II. Epidemiology

  1. UTI Incidence
    1. Newborns
      1. Overall: 0.14%
      2. Febrile newborns: 7%
        1. Most common serious Bacterial Infection in children <3 months old
    2. Symptomatic UTI under age 6 years
      1. Girls: 7%
      2. Boys: 2%
      3. Recurrence rate: 30%
    3. School aged children: 1-2%
    4. Ages 7 to 11 year old females: 2.5%
  2. Vesicoureteral Reflux (VUR) Incidence
    1. School aged children with UTI: 25-40%
    2. Preschool sibling of child with VUR: 25-33%
    3. Child of parent with VUR: 65%

III. Causes (single organism in most cases)

  1. Bacteria
    1. Escherichia coli (up to 85% of UTIs in children)
    2. Klebsiella
    3. Proteus (boys and associated with Nephrolithiasis)
    4. Enterobacter
    5. Citrobacter
    6. Enterococcus
    7. Pseudomonas
    8. Staphylococcus saprophyticus
    9. Coagulase negative Staphylococcus
  2. Viral
    1. Adenovirus (hemorrhagic cystitis)
  3. Atypical causes
    1. Fungal
    2. Mycobacterium
    3. Schistosomiasis

IV. Risk Factors: Decision to evaluate for UTI

  1. Infants under age 2 months
    1. Age under 2 months is excluded from this guideline
    2. See Neonatal Sepsis guidelines
  2. Infants and children age 2 to 24 months (with fever >38 C)
    1. Urinary Tract Infection is responsible for 7-15% of fever in infants
    2. Risk factors for girls (<2 is reassuring and indicates a risk <1%)
      1. White race
      2. Age under 12 months
      3. Fever 39 C or higher
      4. Fever lasting more than 48 hours
      5. Absence of other source of infection
    3. Risk Factors for circumcised boys (<3 is reassuring and indicates a risk <1%)
      1. Non-black race
      2. Age under 6 months
      3. Fever 39 C or higher
      4. Fever lasting more than 24 hours
      5. Absence of other source of infection
    4. Risk Factor for uncircumcised boys
      1. Uncircumcised boys have a risk >1% even in absence of other risk factors
      2. Male uncircumsized infants have a higher risk of Urinary Tract Infection than girls
    5. References
      1. Newman (2002) Arch Pediatr Adolesc Med 156:44-54 [PubMed]
      2. Gorelick (2000) Arch Pediatr Adolesc Med 154(4): 386-90 [PubMed]
      3. Shaikh (2007) JAMA 298(24): 2895-2904 [PubMed]
  3. Children over age 2 years
    1. Typical Urinary Tract Infection symptoms
    2. Constipation
    3. Encopresis
    4. Bladder instability
    5. Infrequent voiding
    6. Koff (1998) J Urol 160:1019-22 [PubMed]

V. Findings: Signs and Symptoms

  1. Newborn
    1. Jaundice
    2. Sepsis
    3. Failure to Thrive
    4. Vomiting
    5. Fever
  2. Infant or toddler
    1. Failure to Thrive
    2. Fever
    3. Weight Loss
    4. Nausea or Vomiting
    5. Irritability
    6. Jaundice
    7. Strong smelling urine
    8. Hematuria
    9. Abdominal Pain or Flank Pain
  3. Child
    1. Same as for adult Urinary Tract Infection
    2. Dysuria
    3. Urinary Frequency or urgency
    4. Urine hesitancy
    5. Lower Abdominal Pain
    6. New onset Urinary Incontinence
    7. Urine Odor does not predict Urinary Tract Infection

VI. Diagnosis

  1. General
    1. Urinalysis dipstick can be used to rule-out UTI
      1. High Negative Predictive Value if normal
        1. Exception: Not sensitive in dilute urine (SG<1.005)
          1. Shaw (1998) Pediatrics 101:E1 [PubMed]
        2. However, Urinalysis may still have a 6-10% False Negative Rate
      2. Initial criteria for empirically starting UTI treatment
        1. Catheterized specimen AND
        2. Positive for Leukocyte esterase, nitrite or microscopy with Urine WBCs or Bacteria
    2. Urine Culture is required for UTI diagnosis
      1. Urinalysis dipstick testing is not diagnostic (use only for empiric initial therapy)
      2. Urine Culture is mandatory when a Urinary Tract Infection is suspected
        1. Urine sample for culture must be via catheter or SPA in children under 24 months
        2. Diagnosis requires pyuria and a catheterized specimen with >50,000 colonies of a single organism
  2. Urine Sample Techniques
    1. Urine catheter specimen
      1. Recommended if child under age 2 years
      2. Consider Bladder Ultrasound first (one third of infants have a dry catheterization)
        1. Visualize Bladder in transverse plane
        2. Bladder width >2 cm holds sufficient urine for catheterization sample
    2. Suprapubic Aspirate (SPA, rarely done in U.S. practice)
      1. Consider for child under age 6 months old
    3. Clean catch Urine (especially first morning void)
      1. See Noninvasive Urine Collection (includes Quick-Wee Method, Bladder stimulation technique)
      2. Possible in young children, but requires patience
    4. Urine Bag Collection (Not recommended)
      1. High Incidence of contamination
      2. May only be used to rule out UTI when risk of UTI is low (<1%, see above)
      3. If abnormal, catheterized sample or suprapubic aspirate is required
      4. Avoid Urine Culture of a bag specimen (False Positive culture rate >88%)
  3. Urinalysis Individual Factors (Sensitivity, Specificity)
    1. Urine Leukocyte Esterase (small or greater)
      1. Test Sensitivity: 83%
      2. Test Specificity: 78%
      3. Probability of UTI when positive: 30%
    2. Urine Nitrite
      1. Requires 4 hours within the Bladder to form (young children do not hold their urine)
      2. Test Sensitivity: 53%
      3. Test Specificity: 98%
      4. Probability of UTI when positive: 75%
    3. Urine White Blood Cells (10 or greater; some criteria use 5 or greater) on microscopy (hpf)
      1. Test Sensitivity: 73%
      2. Test Specificity: 81%
      3. Probability of UTI when positive: 30%
    4. Urine Bacteria present on microscopy
      1. Test Sensitivity: 81%
      2. Test Specificity: 83%
      3. Probability of UTI when positive: 35%
    5. Urine Red Blood Cells on microscopy
      1. Test Sensitivity: 47%
      2. Test Specificity: 78%
      3. Probability of UTI when positive: 19%
  4. Urinalysis Combined Factors (Sensitivity, Specificity)
    1. Urine Leukocyte Esterase AND Urine Nitrite Combined
      1. Test Sensitivity: 93%
      2. Test Specificity: 72%
    2. Urine Leukocyte Esterase AND Urine Nitrite AND positive microscopy (Bacteria or WBC>5/hpf)
      1. Test Sensitivity: 99.8%
      2. Test Specificity: 70%
      3. Very high Negative Predictive Value
  5. Urine Culture
    1. See Urine Culture for diagnostic criteria
    2. Positive if catheterized specimen with >50,000 colonies of a single organism
    3. Culture sample within 4 hours or refrigerate
    4. Obtain in all children <10 years old when Urinalysis is evaluated (Urinalysis can be unreliable)
  6. Resources
    1. UtiCalc Tool (University of Pittsburgh)
      1. https:..uticalc.pitt.edu
      2. Predicts likelihood of UTI (tool recommends Urinalysis if >2% risk)

VII. Labs

  1. Precautions
    1. Always obtain urine sample before antibiotics are started (antibiotics rapidly render sterile urine)
  2. Standard
    1. Urinalysis
    2. Urine Culture
  3. Suspected Pyelonephritis
    1. Complete Blood Count (CBC)
    2. Blood Culture
      1. Indicated for febrile hospitalized child
      2. UTI with bacteremia may necesitate earlier imaging
    3. Inflammation Markers (70-80 sensitive, not specific)
      1. Erythrocyte Sedimentation Rate
      2. C-Reactive Protein
    4. Renal Function tests)
      1. Blood Urea Nitrogen
      2. Creatinine

VIII. Imaging

  1. General
    1. First UTI in age <5 years old no longer requires imaging (unless indicated as below)
    2. Does not appear to change management or outcome (significant VUR Incidence is low)
    3. Zamir (2004) Arch Dis Child 89:466-8 [PubMed]
  2. Imaging indications
    1. Renal and Bladder Ultrasound
      1. Indications
        1. First UTI with fever at least 101.3 F (38.5 C) age under 2 years
        2. Recurrent UTI ages 2 to 5 years
      2. Timing
        1. Within 48 hours for severe infection or prolonged course
        2. Otherwise wait until acute infection resolves, and obtain within 6 months of acute infection
    2. VCUG
      1. Do not routinely obtain for first febrile UTI
      2. Do not obtain until infection has resolved (wait at least 3-6 weeks after infection)
      3. Indicated for abnormal Ultrasound showing renal scar, Hydronephrosis or other signs of high grade VUR
      4. May also be indicated for second febrile Urinary Tract Infection (discuss with pediatric urology)
    3. DMSA Renal Cortical Scan
      1. Less commonly used now (defer to local pediatric urology consultants)
      2. May be preferred in girls as spares some ovarian radiation seen in VCUG

IX. Management: Overall protocol for a febrile child between ages 2 months and 24 months

  1. Step 1: Child requires immediate empiric antimicrobial therapy
    1. Go to Step 4
  2. Step 2: Likelihood of Urinary Tract Infection is <1% (see Decision to evaluate for UTI as above)
    1. No urine testing required
    2. Complete additional evaluation of a febrile child
    3. Follow-up in 1-2 days for re-evaluation
  3. Step 3: Negative Urinalysis (LE, Nitrite, micro) by any method
    1. No further urine testing required
    2. Complete additional evaluation of a febrile child
    3. Follow-up in 1-2 days for re-evaluation
  4. Step 4: Urine Culture by catheter, clean catch or suprapubic aspirate only
    1. Determine disposition based on inpatient criteria below
    2. Start antibiotics as described below
  5. Step 5: Negative Urine Culture
    1. Stop antibiotics
    2. Complete additional evaluation of a febrile child
    3. Follow-up for Recurrent Fever
  6. Step 6: Positive Urine Culture
    1. Treat for 7-14 days adjusted for Urine Culture sensitivities
  7. Step 7: Renal and Bladder Ultrasound
    1. Obtain at any time after Urinary Tract Infection is confirmed
    2. Positive Ultrasound for anatomic abnormalities (e.g. Hydronephrosis)
      1. Obtain VCUG to evaluate for Grade IV to IV vesicoureteral reflux
  8. References
    1. Roberts (2011) Pediatrics 128(3): 595-610 [PubMed]

X. Management: Inpatient criteria

  1. Ill appearing or toxic children
  2. Children unable to maintain oral hydration
  3. Risk of renal scar
  4. Febrile children under age 6 months to 1 year old

XI. Management: Antibiotics

  1. Precautions
    1. Initiate early empiric antibiotics after urine sample when UTI is suspected in young children
      1. Delaying treatment for Urine Culture results (48 hours) increases renal scarring risk
    2. Oral antibiotics are as effective as intravenous antibiotics for UTI in Children >2 months of age
      1. When IV antibiotics are used, short course (2-4 days) followed by oral antibiotics is effective
      2. Strohmeier (2014) Cochrane Database Syst Rev (7):CD003772 [PubMed]
      3. Desai (2019) Pediatrics 144(3):e20183844 [PubMed]
  2. Oral antibiotics for 7 to 14 days (10 days or more if fever present)
    1. Amoxicillin-clavulonate (Augmentin) 45 mg/kg/day divided twice daily
      1. E coli resistance to Amoxicillin is increasing (>50% in some regions as of 2016)
    2. Trimethoprim Sulfamethoxazole (Septra, Bactrim)
      1. Dosing: 6-12 mg/kg/day TMP,30-60 mg/kg/day SMZ divided bid
      2. Avoid under age 2 months
      3. Poor renal penetration
      4. E coli resistance to TMP-SMZ is also increasing (25% in some regions as of 2016)
    3. Second generation or Third Generation Cephalosporins
      1. Cefixime (Suprax)
        1. Expensive
        2. Day one: 16 mg/kg for the first day
        3. Next: 8 mg/kg/day in single dose or divided every 12 hours
      2. Cefpodoxime (Vantin) 10 mg/kg/day divided every 12 hours
      3. Cefprozil (Cefzil) 30 mg/kg/day divided every 12 hours
      4. Cephalexin (Keflex) 25-50 mg/kg/day orally divided three to four times daily
        1. Good renal parenchymal penetration and Pyelonephritis coverage
  3. Intravenous antibiotics for hospitalized children
    1. Preferred agents
      1. Cefotaxime 50 mg/kg IV every 8 hours
      2. Ceftriaxone (Rocephin) 75-100 mg/kg every 24 hours
      3. Ceftazidime 50 mg/kg every 8 hours
    2. Other antibiotic options
      1. Gentamicin
        1. Neonates <8 days: 4 mg/kg/day divided every 8 hours OR once daily
        2. Neonates 8 to 60 days: 5 mg/kg/day divided every 8 hours OR once daily
        3. Children >60 days: 7.5 mg/kg/day divided every 8 hours OR once daily
      2. Tobramycin 5 mg/kg/day divided every 8 hours
      3. Piperacillin 300 mg/kg/day divided every 6-8 hours

XII. Management: UTI Prophylaxis

  1. Indications
    1. Prophylaxis is no longer routinely recommended prior to completion of evaluation
    2. Discuss with local pediatric urology consultants
  2. Medications (at bedtime if toilet trained)
    1. Nitrofurantoin (Furadantin, Macrodantin, Macrobid)
      1. Dosing: 1-2 mg/kg once daily
      2. Preferred UTI prophylaxis agent
        1. Associated with less Antibiotic Resistance than other prophylaxis agents
      3. Adverse effects
        1. May be associated with greater gastrointestinal side effects (Nausea, Vomiting, Abdominal Pain)
    2. Trimethoprim Sulfamethoxazole (Septra, Bactrim)
      1. Avoid under 2 months
      2. Dosing
        1. Nightly: 2 mg TMP/10 mg SMZ per kg at bedtime
        2. Bi-weekly: 5 mg TMP/25 mg SMZ per kg twice weekly
    3. Nalidixic Acid (NegGram)
      1. Dosing: 30 mg/kg/day divided bid
    4. Methenamine mandelate 75 mg/kg/day divided bid
    5. Sulfisoxazole (Gantrisin) 10-20 mg/kg/day divided bid
  3. Other prevention
    1. Circumcision in uncircumsized boys
    2. Treat comorbid Constipation

XIII. Management: Evaluation for secondary urologic anomaly

  1. Indications
    1. See Imaging above
    2. Family History may dictate screening despite no prior personal UTI history
      1. Preschool siblings of child with urologic anomaly
      2. Preschool child of parent with vesicoureteral reflux
  2. Protocol
    1. See Imaging above

XV. Prognosis: Vesicoureteral Reflux

  1. Risk End-stage renal disease if renal scarring occurs
    1. Responsible for 20% of end-stage renal disease
  2. Spontaneous Resolution Rates for Ureteral Reflux
    1. Grade I: 70-80%
    2. Grade II: 70-80%
    3. Grade III: 50%
    4. Grade IV: 15%
    5. Grade V: <15%

XVI. Prevention: Prevent renal scars in high risk children

  1. Children under age 2 years
  2. Recurrent Pyelonephritis
  3. Pyelonephritis with urinary anatomic abnormality
  4. Pyelonephritis untreated for more than 3 days

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