Urinary Tract Infection/Enuresis

Educational Objectives

The goal of this program is to improve the management of pediatric urinary tract infections (UTIs) and enuresis. After hearing and assimilating this program, the clinician will be better able to:

1.   Tailor evaluation and treatment of UTIs to specific patients.

2.   Describe current strategies for treating UTIs.

3.   Choose appropriate diagnostic imaging for children with recurrent UTIs.

4.   Identify the various etiologies of enuresis.

5.   Explain to family members the impact and importance of positive reinforcement in successful treatment of
enuresis.

Faculty Disclosure

In adherence to ACCME Standards of Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Howard is the President of Total Child Health, Inc. Dr. Erhard and the planning committee reported nothing to disclose. In their lectures, Drs. Erhard and Howard discuss the off-label or investigational use of therapies, products, or devices.

Acknowledgments

Dr. Howard spoke in Amelia Island, FL, at Pediatrics for the Primary Care Physician, presented June 26-28, 2009, by Nemours Childrens Clinic. Dr. Howard spoke in Miami Beach, FL, at Masters of Pediatrics 2008 Leadership Conferences: Exploring Contemporary and Future Pediatrics, presented January 28 to February 2, 2009, by the University of Miami Leonard M. Miller School of Medicine, Departments of Pediatrics and Dermatology and Cutaneous Surgery. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production in this program.

Pediatric Urinary Tract Infection:What’s Important

Michael J. Erhard, MD, Division Chief, Department of Surgery, Division of Pediatric Urology, Nemours Chil­drens Clinic, Jacksonville, FL

Description: urinary tract infection (UTI)  —  inflammation of urinary tract caused by infectious agent; urinary tract (UT)  —  from cortex of kidney, through renal pelvis, ureter, and urethra

Epidemiology: <1 yr of age  —  2.5 to 4 times more likely in boys than in girls; more common in uncircumcised boys than in circumcised boys; >1 yr of age  —  risk greater in girls for anatomic reasons (eg, shorter urethra); common pediatric diagnosis; whites at greater risk than other ethnicities

Risk factors: previous UTI  —  »25% of infants reinfected at older age; 40% to 60% of girls have repetitive UTIs; im­munosuppressive states  —  chemically induced (by, eg, corticosteroids, immunosuppressive agents); physically in­duced by disease states (eg, diabetes); anatomic abnormalities of UT  —  blockages; abnormal valves; high-grade reflux, in which postvoid residual travels from kidney to bladder; functional abnormalities of UT  —  incomplete or abnormal emptying due to neurogenic or behavioral issues; urologic instrumentation  —  hospital-acquired UTIs from catheters; catheterized testing; sexual activity  —  sexual debut; intact foreskin  —  increases risk throughout life

Microbiology: uncomplicated UTIs  —  80% to 85% caused by Escherichia coli; characterized by dysuria and abnor­mal urinary frequency related to effects on lower UT (bladder, and urethra); complicated UTIs  —  caused by same pathogens, but with more severe illness (eg, pyelonephritis)

Pathophysiology: intestinal flora colonization  —  in infants and uncircumcised boys; introitus or inner prepuce colo­nized by bacteria, which ascend urethra and cause humoral and cellular inflammatory responses; terminal fimbriae of bacteria adhere to urothelium; attachment promotes growth and replication; cranberry effective in preventing ad­herence; P fimbriae in E coli  —  allow mobility; E coli invade kidneys by traveling up ureter, resulting in pyelone­phritis in patients without reflux; 40% of children with febrile UTI diagnosed with reflux

Diagnosis based on history: infants and nonverbal children  —fever, irritability, poor feeding, or new nocturnal or di­urnal enuresis in toilet-trained child; verbal children  —  dysuria (burning sensation; may be due to vulvovaginitis); lower abdominal pain (rule out constipation); presence and severity of fever  —  in infants, quick response to antibi­otics indicates minimal febrile UTI without pyelonephritis; additional history  —  previous UTIs; prenatal history (eg, abnormal ultrasonography [US]); previous genitourinary (GU) surgery; family history of GU infections or ure­thral dilatation

Dysfunctional elimination: combination of dysfunctional urinary and bowel habits; signs  —  infrequent voiding (be­havioral, eg, holding urine, refusal to urinate, lack of toilet access); frequent urination due to constipation; diurnal and nocturnal enuresis; urge incontinence, caused by delayed voiding or irritability from stretching of bladder due to constipation; solutions  —  teach to void regularly; resolve constipation with laxatives (eg, polyethylene glycol 3350 [eg, MiraLAX], magnesium hydroxide [eg, Milk of Magnesia]); recognition of problem eliminates need for urethral dilatation

Diagnosis by physical exam: nonspecific in infants; abdominal or flank pain; external genitalia  —  look for labial ad­hesions; check for circumcision; examine meatus; examine scrotum for testicular swelling to rule out epididymitis and epididymo-orchitis

Diagnostic tests: urinalysis  —  in-office dipstick analysis or microscopy; microscopy more specific and sensitive than dipstick analysis; leukocyte esterase 75% sensitive and specific; nitrites (produced by Gram negative bacteria) have low sensitivity, but »100% specific; on microscopy, >10 white blood cells (WBCs) per high-power field (HPF) on unspun specimen or >5 WBCs per HPF on spun specimen predictive; specimen on Gram stain more specific than positive dipstick; positive leukocyte esterase and nitrite more predictive together than either alone; cannot make di­agnosis on dipstick or urinalysis alone; urine culture  —  gold standard; >100,000 colony-forming units (CFU) per milliliter for voided specimen and >10,000 CFU/mL for suprapubic aspirate specimen diagnostic; depending on other findings, lower CFU/mL may be significant; collection methods (most to least accurate)  —suprapubic aspi­rate; catheterized urine; midstream collection in circumcised boys and older girls; bagged collection (>50,000 CFU/mL probably diagnostic if cultures yield single organism; follow up with catheter specimen; finding of mixed flora indicates contamination)

Radiographic imaging: controversial; no appropriate algorithm; considerations before work-up  —  febrile vs nonfe­brile illness; sex (consider severity and frequency in girls); age; one vs multiple UTIs; in girls at sexual debut, coun­sel about sexual behavior before work-up; with inadequacy of response to treatment (eg, persistent fever), evaluate for anatomic abnormalities via urgent US

Vesicoureteral reflux (VUR): American Academy of Pediatrics recommends evaluating children 2 mo to 2 yr of age with UTI for VUR at earliest convenient time

Ultrasonography: evaluation  —  size, shape, and abnormalities of kidney and bladder; hydronephrosis; bladder thick­ness and obstructions, particularly in boys; noninvasive; radiation-free; alters treatment in 4% to 5% of patients

Voiding cystourethrogram (VCUG): invasive; involves catheterization of bladder; fluoroscopic  —  current tech­niques allow tailoring of dose of radiation (persistent fluoroscopy or radioisotopes used in past gave higher expo­sure); provides superior anatomic imaging and VUR grading, compared with radioisotopes; radioisotopic cystogram  —  difficult to obtain; time-intensive; rarely used by speaker; midazolam (eg, Versed) and hypnosis pos­sibly helpful in calming patients

Dimercaptosuccinic acid (DMSA) scintigraphy: radioisotope retained within cortex of kidney; good sensitivity and specificity for detection of acute pyelonephritis and for renal scarring (occurs in 8% of pediatric UTIs); radiation exposure relatively high in kidneys, but minimal to ovaries and bone marrow; advocated in Europe as first-line im­aging (“top down” approach); not readily available at present; possible findings  —  disparate kidney size (may be re­nal dysplasia or hypoplasia, rather than true scarring); scarring in pyelonephritis appears as “cold spot” (in acute pyelonephritis, DMSA unable to enter inflamed areas, resulting in white areas on image); pyelonephritis and result­ing scarring typically found at upper and lower poles of kidneys; comparison with US  —  US sufficient to show sig­nificant scarring; however, viewing of kidneys in 3-dimensional configuration possible with DMSA, thus allowing detection of defects hidden in purely anterior-posterior perspective

Treatment: controversial; outpatient vs inpatient care  —  treat infants with high temperatures as inpatients and older children as outpatients; assess level of toxicity and issues of parental compliance; antibiotics  —  type and length of course depends on patient age and symptoms; appropriate to start while awaiting culture results; antibiotic guidelines  —  age <2 mo, intravenous (IV) ampicillin, IV gentamicin, and third-generation IV cephalosporins; age >2 mo, third-generation cephalosporins; longer course of oral or IV antibiotics for age <2 yr; use of fluoroquino­lones (eg, oral ciprofloxacin) off-label, but well-supported by literature; uncomplicated UTIs  —  3 to 5 days of oral antibiotics sufficient for school-age children with uncomplicated UTIs (possibly £3 days, depending on age); pro­phylaxis recommended for children with VUR or with current UTIs while resolving behavioral issues (eg, incom­plete voiding); trimethoprim (eg, Primsol) effective for uropathogens and avoids possible allergic reactions seen when combined with sulfamethoxazole (eg, Septra, Bactrim); complicated UTIs  —fluoroquinolones; aminoglyco­sides (eg, gentamicin); third-generation cephalosporins; evaluate for urinary abnormalities

Conclusions: urine culture remains gold standard and suggested for every evaluation (even with positive dipstick); as bacterial resistance patterns change, obtaining sensitivities through culture important for providing adequate treat­ment

Enuresis

Barbara J. Howard, MD, Assistant Professor of Pediatrics, Johns Hopkins University School of Medicine, Bal­timore, MD

Definition of enuresis: involuntary loss of urinary continence in individual with mental age ³5 yr; wetting  ³2 times per week for 3 mo or causing distress or impairment; not due to substances or medical condition

Impact of enuresis: associated with significant distress and lowered self-esteem; creates burden, cost, and anger in family; may indicate psychosocial or physical problems; readily managed in primary care setting

Persistence of enuresis: seen in 7% of boys and 3% of girls 5 yr of age; 3% of boys and 2% of girls 10 yr of age; »1% of 18-yr-olds; 1 in 6 stop wetting every year after 5 yr of age; culturally dependent

Types of enuresis: normal  —  20% relapse  ³1 time after 6 yr of age; primary  —  small bladder capacity; more likely to have family history of enuresis; more frequent urination; fewer psychiatric symptoms; secondary  —  recurrence of wetting after being dry for »6 mo; more girls affected; psychiatric symptoms (eg, stress, anxiety) common; diurnal  —  more likely to have UT abnormalities (if >5 yr of age), soiling, giggle micturition, and behavioral prob­lems; polysymptomatic  —  multiple episodes; have early signs of voiding problems (difficulty detecting urge, need reminders, have daytime wetting and soiling and/or GU abnormalities); more difficult to treat

Genetic factors: 77% risk for enuresis if both parents enuretic; 43% with one parent; 15% with no enuretic parents

Cultural differences: 80% of participants in Cambridge, MA, study (mostly middle-class, white) dry by 3 yr of age; in Sweden, 97% dry by 5 yr of age; in the United States, percentage dry at 5 yr of age differs between ethnicities; enuresis more likely in lower socioeconomic classes than upper classes, perhaps due to psychiatric or developmen­tal issues

Arginine vasopressin rhythm defect: attenuated rhythm and lower circadian plasma arginine vasopressin levels ob­served in girls with enuresis; largest nocturnal urine excretion and most pronounced arginine vasopressin defi­ciency in desmopressin responders; greater urine output on nights with enuresis related to increased sodium excretion

Constipation: noted in 30% of children with enuresis; pressure from bolus of stool stimulates sacral nerves to relax pelvic muscles and release urine; successfully treating encopresis usually cures enuresis; UTIs common in girls with encopresis

Sleep apnea: daytime sleepiness; snoring; restlessness during sleep; may cause attention deficit-hyperactivity disor­der (ADHD); increases brain natriuretic peptide; mild increases in sleep pressure raise arousal threshold and pro­mote enuresis

Central nervous system: mental retardation; breastfed children half as likely to have enuresis; valproic acid for sei­zures; 41% of children with ADHD and »21% of those with bipolar disorder have enuresis; also associated with learning disorders and other developmental issues; lower spinal defect  —  look for tethered cord, particularly with onset of enuresis in older child; check anal wink and ankle deep tendon reflexes (DTR)

Endocrine: diabetes mellitus and insipidus; hyperthyroidism, due to lack of increased ADH at night; renal tubular ac­idosis; growth abnormalities may indicate endocrine etiology

Urinary tract infections: frequent enuresis predictive of UTIs; 45% of girls with bacteriuria and 17% without are enuretic; perform urine culture in girls; present in 5% of nocturnal enuretics and 25% of diurnal and nocturnal en­uretics

GU anomalies: found in 75% of adolescents and 43% of diurnal enuretics >5 yr old; likelihood of structural anomaly increases with age; signs of lesions  —  constant dribbling indicates ectopic ureter or ureterocele; abnormal stream indicates stitch in urethra and stenosis; trouble initiating void; daytime urgency or frequency; dysfunctional voiding (eg, need to squat); concentrating defect due to sickle cell disease, renal failure, or diuretics; smaller bladder capac­ity

Other etiologies: parasites (eg, pinworms); vulvovaginitis

Evaluation: history  —  day or night; giggle micturition; post-void; stream; effort; need for reminders; signs of urge; UTI; time of occurrence; times per week; amount per void; longest dry period; stool frequency less than every other day; soiling; constipation; sleep conditions; sleep apnea; daytime sleepiness; family history; parental attitudes; sib­ling and peer attitudes; developmental history; social stresses; examination  —  general physical; DTR and anal wink; abnormal stream; meatus; soiling; behavior; tests  —  urinalysis and urine culture in girls; no standard blood tests or x-rays; US and VCUG only with abnormal urine, adolescent, multiple UTIs, or diurnal enuretic >5 yr of age failing treatment

Management: support child; educate on bladder and bladder capacity; bedtime routine (ie, void before bed, warm and dry bed, sleep alone, place towel over wet spots); no caffeine; reward chart for awakening to void, smaller spots, as well as dry beds; avoid punishment; conditioning  —  if time of void regular, set alarm for one-half hour pre-void (77% success); or, parent awakens child and brings to toilet 2 to 3 hr after bedtime (62% success); for di­urnal enuresis, take child to void every 2 to 3 hr; reward cooperation; consequence for resistance or wetness

Nocturnal alarm: conditions bladder sensation to sphincter tightening; 80% improve in 8 to 10 wk; 10% to 15% re­lapse, but 50% remain improved and 30% cured with retraining; after multiple dry nights, force 2 to 4 cups of fluids at bedtime and reward success; after 2 wk of success, turn off alarm 1 of 3 nights; risk factors for relapse  —  mother with negative attitude; poor housing; family problems; behavioral problems; more frequent wetting

Medication: desmopressin  —  expensive; available in 100- to 400-μg tablets that dissolve in mouth (MELT); lower risk of water intoxication when taken orally (intranasal spray no longer recommended); risk factors for hyponatre­mia include >8 oz evening fluid intake, exceeding recommended dose, and age <6 yr; imipramine  —  25- to 50-mg tablets; side effects include rash, sleep and mood problems, and liver issues; deadly in overdose; perform baseline EKG; tolterodine  — a-cholinergic; not sufficient alone; supports effect of desmopressin in diurnal enuresis; atom­oxetine (Strattera)  —  off-label use; reduces wet nights

Suggested Reading

Austin PF et al: Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind placebo-controlled trial. Pediatrics 5:122; 2008; Bratslavsky G et al: Recurrence risk in infants with urinary tract infections and a negative radiographic evaluation. J Urol 4:172, 2004; Chi A et al: Urinary tract infection following successful dextranomer/hyaluronic acid injection for vesicoureteral reflux. J Urol 5:179, 2008; Craig JC et al: Antibiotic prophylaxis and recurrent urinary tract infection in children. N Engl J Med 18:361, 2009; Gauthier M et al: Treatment of urinary tract infections among febrile young children with daily intravenous antibiotic therapy at a day treatment cen­ter. Pediatrics 4:114, 2004; Hagstroem S et al: Bladder reservoir function in children with monosymptomatic nocturnal enuresis and healthy controls. J Urol 2:176, 2006; Huang DT et al: Clinical differentiation of acute pyelonephritis from lower urinary tract infec­tion in children. J Microbiol Immunol Infect 6:40, 2007; Kwak KW, Park KH: Clinical inconsistency of lower urinary tract symp­toms between questionnaire and bladder diary in children with nocturnal enuresis. J Urol 3:180, 2008; Lee HY et al: The efficacy of ultrasound and dimercaptosuccinic acid scan in predicting vesicoureteral reflux in children below the age of 2 years with their first fe­brile urinary tract infection. Pediatr Nephrol 10:24, 2009; Lin CY et al: Risk factors of ciprofloxacin resistance in urinary Escherichia coli isolates. J Microbiol Immunol Infect 4:41, 2008; Lottmann H et al: Long-term desmopressin response in primary nocturnal en­uresis: open-label, multinational study. Int J Clin Pract 1:63, 2009; Marcus N et al: Non-Escherichia coli versus Escherichia coli community-acquired urinary tract infections in children hospitalized in a tertiary center: relative frequency, risk factors, antimicrobial resistance and outcome. Pediatr Infect Dis J 7:24, 2005; Rittig S et al: The circadian defect in plasma vasopressin and urine output is related to desmopressin response and enuresis status in children with nocturnal enuresis. J Urol 6:179, 2008; Roth CC et al: Occur­rence of urinary tract infection in children with significant upper urinary tract obstruction. Urology 1:73; 2009; Stauffer CM et al: Family history and behavioral abnormalities in girls with recurrent urinary tract infections: a controlled study. J Urol 4:171, 2004; Zink S et al: Behavioral comorbidity differs in subtypes of enuresis and urinary incontinence. J Urol 1:179; 2008.