I. Epidemiology

  1. Lifetime incidence = 5% of girls; 1-2% of boys.
  2. In < 1yo, more frequent in boys than girls; in > 1yo; more common in girls
  3. Higher in LBW infants

II. Etiology/pathogenesis

  1. E. coli accounts for > 80%
  2. Also Proteus, Staph, strep, Enterobacteriaciae, and occasionally Candida albicans
  3. Predisposing factors--anything that promotes urinary stasis
  1. Kidney stones
  2. Obstruction from other causes, e.g. extrinsic masses
  3. Ureterocoeles
  4. Vesicoureteral reflux (VUR)
    1. Prevalence 18-40% in kids w/UTI (though these figures are from studies that mostly looked at tertiary referral populations)
    2. Diagnosis:
      1. Voiding cystourethrogram (VCUG)--Can identify severity of VUR as well as anatomic abnormalities; high radiation dose
      2. Isotope cystogram--More sensitive for VUR than VCUG and less radiation, but doesn't reveal urethral abnormalities, so not a good choice for male pts
    3. Graded I-V; grades I-II often tx'd w/abx prophylaxis (see below) and scheduled voiding; grades III-V often tx'd with surgically
    4. In an observational study of 149 children with grade III-IV VUR on abx prophylaxis followed for 10y, persistence of VUR at the same level of severity was seen in 48% of kids at 5y and 23% at 10y; complete resolution of VUR was seen in 14% at 5y and 52% at 10y (J. Peds. 139:620, 2001--JW)
  1. Voiding dysfunction
    1. A general term encompassing a variety of patterns of detrusor instability and incomplete bladder emptying. Often accompanied by daytime enuresis and constipation
    2. Dx'd with urodynamics
    3. Treatment
      1. Timed voiding
      2. Prophylactic antibiotics
      3. Anticholinergics, e.g. oxybutynin
      4. Biofeedback
  1. Duplicate collecting systems
  2. Urethral abnormalities in males
    1. Posterior urethral valves
    2. Urethral diverticula

III. Clinical presentation

  1. "Irritative symptoms"--Enuresis, dysuria, urinary frequency
  2. Malodorous urine, gross hematuria
  3. Suprapubic pain
  4. Sx suggesting pyelonephritis:
    1. Fever
    2. Vomiting
    3. Flank pain
    4. Sepsis

IV. Complications/Sequalae

  1. Renal parenchymal scarring, leading to Hypertension or Renal Failure
    1. Renal scarring may occur in 10-15% of kids with UTI
    2. More likely in kids < 1yo
    3. Risk of ESRD in pts with renal scarring after UTI about 10% over 27y in one series
    4. Renal scarring can occur with VUR w/o any h/o UTI, so causal association w/UTI is unclear

V. Evaluation of a patient with UTI

  1. To confirm diagnosis
    1. Urinalysis (in girls, > 5 WBC/HPF is abnormal)
    2. Urine culture
      1. < 1yo, get it from cath or suprapubic aspirate
      2. > 1y, clean-catch OK
      3. "Bagged" urine tend to results in high false-positive culture rate and AAP advises against as of 4/99
      4. In a prospective study in 192 children < 3yo with unexplained fever and abnormal urinalysis from bag-obtained specimen, all of whom had urine collected both by a bag and by catheter, catheter-obtained specimens were positive in 53% of children vs. 48% of children with the bag; contamination occurred in 8% of catheter-obtained specimens vs. 30% of bag-obtained specimens (J. Pediatr. 154:803, 2009-JW)
      5. Criteria for diagnosis of UTI
        1. Suprapubic aspirate--any growth
        2. In & out cath'd specimen--> 1,000 CFU/ml
        3. Voided urine--> 100,000 CFU/ml
      6. Consider contamination if > 1 organism grows
  1. To identify underlying causes and/or renal failure from previous renal parenchymal damage:
    1. BP
    2. Check for palpable bladder (may indicate neurogenic bladder dysfunction)
    3. Abdominal/flank mass (extrinsic mass causing ureteral obstruction)
  1. Diagnostic imaging after diagnosis of first UTI in children
    1. Somewhat controversial
      1. The idea is to identify underlying factors that would predispose to future UTI's and renal parenchymal damage, amenable to prophylactic abx or to surgery
      2. Little data as to the clinical impact of imaging studies as of 2003
    2. Renal ultrasound
      1. Can identify hydronephrosis, structural abnormalities, and calculi
      2. Not highly sensitive for VUR, renal scarring, or renal inflammatory changes
      3. If abnormal, many recommend following with renal scintigraphy.
    3. Renal cortical scintigraphy
      1. Usually with Technetium-99-dimercaptosuccinic acid (DMSA) or -glucoheptonate (the latter of which, unlike DMSA, shows collecting system as well as kidneys)
      2. More sensitive than u/s for renal scarring and pyelonephritis
      3. Doesn't image the collecting system and can't identify obstruction well
      4. Ultrasound and DMSA scintigraphy both had poor sensitivity (48% and 76%,. respectively) for detecting severe VUR (compared with VCUG) in a study in 296 children < 2yo with first febrile UTI (Pediatrics 126:e513, 2010-JW)
    4. Voiding cystourethrogram (VCUG)
      1. Best test for detecting VUR but shouldn't be done in acute setting of infection b/c infection may cause transient VUR!
      2. Also good for identifying urethral abnormalities in males
    5. IV Urography (aka IV pyelography, "IVP")
      1. Less sensitive than u/s renal & cortical scintigraphy for renal scarring or pyelonephritis
      2. Risk of reaction to IV contrast, so largely replaced by u/s renal & cortical scintigraphy
    6. CT of kidneys--Sensitive & specific for acute pyelonephritis
    7. Isotope cystogram
      1. Like VCUG but instead of contrast, radiolabeled tracer is used; less radiation than VCUG
      2. May be more sensitive for VUR than VCUG
    8. What test/tests to do?
      1. Traditional approach has been ultrasound and VCUG in all children
        1. For girls > 5yo, imaging w/u often deferred to 2nd UTi
      2. AAP as of 4/99 recommends u/s and (either VCUG or renal cortical scintigraphy) for kids 2mo-2yo
      3. However, in a case series of 50 kids 2mo-5yo hospitalized with acute pyelo, nearly all of whom had VCUG, u/s, and renal cortical scintigraphy, 97% of abnormal kidneys were identified on just VCUG + renal cortical scintigraphy alone (the missed ones were both findings of possible acute pyelonephritis); scintigraphy + u/s would have had a sensitivity of only 94% (J. Peds. 127:373, 1995)

VI. Treatment

  1. Indications for initiating tx w/IV abx:
    1. Sign/sx of pyelonephritis (high fever, severe flank pain, toxic appearance)
    2. < 3mo
    3. Note that fever may take 3-5d to resolve after initiation of tx
    4. After defervescence, custom is to tx with PO abx x 10-14d
  2. Outpt PO abx as good as inpt IV abx for children 1-2yo in one randomized study (cefixime x 14d, 97% had E. coli; Peds 104:79, 1999--JW)
  3. Duration of treatment
    1. In a meta-analysis of 22 studies with total 1279 pts comparing short-course (1 dose-3d) vs. conventional-course (> 4d) tx for uncomplicated UTI in pts < 18yo, conventional-length therapy was ass'd with sig. higher cure rates (88% vs. 77%); in analyses by antibiotic used, diff. was seen for amoxicillin but not Trimethoprim-Sulfamethoxazole therapy (J. Peds. 139:93, 2001--JW)
    2. Tx duration usually 7-10d, though some have suggested shorter courses
    3. For pts < 5yo and all boys, 10-14d is common
  4. Choice of antibiotic
    1. If pt recently on prophylactic abx, select a different antibiotics to tx acute UTI
    2. Per AAP 4/99 tx options include sulfonamides or cephalosporins; many E. coli strains may be resistant to amox
  5. If expected clinical response doesn't occur within 2d of antimicrobial therapy, re-evaluate including repeat urine culture and renal ultrasound to look for evidence of obstruction
  6. If sensitivity testing isn't performed or if bug is found to be intermediate in sensitivity or resitant to the abx used, obtain urine for test-of-cure after 48h of tx
  7. AAP 4/99 recommends continuing abx in "therapeutic or prophylactic dosage" until imaging studies are completed

VII. Surgical tx for anatomic abnormalities thought to predispose to UTI

  1. Most studies on surgery for VUR have used elimination of radiologic signs of reflux as their outcome measures; some controlled trials as of 1996 had found surgical tx of VUR to be as effective as abx prophylaxis at reducing renal scarring
  2. Similarly, clinical impact of surgical tx of urinary tract obstruction is unknown as of 1996

VIII. Antibiotic prophylaxis for secondary prevention of UTI

  1. Appropriate for:
    1. > 2 UTI's in 1y
    2. < 5yo with history of UTI, and grade I-II VUR or other significant structural abnormalities, including renal scarring seen on imaging tests
  2. Some evidence for efficacy at reducing UTI recurrences in up to 2y after index UTI; however, data on impact on incidence of renal scarring, hypertension, and renal failure is limited
    1. In a study in 236 children 3mo-18yo with acute pyelonephritis s/p 14d of acute treatment with antibiotics randomized to antibiotic prophylaxis (daily trimethoprim-sulfamethoxazole or nitrofurantoin) vs. no prophylaxis x 1y, the incidence of recurrent UTI and renal scarring were not sig. diff. in pts with or without VUR. Also, there was no sig. diff. in recurrence or renal scarring based on receipt or non-receipt of antibiotic prophylaxis, regardless of reflux status. (Peds. 117:626, 2006--JW)
    2. In a study in a cohort of 75,000 children < 6yo, use of prophylactive antibiotic therapy after initial UTI was not associated with incidence of recurrent UTI (JAMA 298:179, 2007--JW)  
    3. In a study in 576 children (median age, 14mos) with h/o at least one symptomatic UTI randomized to trimethoprim-sulfamethoxazole QD vs. placebo, over 12mo f/u, incidence of recurrent UTI was sig. lower in the active-treatment group (13% vs. 19%) though the study was not adequately powered to assess effect on kidney function ("Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts ("PRIVENT") Trial; NEJM 361:1748, 2009-FP News; AFP)
  3. Specific regimens--single nightly dose of the following; optimal duration unclear but used x 1-2y or more in clinical studies
    1. Nitrofurantoin 1-2mg/kg
    2. Trimethoprim-sulfamethoxazole, 2mg/kg TMP component
  4. If break through with UTI on prophylaxis, consider the possibility of:
    1. Resistant bugs
    2. Noncompliance
    3. VUR
    4. Voiding dysfunction
  5. Other prophylactice measures:
    1. Wiping back-to-front after defecation (in females)
    2. Avoid constipation
    3. Avoid bubble baths and other topical irritants to urethra in females

IX. Special situations

  1. Asymptomatic bacteriuria--Unclear if abx are indicated (may not decrease risk of renal scarring or incidence of symptomatic UTI)
  2. Recurrent UTI = > 1 UTI in 6mos
    1. Consider possibility of inadequately-tx'd site of persistent infection, e.g. infected calculus
    2. Consider possibility of voiding dysfunction (see above)
    3. Consider prophylactic abx (see above)

Sources: AFP 4/1/98, J. Peds. 128:15, 1996 (the latter a systematic review of 63 studies), AAP guidelines (Pediatrics 103:810-810, 1999), and others as cited.