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


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

 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

 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

 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


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


Bacterial Adhesion

Transmission of a P-fimbriated E. coli adhering to a uroepithelial cell
Winberg J. Arch Dis Child (1984);59:180

Host Defense Mechanisms  Anti-adhesive molecules
 Secretory IgA,  Tamm-Horsfall protein  Organic acids

 Bladder washout


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.


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.

 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.

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%


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


JAMA. 2007;298(24):28952904

Febrile girl 3 mo - 2 y/o


JAMA. 2007;298(24):28952904

Verbal Children > 2 y/o


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

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


Cystiti s Fever
    

Urinary urgency Urinary frequency Dysuria New-onset nocturnal enuresis Foul smelling urine


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



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





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

 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


 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


Vesicoureteral Reflux (VUR)


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

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

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

 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


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


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.


150 (mg/kg/day)


100 (mg/kg/day)

Divided every 8 hours


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)

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

Cephalexin Cefixime Cefpodoxime Loracarbef Nitrofurantoin

Febrile UTI Rx: 2 mo to 2 y/o
 If immediate antibiotic treatment is


 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

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

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

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.

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


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


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)


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


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


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


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


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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