mL of coagnegative Staph) Catheterization in females or midstream void in circumcised males Febrile infants or children usually have >50,000 CFU/mL of a single urinary pathogen. 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 2 specimens on different days 01/17/10 Infect Med

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. 2009 01/17/10

Ultrasound in  Are there UTIectopic,two kidneys in normal location?  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

 Congenital hydronephrosis  Palpable abdominal mass  Abnormal urine stream  Poor response to UTI treatment (r/o

US in UTI: Other indications

abscess)  Recurrent febrile UTI  At risk for poor follow-up  VUR

01/17/10

 40 % of children with a first febrile UTI      

Voiding Cystourethrogram (VCUG)
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

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

 No pain on urination & behavior back to

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 wks  Febrile infants < 8 wks with (+) Cath UA
 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 Ceftriaxone Dose 50-75 (mg/kg/day) Frequency Comments Given as a single Not suitable for Rx of dose or divided those <6 wks of age. every 12 hours (IV or IM) Divided every 6-8 hours (IV or IM) Also used in combination with Ampicillin in infants 2-8 weeks of age Used in combination with Gentamicin for infants<2 weeks of age and when enterococcus is suspected Used in combination with Ampicillin. Blood levels and kidney function if therapy extends >48 hours.

Cefotaxime

150 (mg/kg/day)

Ampicillin

100 (mg/kg/day)

Divided every 8 hours

Gentamicin

Full term neonates <7 days old (2.5 mg/kg/dose)

Every 12-18 hours (depending on weight)

Term infants >7 days Every 8 hours old and children <5 yr (2.5 mg/kg/dose)
01/17/10

Children >5 yr old (2- Every 8 hours

Infect Med 2002;19:554-60

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 Amoxicillin and Clavulanic acid 25-50 mg/kg in divided doses q12h 25-45 (Amoxicillin component)/kg per day in divided doses q12h 20-50 mg/kg in divided doses of q6h 8 mg/kg in divided doses q12h 10 mg/kg in divided doses q12h 15-30 mg/kg in divided doses q12h 5-7 mg/kg in divided doses q6h Infect Med 2002;19:554-60
01/17/10

Cephalexin Cefixime Cefpodoxime Loracarbef Nitrofurantoin

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 (N=306 febrile infants)  RCT
 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  Mild dehydration  Good compliance anticipated  Able to take p.o. fluids & medications

 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

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