Urinary Tract Infections in Children

Definition and Classification

Definition

A urinary tract infection (UTI) is an infection (most commonly bacterial, but, rarely, also viral and fungal) of any part of the urinary system, including the urethra, bladder, ureters, or kidneys.

Classification

• Pyelonephritis (upper UTI): infection involving the ureters and kidneys 
• Cystitis (lower UTI): infection of the urinary bladder without renal involvement
• Asymptomatic bacteriuria: positive urine culture without symptoms

Epidemiology and Risk Factors

Epidemiology

Prevalence of UTI: 

• Age dependent: Infants (boys < 1; girls < 4) have a higher prevalence of UTI than older children.
• Gender dependent: Male:female ratio is 1:2 in the 1st year, increases to 1:10 beyond 1–2 years.
• Anatomy dependent: Prevalence is 8 times lower in circumcised boys than in uncircumcised boys.
• Ethnicity dependent: White children have a higher prevalence than Black children.

Risk factors

• Acquired:
  • Recent antibiotic therapy
  • Sexual activity 
  • Bowel dysfunction (pediatric constipation)
  • Indwelling catheter
  • Immunosuppression
• Innate:
  • Urinary tract structural anomalies leading to obstruction 
  • Dysfunctional voiding (neurogenic bladder)
  • Genetics (children with 1st-degree relatives with a history of pediatric UTI are more likely to have UTI)

Etiology and Pathophysiology

Etiology

• Bacterial:
  • Escherichia coli (75%–90%)
  • Klebsiella
  • Proteus 
  • Enterococcus faecalis 
  • Staphylococcus saprophyticus
  • Group B streptococcus (neonates)
  • Pseudomonas
• Fungal (especially with instrumentation):
  • Candida spp
  • Asperigillus spp
  • Cryptococcus neoformans
• Viral: adenovirus and other viruses (seen in cystitis with gross hematuria)

Pathophysiology

Normal urinary tract anatomy and/or urinary dynamics:

• Ascending infection
  • Uropathogens (most commonly fecal flora) colonize periurethral area → ascend to bladder via urethra 
  • If pathogen reaches kidney via ureter → pyelonephritis or upper UTI 
  • Infection may occasionally enter blood → septicemia
• Hematogenous infection
  • Septicemia → UTI
  • Rarely seen, usually in immunocompromised patients

Abnormal urinary tract anatomy and/or urinary dynamics:

• Stagnation of urine leads to pathogen growth and UTIs
  • Anatomical abnormalities leading to obstruction (ureteropelvic junction obstruction, posterior urethral valves)
  • Neurological abnormalities leading to delay in emptying
• Vesicoureteral reflux (VUR): retrograde flow of urine from the bladder along the ureters
  • Common and important cause of febrile UTI leading to pyelonephritis in children
  • Has multiple etiologies
  • Leads to renal scarring if not treated

Clinical Presentation

Infants and young children

• Non-specific symptoms: 
  • Fever (may be the sole symptom, especially fever > 39℃ (101.2°F))
  • Irritability
  • Poor feeding
  • Jaundice
  • Weight loss
• Changes in urinary habits: 
  • Holding urine due to painful urination
  • New incontinence

Older (school-age and up) children

Presentation is similar to adults and clinical symptoms can be used to distinguish upper from lower UTI.

• Pyelonephritis: 
  • Fever 
  • Pain (abdominal, back, or flank)
  • Malaise
  • Nausea and vomiting
  • Diarrhea (occasionally)
• Cystitis:
  • Dysuria
  • Urgency
  • Frequency
  • Suprapubic pain and tenderness
  • Incontinence
  • Malodorous urine
  • Hematuria (caused by E. coli or adenovirus)

Workup and Diagnosis

Clinical suspicion based on age-appropriate symptomatology or urinalysis findings must be confirmed by urine culture.

Obtaining a urine sample

• Who to obtain a sample from:
  • Children 0–2 months: all febrile infants
  • Children 2–24 months: Decision is case dependent, based on height of fever and risk factors.
  • Older children: only if symptoms are suggestive of UTI
• How to obtain a sample:
  • Obtaining sterile urine is key to valid urinalysis results, but challenging with young children.
  • Toilet-trained children: Attempt clean catch (take care to avoid  contamination with skin flora). 
  • Children 2–24 months without toilet training: 
    • Place a bag over genital area (bag sample).
    • Catheterization or suprapubic aspiration may be necessary.

Urinalysis features

• Urinalysis results may suggest UTI but are not diagnostic alone.
• Negative results in the presence of symptoms do not rule out UTI.
• Nitrites and leukocyte esterase usually positive with UTI 
• Pyuria (leukocytes in urine): 
  • May be absent in UTI
  • Sterile pyuria (positive leukocytes and negative culture) may be caused by:
    • Prior antibiotic therapy
    • Viral infections, tuberculosis, renal abscess
    • Urinary tract obstruction
    • Inflammation outside the urinary tract 
    • Interstitial nephritis
• Hematuria (increased RBCs) may be seen.

Urine culture

• Urinalyses suggestive of UTI must be confirmed by urine culture.
• Isolation of a single pathogen with one of the following criteria is diagnostic of UTI:
  • Colony count > 10,000 in a symptomatic child
  • Colony count > 50,000 from a suprapubic/catheter-obtained specimen 
  • Colony count > 100,000 from a urine bag
• Isolation of Lactobacillus spp., coagulase-negative staphylococci, and Corynebacterium spp. are not suggestive of UTI as these are normal skin flora.

Blood culture

When to perform:

• Very young children (< 2 months) who are at high risk for sepsis
• In suspected pyelonephritis before antibiotic therapy

Imaging

Urinary tract infections in children may be indicative of underlying renal anatomical abnormalities, so some must be further investigated with imaging.

• Renal and bladder ultrasound (RBUS) should be performed: 
  • After 1st febrile UTI in all children 2–24 months
  • In all children with recurrent cases of UTI
  • After acute phase of illness; immediately with severe illness 
• Voiding cystourethrogram (VCUG): Dye visible on X-ray is injected into the bladder and urine flow is visualized during voiding.
  • Goal is to confirm presence of vesicoureteral reflux (VUR). 
  • Performed if: 
    • Ultrasound findings suggestive of high-grade (III and above) VUR (majority of grade I or II VURs resolve spontaneously)
    • Evidence of obstruction, such as hydronephrosis or scarring
    • Recurrent febrile UTI
• Late dimercaptosuccinic acid (DMSA) scan: no longer recommended by the American Academy of Pediatrics

Management and Follow-up

Management

The main goal of treatment is prevention of renal complications, such as renal scarring, hypertension, and chronic kidney disease.

• Empiric antibiotic therapy:
  • Early initiation (within 72 hours) prevents renal scarring.
  • Should only be started after urine samples for testing have been collected
  • Should only be started for patients with high likelihood of UTI:
    • Fever > 39℃ (101.2)
    • Known immune deficiency or renal anomaly
    • Septic appearance
• Antibiotic choice:
  • Should be tailored to bacterial species and sensitivity whenever possible
  • Aimed at treating the most likely causative pathogen (E. coli)
    • High kidney involvement risk → 2nd- or 3rd-generation cephalosporin
    • Low kidney involvement risk → 1st-generation cephalosporin

Pyelonephritis

• Admit to hospital if:
  • Septic
  • Dehydrated
  • Nauseous & vomiting
  • < 1 month with suspected UTI
  • < 2 months with febrile UTI
  • Complicated infection (stones, obstruction, anomalies)
• 7–14 days of broad-spectrum antibiotics:
  • Outpatient: oral 3rd-generation cephalosporins (cefixime)
  • Inpatient: IV ceftriaxone, cefotaxime, or ampicillin with an aminoglycoside (gentamicin)
• Fluoroquinolones are effective antibiotics, but are best avoided in patients < 17 years of age.
• Urine culture: 1 week after completion of antibiotics to confirm treatment
• Renal abscess, perirenal abscess, or urinary tract obstruction: surgical or percutaneous drainage + antibiotics

Follow-up

• Children with history of only one uncomplicated UTI do not need follow-up.
• Nephrologist follow-up is recommended for children with:
  • Recurrent UTI
  • Severe VUR (grade III to V)
  • Anatomical renal abnormalities
  • Neurological disfunction of the bladder
  • High blood pressure
• Antibiotic prophylaxis
  • Controversial
  • Still recommended for children with VUR grade III to V