Kathleen Kieran, MD, FAAP, FACS
Christopher S. Cooper, MD, FAAP, FACS
BASICS
DESCRIPTION
• A urinary tract infection (UTI) represents inflammatory changes in the urinary tract caused by the presence of an infectious agent
• Spectrum of severity, from local infection to systemic changes/urosepsis
EPIDEMIOLOGY
Incidence
• 180,000 children annually will develop UTI in the United States
• 0.7% of all pediatric office visits each year (3.5–5% of emergency department visits)
• Overall 2% of febrile infants, 5% of all infants:
– 21% of uncircumcised male infants
– 5% of female infants
– 2.3% of circumcised male infants
Prevalence
Prevalence is variable and closer to an adult level as age groups increase
RISK FACTORS
• Previous UTI:
– ∼25% of infants with a symptomatic UTI will have a recurrence
– Older females may have a 40–60% risk of recurrent infection
• Immunosuppressive states, including diabetes, chemotherapy, and steroid use
• Anatomic and functional abnormalities of the urinary tract which predispose to urinary stasis:
– Vesicoureteral reflux, ureterocele, ureteropelvic junction obstruction, bladder diverticula, posterior urethral valves
– Neurogenic bladder, dysfunctional voiding/elimination behaviors (eg, constipation)
• Urologic instrumentation (catheters)
• Older children: Sexual activity
• Circumcision (1):
– Uncircumcised males <1 yr of age have the highest rate of UTI of all gender and age groups (10 times higher than circumcised males)
– AAP has stopped short of endorsing routine circumcision, but acknowledges apparent protective effect against UTIs and penile cancer
– Consider circumcision in infant males with UTI
Genetics
• Incompletely understood
• Multifactorial, including altered carbohydrate secretion antigens on cell surface molecules which may increase bacterial adherence
PATHOPHYSIOLOGY
• Usually ascending infections, although hematogenous spread can be seen in infants or immunocompromised populations
• Colonization of female introitus or male preputial epithelium with intestinal flora
• The most common pathogen is Escherichia coli (∼85%)
• Other uropathogens include Klebsiella, Proteus, Enterobacter, Citrobacter, Staphylococcus saprophyticus, and Enterococcus
• Viral (eg, adenovirus, BK virus) and fungal (Candida) infections may be seen in immunocompromised patients
• Both humoral and cellular responses result in inflammation of the urinary tract
• Bacterial virulence factors include O antigen (part of lipopolysaccharide), K antigen (part of capsule), and P fimbriae contributes to bacterial ascent to the upper tracts, even in the absence of reflux
ASSOCIATED CONDITIONS
• Dysfunctional elimination including incontinence, holding or retention of urine, and constipation increase risk of UTI
• Immunocompromise
• Structural abnormalities of the GU tract
GENERAL PREVENTION
• Good voiding/elimination habits
• Treatment of constipation
• Identification and treatment of underlying urologic conditions which may predispose to urinary stasis
DIAGNOSIS
HISTORY
• Vague in infants:
– Symptoms: Fever, irritability, poor feeding, vomiting, diarrhea, abdominal distention, foul-smelling urine
– Older children may complain of dysuria, incontinence, changes in voiding habits, flank or abdominal pain, enuresis
• Presence, severity, and duration of fever
• Previous UTIs and how documented (eg, culture, urinalysis, symptoms)
• Prenatal history including prenatal ultrasounds
• Previous GU/GI surgery
• Family history of infections and/or GU anomalies
PHYSICAL EXAM
• Specific findings in infants are rare; may see fever, failure to thrive, jaundice, or lethargy
• Older children may have suprapubic, flank, abdominal and/or upper quadrant tenderness
• CVA tenderness suggests pyelonephritis
• A scrotal exam will help rule out epididymitis
• Careful external genital exam to rule out trauma, local irritation, urethral discharge, phimosis, and anatomic abnormalities
• Circumcision status
• Palpable abdominal or flank mass (eg, severe hydronephrosis or distended bladder)
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urine analysis (2):
– Microscopic exam after dipstick urine analysis increases the test’s sensitivity and specificity. It can also yield clues to contamination (epithelial cells)
– Positive leukocyte esterase (indicates WBCs in the urine) is up to 95% sensitive in children with symptoms
– Positive nitrite (many gram-negative bacteria produce this substance) has a sensitivity of 30–45%, but a specificity that nears 100%
– Combined positive nitrite-leukocyte esterase 80–90% sensitive and 60–98% specific
– >10 WBCs per HPF on an unspun specimen or >5 WBCs on a spun sediment is usually indicative of infection
– Identification of bacteria on Gram stain has a sensitivity and specificity better than that of a dipstick evaluation for nitrite and leukocyte esterase
• Urine culture is the gold standard to diagnose UTI (2):
– >100,000 CFU/mL on a voided or catheterized specimen, and any bacteria on a suprapubic aspirate is generally considered a positive culture
– Lower colony counts in symptomatic children, or growth of pathogenic bacteria (eg, Klebsiella, Pseudomonas) should also be treated
– In non-toilet trained children, >50,000 CFU/mL of a single pathogen is also consistent with UTI
• Blood tests are unreliable in diagnosing UTI
• Asymptomatic bacteriuria (no symptoms, <5 WBC/hpf, but positive culture) should prompt treatment if a pathogenic organism is present
Imaging
• The need for and timing of imaging following UTI remains controversial; it is not required in the acute setting, but may be indicated at follow-up
– Consider evaluating all children <5 yr after their 1st documented UTI; and all girls, regardless of age, with febrile or recurrent infections, particularly with voiding dysfunction
– Renal/bladder US should be considered following a febrile UTI
– Need for and timing of VCUG is controversial: The American Academy of Pediatrics (AAP) recommends VCUG after second febrile UTI unless there is a suspicion of underlying anatomic abnormality (3), while most pediatric urologists recommend VCUG following first febrile UTI
• 40% of children with a single febrile UTI have VUR
• Absence of clinical improvement after 48 h of appropriate treatment should raise concern for structural or functional abnormalities
• DMSA scan may reveal renal inflammation in acute pyelonephritis and/or scarring from previous infections
• Older girls with recurrent cystitis in the absence of voiding dysfunction should be evaluated with pre- and post-void renal and bladder sonography (4)
• In toilet-trained children in whom voiding dysfunction may be a factor, assessment of voiding patterns (eg, uroflow) may be helpful
Diagnostic Procedures/Surgery
None specific, though cystoscopy may be performed for associated conditions or chronic infections as indicated
Pathologic Findings
• Cystitis and pyelonephritis are generally associated with inflammatory response
• Renal scarring may be manifested by architectural changes including collagen deposition and glomerular loss
DIFFERENTIAL DIAGNOSIS
• UTIs present similarly to other infections:
– Bacteremia and sepsis
– Epididymitis
– Gastroenteritis
– Sexual abuse
– STD/STI in a sexually active child
– Vaginitis
• Also consider: Appendicitis, diabetes, dysfunctional voiding/elimination, pregnancy in postpubertal females, urolithiasis, urinary obstruction
ALERT
Findings suggestive of an STI/STD infection should raise concern for sexual abuse
TREATMENT
GENERAL MEASURES
• Initial, empiric treatment should be based on clinical suspicion of UTI as well as reliability of patient and family
• As the symptoms are often vague, a high index of suspicion must be maintained to ensure early detection of pyelonephritis
• Hospitalization might be required based on patient age and clinical status, although infants >2 mo and nontoxic children with suspected pyelonephritis can be treated as outpatients as long as compliance is not an issue
• Children with asymptomatic bacteriuria may not require treatment with antibiotics if the urinary system is otherwise normal
MEDICATION
ALERT
• In children, use 7–14 day treatment course (<7 days has been shown to be inferior).
• Fluoroquinolones should not be a 1st-line choice and are limited to resistant organisms.
• Nitrofurantoin has poor tissue penetration and should not be used for suspected pyelonephritis.
• Age of child and comorbid conditions should be considered when selecting antibiotics.
First Line
• Infants <2 mo (IV therapy preferred)
– Ampicillin Neonates <7 d. 50–100 mg/kg/24 h IV ÷ q8h Term infants.75–150 mg/kg/24 h ÷ q6–8h IV Children >1 mo. 200 mg/kg/24 h ÷ q6h IM or IV
– Gentamicin Infants <7 d <1200 g. 2.5 mg/kg/dose q18–24h.Infants >1200 g: 2.5 mg/kg/dose q12–18h. Infants >7 d: 2.5 mg/kg/dose IV q8–12h. Children: 2.5 mg/kg/d IV q8h; ↓ w/ renal Insufficiency
– 3rd-generation cephalosporin
• Cefixime: 8 mg/ kg/d PO ÷ daily-bid; ↓ w/ renal impairment
• Cefdinir: 7 mg/kg PO bid or 14 mg/kg/d PO; ↓ in renal impairment
• Ceftibuten: 9 mg/kg/d PO; ↓ in renal impairment; take on empty stomach (susp)
• Children >2 mo
3rd-generation cephalosporin: Cefixime, Cefdinir, Ceftibuten
• Children <2 yr of age should be treated with therapeutic doses (IM, IV, PO, or combination)
• School-aged children without systemic signs may be treated with an oral broad-spectrum antibiotic such as SMZ-TMP, nitrofurantoin
• Appropriate to start broad-spectrum antibiotics while awaiting culture results (5)
Second Line
Antibiotic course should be tailored by comorbidities, age, and local bacterial resistance patterns
SURGERY/OTHER PROCEDURES
• May be indicated following resolution of infection if child has specific urinary abnormalities predisposing to or exacerbating effects of urinary tract infection (eg, obstruction, VUR)
• Surgical correction of reflux is aimed at protecting upper tracts and is associated with a decrease in the number of febrile UTIs
ADDITIONAL TREATMENT
• In children with UTI and dysfunctional voiding/elimination behaviors, improvement in the latter will often result in fewer recurrent UTIs
• Regular (eg every 2 h) voiding
• Avoidance of constipation
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
• Cranberries may be effective in decreasing bacterial adherence, but there are no specific recommendations for children at present
• Probiotics may favorably alter gastrointestinal flora, but again there are no specific recommendations for use
ONGOING CARE
PROGNOSIS
• Most children do not have any long-term sequelae from a single UTI
• Prompt, efficacious treatment can prevent systemic sequelae
• Recurrence is common, especially in those with anatomic/functional abnormalities
• Identification of predisposing and comorbid factors may help prevent recurrent UTI
COMPLICATIONS
• Renal insufficiency/failure: Renal scarring in ∼8% of children overall
• Urosepsis
FOLLOW-UP
Patient Monitoring
• If scarring is present, consider a nephrology consult to monitor for evaluation of HTN, proteinuria, and renal insufficiency
• Patients with a history of UTI may be more likely to develop UTIs and toxemia during pregnancy (CITE)
Patient Resources
National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov
REFERENCES
1. American Academy of Pediatrics Task Force on Circumcision. Male circumcision. Pediatrics. 2012;130:e756.
2. Shaikh N, Morone NE, Lopez J, et al. Does this child have a urinary tract infection? JAMA. 2007;298:2895.
3. Newman TB. The new American Academy of Pediatrics urinary tract infection guideline. Pediatrics. 2011;128:572.
4. Bauer R, Kogan B. New developments in the diagnosis and management of pediatric UTIs. Urol Clin N Am. 2008;35:47–58.
5. Sedberry-Ross S, Pohl H. Urinary tract infections in children. Curr Urol Rep. 2008;9:165.
ADDITIONAL READING
Urinary Tract Infection: Clinical Practice Guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128:595–610.
See Also (Topic, Algorithm, Media)
• Urinary Tract Infection (UTI), Complicated, Pediatric
• Urinary Tract Infection, Pediatric Algorithm 
• Vesicoureteral Reflux, Pediatric
CODES
ICD9
• 041.49 Other and unspecified Escherichia coli [E. coli]
• 599.0 Urinary tract infection, site not specified
• 771.82 Urinary tract infection of newborn
ICD10
• B96.20 Unsp Escherichia coli as the cause of diseases classd elswhr
• N39.0 Urinary tract infection, site not specified
• P39.3 Neonatal urinary tract infection
CLINICAL/SURGICAL PEARLS
• A high index of suspicion is often required for an accurate diagnosis of UTI, especially in nonverbal children.
• Treatment of the acute infection should be tailored to the child’s age, comorbidities, and clinical condition, as well as local antibiotic resistance patterns and culture results.
• Surgical intervention is undertaken when conservative management is unlikely to prevent further UTIs and/or protect the kidneys.
• Patients with recurrent febrile infections, VUR, and/or kidney scarring should be followed carefully for development of renal disease.