Urinary Tract Infection September 2014 Pediatric Continuity Clinic Curriculum Created by: Michelle Y. Spencer, MD

Objectives Describe the association of urinary tract infections (UTIs) and unexplained fever in infants Discuss the management of suspected UTI Review the use of radiologic studies to diagnose vesicoureteral reflux (VUR)

Case #1 A 3 m.o. male presents to acute clinic with 2 day history of tactile fever, frequent emesis and poor feeding. On exam, baby is fussy with temperature 38.4, HR 115 and BP 94/59 and no other significant abnormalities. Discussion Questions: What is the next step in evaluating this patient with fever? What are the indications for hospitalization?

What is the next step in evaluating this patient with fever? Obtain urinalysis The prevalence of UTI in febrile infants who have no obvious source is about 7-9% in those < 3 m.o. regardless of sex It decreases to 2% for males > 3 m.o. and females > 12 m.o. The “gold standard” for diagnosing UTI is the urine culture obtained by suprapubic aspiration, urethral catheterization, a ‘clean catch’ midstream specimen and bag collection (least preferable).

Interpreting the urine dipstick Nitrite test: presence of gram-negative bacteria in urine that reduce dietary nitrate to nitrite 37% sensitive and 100% specific. Positive predictive value 90% and negative predictive value 100% Leukocyte esterase test: presence of leukocytes (best performed on a fresh specimen) 73% sensitive and specific. Positive predictive value 34% and negative predictive value 95% Presence may be related to vaginal secretions, dehydration, interstitial nephritis, etc. The presence of leukocytes also may be related to vaginal secretions, dehydration, glomerulonephritis, tuberculosis or interstital nephritis and should be differentiated from a UTI

General Criteria to Diagnose UTI Suprapubic Aspiration Any growth of gram negative bacilli or > 1,000 units/ml of gram positive cocci Urethral Catheterization Greater than 50,000 colony forming units/ml for circumcised/uncircumcised males and all females Midstream Clean Catch Greater than 100,000 colony forming units/ml. These values pertain to pure, one pathogen colony growth

What are the indications for hospitalization? Infants < 3 months old should be hospitalized to receive IV fluids and antibiotics. NOTE: Each hospital might have different protocol Indications for hospitalization for older infants through adolescents: Dehydration Inability to take oral fluids Ill appearing infant or child Patients who have chronic diseases: sickle cell, diabetes, cystic fibrosis or urinary tract abnormalities Presence of perinephric abscess

Flow Chart for Evaluation & Management of UTI in Older Children and Adolescents

Case #2 A 5 y.o. female presents with 3 day history of fever and dysuria. Clean catch urine dipstick reveals spec grav 1.015, pH 6.0, positive nitrites, bacteria and leukocyte esterase. Discussion Questions: What is the most likely organism causing this patient’s symptoms? What is the most appropriate next step in management?

What is the most likely organism causing this patient’s symptoms? Escherichia coli (E. coli) accounts for up to 70% of urinary tract infections Other bacterial pathogens: Pseudomonas aeruginosa (nonenteric gram negative) Enterococcus faecalis Klebsiella pneumoniae Group B strep (predominately in neonates) Proteus mirabilis (boys > 1 y.o. and associated with renal calculi) Coag negative Staphylococcus

Other pathogens causing UTI Fungal UTI caused by Candida albicans Associated with instrumentation or the urinary tract Viral UTI caused by Adenovirus and BK virus (hemorrhagic cystitis) NOTE: In hospitalized patients the common nosocomial pathogens are E.coli, C. albicans and P. aeruginosa

What is the most appropriate next step in management? Send urine culture Start antibiotic therapy Timely appropriate treatment is helpful in preventing renal injury that may lead to scarring Cystitis Most cases 3-7 day course of antibiotics Pyelonephritis Start 10 day course of appropriate oral or IV antibiotic for initial treatment In cases of prolonged fever or renal abscess consider 14 days 3. Obtain radiologic imaging In most cases when there is appropriate antibiotic therapy cultures become sterile in 48 hours.

Appropriate Antibiotic Therapy Uncomplicated Cystitis: Choice of agents -Cefixime(Suprax) -Cefdinir(Omnicef) -Ceftibuten (Cedax) Ciprofloxacin Nitrofuratoin There is increasing resistance to Amoxicillin, Ampicillin, Trimethoprim-sulfamethoxazole (> 2 months of age), Amoxicillin-clavulanate, Cephalexin Uncomplicated Acute Pyelonephritis Similar to cystitis Ciprofloxacin 500 mg BID or extended release 1000 mg once daily Adjust antibiotic as indicated after bacterial sensitivity available.

Radiologic Imaging Fluoroscopic VCUG is the gold standard for diagnosing VUR VCUG should be done after infected urine becomes sterile or after completion of full course of antibiotics, though studies have shown that it could be done after 48-72 hours after initiation of antibiotics Renal ultrasound is safe and fast way of detecting congenital renal urinary tract anomalies that may be associated with UTI and VUR Can be obtained within 2-4 weeks of initial UTI

Indications for Ultrasonography Patients < 2 years of age with a first febrile UTI Patients of any age with recurrent febrile UTIs Patients of any age with a UTI who have a family history of renal or urologic disease, poor growth,or hypertension Patients who do not respond as expected to appropriate antimicrobial therapy

Indications for Voiding Cystourethrogram Patients of any age with two or more febrile UTIs. Patients of any age with a first febrile UTI who have any anomalies on renal ultrasound or a family history of renal or urologic disease; and children with poor growth or hypertension

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Case #3 A 2 y.o. boy presents to clinic for follow up after completing 14 day course of antibiotics for pyelonephritis. You ordered a VCUG and the results reveal bilateral vesicoureteral reflux (grade III on the right and grade IV of the left). Discussion Questions: What is the most appropriate next step in management? Which condition has strong association with UTI ?

What is the most appropriate next step in management? Start prophylactic antibiotic therapy Prophylactic dose if ¼ to ½ of the therapeutic dose Suggested Dosing TMP-SMZ 2 mg/kg daily or 5 mg/kg twice weekly Nitrofurantoin 1-2 mg/kg daily Cephalexin 10 mg/kg daily Ampicillin 20 mg/kg daily Amoxicillin 10 mg/kg daily

Vesicoureteral reflux (VUR) Occurs when urine within the bladder flows back up into the ureter and often back into the kidney. Primary concern is exposing the kidneys to infected urine → acute pyelonephritis and renal scarring All grades of VUR have potential for spontaneous resolution over a period of time. Percent resolution at 5 year follow up Grade I 82% Grade II 80% Grade III 46% Grades V 30% Grade V 13% Older age at presentation and bilateral VUR have decreased probability of spontaneous resolution VUR tends to resolve sooner in African American children

Which condition has strong association with UTI ? CONSTIPATION The association is believed to result from compression of the bladder and bladder neck Also distended colon or fecal soiling provides an abundant reservoir of pathogens Constipation in children increases the likelihood of urinary incontinence bladder overactivity, dysfunctional voiding, recurrent UTIs and persistence or progression of VUR

Other host risk factors predisposing to Urinary Tract Infection Lack of circumcision of male infants (<1 year of age) Male gender in first 6 to 8 postnatal months Lack of breastfeeding in first 6 postnatal months Constipation Dysfunctional voiding pattern Recent history of antibiotic use for any purpose Urinary tract infection in the past 6 months Indwelling catheters or intermittent catheterization Family history of recurrent urinary tract infection Recent sexual intercourse Use of a diaphragm for birth control or spermicidal agents

Management of VUR Medical management is appropriate for all stages of VUR particularly in younger children Prophylactic antibiotics, treatment of constipation and voiding dysfunction if present Surgical management is reserved for patients who fail medical management or Grade IV/V Breakthrough UTIs or persistent VUR with evidence of renal injury Close monitoring with periodic VCUG examination (yearly – to every 2 years) The time for follow up VCUG is not well defined

PREP QUESTIONS

A 4-year-old girl presents to your office for evaluation 1 month after an episode of pyelonephritis, after which she was diagnosed with grade III vesicoureteral reflux. The patient is healthy with normal growth parameters and development. She has no significant past medical history or past surgical history. According to her parents, she has been toilet trained since 18 months of age. Findings on physical examination are unremarkable; vital signs are normal. Her urine analysis in the office shows specific gravity of 1.010, pH of 6.0, and no protein, blood, leukocyte esterase, or nitrites. There is no history of urinary tract infections in the parents or the 2-year-old sister. PREP 2014 #214

evaluate the patient for voiding dysfunction Of the following, the MOST appropriate next step in the management of this patient is to evaluate the patient for voiding dysfunction order urine culture for evaluating resolution of the urinary tract infection order serum electrolytes and serum creatinine for evaluating renal function refer the patient for surgical correction of her reflux screen the 2-year-old sibling with voiding cystourethrography PREP PEARLS:A - Appropriate management of voiding dysfunction may help in spontaneous resolution of reflux and decrease risk for urinary tract infection. - More than 50% of patients experience spontaneous resolution of vesicoureteral reflux (VUR). - Lower grade of reflux, unilateral reflux, prenatal hydronephrosis, and diagnosis before age 1 year have been favorably associated with spontaneous resolution of VUR. - Current evidence does not support routine screening with voiding cystourethrogram for asymptomatic siblings of patients with reflux. - Bladder bowel dysfunction/dysfunctional elimination has been associated with recurrent infections, increased time for spontaneous resolution of reflux, and reduced success of endoscopic surgery. PREP 2014 #214

intravenous pyelography referral to urology for surgical correction A 3-month-old female infant presents to your office for follow-up of pyelonephritis diagnosed 2 months ago. After treatment of her urinary tract infection, she had a contrast voiding cystourethrogram (VCUG) that showed narrowing of the distal urethra and a normal urinary stream upon voiding (Item Q36). Her physical examination is unremarkable. She is currently on oral amoxicillin for urinary tract infection prophylaxis. Of the following, the MOST appropriate next step in the management of this patient is intravenous pyelography referral to urology for surgical correction repeat urine culture repeat VCUG in 1 year stop prophylactic antibiotics PREP PEARLS: B - Narrow urethra on voiding cystourethrogram (also termed spinning top urethral [STU] deformity) is caused by dilation of the proximal muscular urethra against a closed or narrow distal urethral sphincter. - STU has been associated with bladder dysfunction arising from contraction of the detrusor muscle of the bladder against a closed urethral sphincter. - Bladder dysfunction is common in infants; the development of normal voiding patterns is highly variable. PREP 2014 #36

Narrow urethra on VCUG (also termed spinning top urethral deformity) Narrow urethra on voiding cystourethrogram (also termed spinning top urethral [STU] deformity) is caused by dilation of the proximal muscular urethra against a closed or narrow distal urethral sphincter.

References Pediatrics in Review Article: “Urinary tract infections and Vesicoureteral Reflux in Infants and Children” (2010) AAP Clinical Guideline or Practice Parameter Nelson’s reference Harriet Lane Uptodate

BONUS PREP QUESTIONS If time permits 

A 17-year-old, sexually active boy has complaints of intermittent burning with urination for the last 2 weeks. He says he sometimes sees some staining on his underwear but has not noticed any penile discharge or genital lesions. He reports that he has never had a sexually-transmitted infection and that he always uses condoms. He is otherwise healthy and has no systemic complaints, hematuria, or urgency. On physical examination, he is at sexual maturity rating 5 for pubertal development. Other than some moistness at the urethral meatus, his genital examination findings are normal. PREP 2014 #20

Chlamydia trachomatis Escherichia coli Mycoplasma genitalium Of the following, the organism MOST likely responsible for this boy’s symptoms is Chlamydia trachomatis Escherichia coli Mycoplasma genitalium Neisseria gonorrhoeae Ureaplasma urealyticum PREP Pearls: A Dysuria and discharge in males are the most common symptoms of urethritis. Chlamydia trachomatis is the most common etiologic agent of urethritis. Treatment includes azithromycin or doxycycline. Remember to prescribe treatment for the sexual partner(s). PREP 2014 #20

A 1-year-old with genitourinary malformations recently underwent corrective urological surgery and was discharged home in stable condition with an indwelling urinary catheter. The patient presents 10 days after discharge with fever and vomiting. Physical examination is significant only for a febrile infant (40.1°C) with mild dehydration. The urine is cloudy, and a spot urine test strip analysis shows a pH of 6.0, specific gravity of 1.040, 4+ leukocyte esterase, and no nitrites, blood, or protein. The patient is admitted to the hospital parenteral antibiotics are started. PREP 2014 #72

ampicillin and ceftriaxone ceftriaxone cefuroxime and gentamicin Of the following, the MOST appropriate empiric antibiotic choice for this patient is intravenous ampicillin ampicillin and ceftriaxone ceftriaxone cefuroxime and gentamicin gentamicin PREP PEARLS :B - Empiric antibiotics in patients suspected of having enterococcal UTI should include a combination of ampicillin and third-generation cephalosporin or aminoglycoside. - Prompt treatment of patient suspected of having urinary tract infection (UTI) with appropriate empiric antibiotics is important. - Enterococcal UTI should be suspected in children with indwelling catheters and urine dipstick analysis showing negative nitrites. PREP 2014 #72

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