Paediatric Urinary Tract Infection

The urinary tract is a common site of infection in the pediatric population. UTI in the pediatric population is well recognized as a cause of:

• Acute morbidity and chronic medical conditions, such as hypertension.
• Renal insufficiency in adulthood.

Definitions

Definitions related to urinary tract infections (UTI):

• UTI: Defined as colonization of a pathogen occurring anywhere along the urinary tract, which includes the kidney, ureter, bladder, and urethra.
• Bacteriuria: The presence of bacteria in bladder urine, which can be symptomatic or asymptomatic.

Urinary tract infections (UTIs) can be classified based on the following factors:

• Site of Infection: UTIs can occur in different parts of the urinary tract, including:
  • Pyelonephritis (in the kidney)
  • Cystitis (in the bladder)
  • Urethritis (in the urethra)
• Severity: UTIs can be categorized as:
  • Uncomplicated UTIs
  • Complicated UTIs (UTIs with structural or functional abnormalities or the presence of foreign objects, such as an indwelling urethral catheter).

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The epidemiology of pediatric urinary tract infections (UTIs) is characterized by several factors:

• Challenges in Determining Incidence: The true incidence of pediatric UTIs is difficult to determine due to varying presentations, ranging from the absence of specific urinary complaints to fulminant urosepsis.
• Incidence in the USA: In the United States, UTIs affect approximately 2.4% to 2.8% of children every year, leading to more than 1.1 million office visits annually.
• Variation by Age and Gender: The epidemiology of pediatric UTIs varies based on age and gender:
  • During the first year of life, boys have a higher incidence of UTIs.
  • In all other age groups, girls are more prone to developing UTIs.

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Uropathogens, the microorganisms responsible for urinary tract infections, exhibit the following characteristics:

• Less Common Pathogens: In addition to bacteria, urinary tract infections can be caused by less common agents such as fungi, parasites, and viruses.
• Bacterial Origin: The majority of causative agents are bacteria of enteric (intestinal) origin.
• Variation by Age and Comorbidities: The causative agent can vary based on the patient's age and associated comorbidities.
• E. coli Prevalence: E. coli is the most frequently documented uropathogen in urinary tract infections.
• Candida in Certain Cases: In immunocompromised children and those with indwelling catheters, Candida may be isolated from the urine.
• Nosocomial Infections: Nosocomial (hospital-acquired) infections are typically more difficult to treat and can be caused by various organisms, including E. coli, Candida, Enterococcus, Enterobacter, and Pseudomonas.

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The pathogenesis of urinary tract infections (UTIs) involves several mechanisms:

• Fecal-Perineal-Urethral Route: Bacterial clonal studies strongly support entry into the urinary tract by the fecal-perineal-urethral route with subsequent retrograde ascent into the bladder.
• Ascension to the Kidneys: Once the uropathogen reaches the bladder, it may ascend to the ureters and then to the kidneys by some as-yet undefined mechanism.
• Additional Pathways: Other pathways of infection include nosocomial infection through instrumentation, hematogenous seeding in the setting of systemic infection or a compromised immune system, and direct extension caused by the presence of fistulae from the bowel or vagina.
• Risk Factors for Girls: Girls are at a higher risk of UTI than boys beyond the first year of life due to differences in anatomy. The moist periurethral and vaginal areas promote the growth of uropathogens, and the shorter urethral length increases the chance for ascending infection into the urinary tract.
• Urinary Tract Characteristics: The urinary tract, including the kidney, ureter, bladder, and urethra, is a closed, normally sterile space lined with mucosa composed of epithelium known as transitional cells.
• Defense Mechanisms: The main defense mechanism against UTIs is constant antegrade flow of urine from the kidneys to the bladder with intermittent complete emptying of the bladder via the urethra. This washout effect of urinary flow usually clears the urinary tract of pathogens.
• Antimicrobial Characteristics: Urine itself has specific antimicrobial characteristics, including low urine pH, polymorphonuclear cells, and Tamm-Horsfall glycoprotein, which inhibits bacterial adherence to the bladder mucosal wall.
• UTI Development: UTI occurs when pathogens are introduced into this space and adhere to the mucosa of the urinary tract. Inadequate clearance of uropathogens by the washout effect may lead to microbial colonization, multiplication, and an associated inflammatory response.
• Virulence Factors: Bacteria that cause UTI often possess virulence factors to overcome the normal defenses of the urinary system. These factors include enhanced adherence to uroepithelium by adhesins, toxins that cause cellular lysis, and mechanisms to acquire essential nutrients like iron.
• Defensive Mechanisms: Uropathogenic strains of E. coli have defensive mechanisms such as a glycosylated polysaccharide capsule that interferes with phagocytosis and complement-mediated destruction.
• O & H Antigens: Some bacteria express specific O & H antigens on their surfaces, with K-antigen conferring resistance to bactericidal effects of serum and enhancing bacterial survival in tissues, while O-antigen is toxic and induces acute inflammation.

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While all individuals are susceptible to urinary tract infections (UTIs), most remain infection-free during childhood due to innate resistance to uropathogen attachment. However, specific subpopulations have an increased susceptibility to UTIs. These risk factors include:

• Inadequate Antibiotic Treatment: Upper UTIs that are treated with an insufficiently short course of antibiotics.
• Stones: Presence of stones in the urinary tract.
• Abscess: Formation of abscesses in the urinary tract.
• Gross Urological Abnormality: The presence of significant urological abnormalities.
• Constipation: Chronic constipation, which can contribute to UTI risk.
• Neuropathic Bladder: Conditions leading to a neuropathic bladder.
• Anatomical Factors: Various anatomical factors can increase susceptibility to UTIs, including:
  • Bladder diverticulum.
  • Calculi (stones) in the urinary tract.
  • Shortened urethra in girls, which increases the risk of infection.
• Immunological and Cellular Factors: Certain immunological and cellular factors can increase UTI risk, including:
  • Immature immune systems in infants.
  • Low levels of secretory IgA in body fluids.
  • P1 blood group.
  • B blood group.

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The definitive diagnosis of a urinary tract infection (UTI) requires the isolation of at least one uropathogen from a urine culture. Urine should be collected before initiating antimicrobial therapy and can be obtained by various methods:

• Bagged Specimen: The simplest and least traumatic method involves attaching a plastic bag to the perineum. While useful for ruling out a UTI, it has limited accuracy for documenting one.
• Clean-Catch Midstream Urine Specimen: Older children can provide this type of specimen, but it is often contaminated with periurethral and preputial organisms, making culture interpretation challenging.
• Urethral Catheterization: This is commonly used in young children and is reliable if the initial portion of urine, potentially contaminated by periurethral organisms, is discarded. However, it is invasive.
• Suprapubic Aspiration: Considered the gold standard for identifying bacteria within the bladder. The AAP recommends this method in neonates and young children for UTI diagnosis.

The reference standard for UTI diagnosis is the isolation of a single uropathogen from a specimen obtained at specific concentrations (Kass criteria):

• >10³ or 1,000 colony-forming units (CFU)/mL for a specimen from suprapubic aspiration (SPA).
• >10⁴ or 10,000 CFU/mL for a catheter specimen.
• >10⁵ or 10,000 CFU/mL for a 'clean-catch,' midstream specimen.

• Dipstick Urinalysis:
  • Leucocyte esterase
  • Nitrite test (indicating bacteriuria)
  • Proteinuria
• E/U (electrolytes/urea) and Cr (creatinine) in the sick child
• If the clinical picture and urinalysis are equivocal, additional tests such as a complete blood count, erythrocyte sedimentation rate, and C-reactive protein may help determine the presence of a UTI and the need for presumptive treatment.

Urine Dipstix

• Blood/Protein: These parameters are non-specific and can result from many other causes.
• Leukocyte Esterase Test:
  • Sensitive for leukocytes but not specific for UTIs, especially in girls.
• Nitrite Test for Bacteria:
  • High specificity (99%) but low sensitivity (50%).
• pH: Alkaline urine may indicate a Proteus infection.
• Urine with any positive parameters should be sent for culture.
• Negative parameters are accepted as negative.

Sterile Pyuria: Common Causes

Sterile pyuria is characterized by the presence of white blood cells (WBCs) in the urine without the concurrent presence of bacteria. It is defined as the identification of more than 10 white blood cells per high-power field (hpf) upon microscopic examination of a freshly voided urine specimen, while urine culture results are negative for bacterial growth. Common causes include

• Fever: Often associated with systemic or viral infections.
• Acute systemic/virus infections: Such as those causing flu-like symptoms.
• Dehydration: Can lead to concentrated urine and pyuria.
• Vulvovaginitis & urine reflux in vagina: In females, this can sometimes mimic urinary tract issues.
• Balanitis: An inflammation of the head of the penis, which may result in sterile pyuria in males.
• Glomerulonephritis, interstitial nephritis: Kidney conditions that can present with pyuria.
• Half-treated UTIs (Antibiotic): Incomplete treatment of a previous urinary tract infection.
• Appendicitis: An inflamed appendix may lead to sterile pyuria.
• Tuberculosis (Relatively uncommon in children): TB can affect the urinary tract in rare cases.
• Kidney stones (Usually infective in children): Stones may cause infections.
• Cystic diseases of the kidneys: Conditions that affect kidney structure.

Renal Imaging

• Detection of anatomic and functional urinary tract abnormalities
• Ultrasonography (USS) - comparing values to age-related ranges
• Micturating cystourethrogram (MCUG)
• +/- Intravenous urography (IVU)
• Scintigraphy using 99TC DMSA scanning (affected areas are seen as uptake defects, making it sometimes difficult to determine if lesions are longstanding).

Specific Indications for Diagnostic Imaging in Patients at Risk of Scarring

• Acute pyelonephritis
• Bacteriuria in infancy
• Hypertension
• Presence of an abdominal mass
• Posterior midline anomalies
• Decreased renal concentrating ability
• Recurrent cystitis in males

Management Objectives for Sterile Pyuria

• To alleviate symptoms: Focus on relieving discomfort and addressing underlying causes.
• To prevent/minimize renal damage: Aim to protect the kidneys from any potential harm.
• Identify structural abnormalities that require surgery: Assess for any anatomical issues that may need surgical intervention.

Principles:

• Children with symptomatic UTI should commence treatment immediately once samples have been collected.
• The choice of antibiotics should be based on local epidemiologic data.
• Oral antibiotics are effective in most cases.
• Parenteral antibiotics are indicated when there is persistent vomiting or when the child has associated sepsis.
• Treatment duration depends on the nature of the organism and the presence or absence of structural anomalies.

Short-term Complications

• Dissemination of infection
• Pyonephrosis

Long-term Consequences

• UTI causes significant morbidity in children, inconveniences, and anxiety for the family, as well as considerable consumption of medical resources.
• It occurs in 10–15% of cases and is particularly common with repeated infections and in individuals with congenital malformations.
• Unilateral lesions are more common.
• Bilateral involvement can progress ultimately to CKD (Chronic Kidney Disease).
• Other effects include an increased incidence of hypertension in later life and increased morbidity during pregnancies.
• Predisposition to nephrolithiasis and nephrocalcinosis.
• Reflux nephropathy
• Failure to thrive

• Careful perineal hygiene
• Prevent constipation/bladder training (complete bladder emptying)
• Low-dose prophylaxis with:
• VUR (Vesicoureteral Reflux)
• Recurrent UTI (Urinary Tract Infection)
• Neurogenic bladder

^aDose adjustment required for azotemia

Infections of the urinary tract are among the most common infections in the pediatric population. If not treated promptly and appropriately, pediatric UTI may lead to significant acute morbidity and irreversible renal damage. Children have a wide variety of clinical presentations, ranging from the asymptomatic presence of bacteria in the urine to potentially life-threatening kidney infections.

A clinician's main goals are early diagnosis, appropriate antimicrobial therapy, identification of anatomic anomalies, and preservation of renal function. Treatment should be based on urine culture. Children noted to have renal scarring after an acute episode of UTI should be followed long-term for signs of hypertension and renal insufficiency.