Christopher J. Long, MD
Douglas A. Canning, MD, FACS
BASICS
DESCRIPTION
• A complicated urinary tract infection (UTI) is an infection in the presence of abnormalities of metabolism, GU structure, or function
• There is an increased risk of therapy failure and patient morbidity and mortality.
• For recurrent UTI:
– Unresolved: Incompletely treated infection
– Reinfection: Infection by another organism
– Persistent infection: Seeding from another site (ie, abscess)
EPIDEMIOLOGY
Incidence
• Highest incidence <2-yr-olds
• Males/females <1-yr-olds: 3–4%/2% develop UTI
• Males more likely to develop UTI in the first year of life then shifts to female predominance
Prevalence
Has not been delineated for each particular subpopulation/risk factor in the pediatric population
RISK FACTORS
• Previous UTI: 26% recur within 3 mo
• Metabolic abnormalities: Diabetes, pregnancy
• Impaired host response: Transplant, chemotherapy, HIV
– Neonates <90 days: Impaired immunity
• Structural anomalies
– Calculi, renal cysts, abscess, pyelonephritis, bladder diverticulum
– Urinary diversion, bladder augmentation
– Posterior urethral valves, reflux, prune belly, bladder exstrophy, urogenital sinus
• Uncircumcised males 10× risk of UTI
• Neurogenic bladder
• Intermittent catheterization: Increases rate of bacteriuria
– Single use, sterile catheters show no benefit
Genetics
• Polymorphisms of the interleukin-8 (IL-8) cytokine and decreased receptor expression increase risk for developing pyelonephritis
• Blood group antigen phenotype has been shown to play a role in UTI resistance
• Familial susceptibility to UTI
• Autosomal dominant inheritance of vesicoureteral reflux
• African Americans less likely to develop UTI when compared to whites, Hispanics
PATHOPHYSIOLOGY
• Fecal seeding of the perineum allows ascending infection of the GU tract
• Biofilm formation on stents or catheters
• Increased bladder pressure
– Decreased bladder capacity
– Compromised Foley catheter drainage
– Dysfunctional voiding
• Bacteriology of E. coli increase affinity for GU tract: P fimbriae and MRHA (mannose-resistant hemagglutination)
ASSOCIATED CONDITIONS
• Urinary stasis increases risk of UTI
• Stents or catheters located within the GU tract act as a nidus for bacterial colonization
• Surgically correctable conditions of the GU tract
• Spina bifida (1)
GENERAL PREVENTION
• Antibiotic prophylaxis
– Low-dose daily antibiotic
– Healthy children have no proven benefit
– Benefit for anatomic abnormality such as severe VUR
• Consider circumcision in boys <12 mo of age with GU tract anomalies
• Consider correction of vesicoureteral reflux (VUR) in females approaching puberty for increased risk of pyelonephritis during pregnancy
• Treatment of constipation and dysfunctional voiding
DIAGNOSIS
HISTORY
• Vague in infants and nonverbal children: Fever, irritability, poor feeding, vomiting, diarrhea, abdominal distention, new onset incontinence, jaundice.
• Older children: Dysuria, incontinence, voiding dysfunction, lower abdominal pain, enuresis
• Neurogenic bladder: Adominal pain, new onset back pain, new or worsening incontinence, pain with catheterization or urination, malodorous or cloudy urine
• Presence and severity of fever
• Previous UTIs and how documented (urine analysis, culture, how culture was obtained).
• Urinary stream, voiding history
• Previous GU/GI surgery
• Family history of infections and/or GU anomalies
• Prenatal history including ultrasounds
PHYSICAL EXAM
• Clinical signs of urosepsis
• Palpable bladder or kidneys, bladder or flank tenderness
• Foul smelling urine
• External genital anomalies: Labial adhesions, evidence of previous genital surgery
• Circumcision status
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Blood work: CBC, BMP, c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin
– Procalcitonin, CRP, ESR correlate with systemic illness and suggest pyelonephritis/sepsis
• Diagnosis: 2 or more symptoms, >100,000 CFU/mL of a single organism, and >10 WBC/HPF on urine microscopy
• Urinalysis (UA)
– Leukocyte esterase, nitrite
– Microscopy: WBC, bacteria
• Urine culture: obtained with UA
– Consider lower threshold (>50,000 CFUs per mL) PLUS pyuria ± bacteriuria in some cases
Imaging
• Renal and bladder ultrasound: Assess hydronephrosis or incomplete bladder emptying
• Voiding cystourethrogram if not already performed
– Document test of cure prior to study
• Renal cortical scan: Rule out scarring or pyelonephritis
– Consider Gallium scan for complicated cases
Diagnostic Procedures/Surgery
• Catheterized or midstream specimen is preferred depending upon patient age
– Suprapubic aspiration has highest accuracy but increases morbidity for patients
– Bagged specimen not recommended
• Cystoscopy is rarely indicated
– Can document bladder diverticulum, stones, etc., as source of UTI
• Specific intervention for GU anomalies (ie, treatment of reflux) once therapy is completed
Pathologic Findings
• Escherichia coli is the most common isolated organism although less so compared to uncomplicated UTI (45–51%)
• Proteus, Pseudomonas, and Candida are more commonly identified in complicated UTI
• Infants <90 days; Enterococcus and Listeria are most common organisms
DIFFERENTIAL DIAGNOSIS
• Younger children (<24 mo) presenting with fever: otitis media, gastroenteritis, upper respiratory tract infection
• Stone disease
• Urethritis
• Dysfunction voiding/elimination syndrome
• Pregnancy
• Appendicitis
• Bladder outlet obstruction
• Epididymitis
• Abuse
TREATMENT
GENERAL MEASURES (2,3)
• Antibiotic therapy after urine culture obtained
• Oral antibiotic therapy vs. IV antibiotics dependent upon severity of infection
– Stratify by presence or absence of fever, concern for urosepsis, elevated WBC, etc.
• Duration of therapy 7–14 days
• Increased rate of resistant organisms
MEDICATION
First Line
• 3rd-generation cephalosporin ± aminoglycoside
– Cefotaxime: 50–180 mg/kg/d (q4–6h)
– Ceftriaxone: 50–75 mg/kg/d (q12–24h)
– Ceftazidime: 90–150 mg/kg/d (q8–12h)
– Aminoglycoside (gentamicin, tobramycin): 7.5 mg/kd/d (q8h)
Enterococcus resistance to 3rd-generation cephalosporins
Second Line
• Fluoroquinolones
– Ciprofloxacin: 20–40 mg/kg/d (q8h)
Concern for cartilage damage limits its use in pediatric populations
• Carbapenem
• Combination therapy:
– Aminoglycoside plus β-lactam inhibitor
– Aminoglycoside plus fluoroquinolone
SURGERY/OTHER PROCEDURES
• Circumcision in boys with GU anomaly
• Correction of urologic anomaly if possible
• Removal of urinary stents or catheters if possible
• Video urodynamics to assess bladder emptying in particular if history of neurogenic bladder
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies (5)
• Targeted therapy for voiding dysfunction
– Timed voiding, biofeedback
– Anticholinergic medications for small, overactive bladder
• Pelvic floor therapy for detrusor sphincter dyssynergia
• Consider supressive antibiotics in selected cases: Nitrofurantoin 1–2 mg/kg PO daily, Sulfamethoxazole/trimethoprim (SMZ-TMP) 5–10 mg/kg SMZ,1–2 mg/kg TMP PO daily (Do not use nitrofurantoin or sulfa in children <6 weeks); Trimethoprim 1–2 mg/kg PO daily. Ampicillin or amoxicillin not recommended due to resistance
Complementary & Alternative Therapies (4)
• Ensure adequate hydration
• At home urine tests for families for early detection of UTI
• Breast feeding has been shown to confer protection during immune compromised neonatal period
• Cranberry juice/supplements show little, if any, benefit in the adult population; no data in children
• Probiotics have not been shown to prevent UTI
ONGOING CARE
PROGNOSIS
• Dependent upon severity of infection (febrile vs. afebrile, pyelonephritis, degree of subsequent renal scarring)
• While a single UTI rarely has long term sequelae, recurrent infections place the kidney at increased risk for damage
COMPLICATIONS
• Urosepsis
• Pyelonephritis
• Hypertension (HTN)
• Loss of renal function, progression of renal scarring
• Compromise of renal transplant
FOLLOW-UP
Patient Monitoring
• Document test of cure with repeat urine culture
• Yearly blood pressure assessment
• Consider nephrology referral
Patient Resources
American Association of Pediatrics. http://www.healthychildren.org/English/health-issues/conditions/genitourinary-tract/Pages/Detecting-Urinary-Tract-Infections.aspx
REFERENCES
1. Madden-Fuentes RJ, McNamara ER, Lloyd JC, et al. Variation in definitions of urinary tract infections in spina bifida patients: A systematic review. Pediatrics. 2013;132:132–139.
2. Younis N, Quol K, Al-Momani T, et al. Antibiotic resistance in children with recurrent or complicated urinary tract infection. JNMA. 2009;48(173):14–19.
3. Siomou E, Papadopoulou F, Kollios KD, et al. Duplex collecting system diagnosed during the first 6 years of life after a first urinary tract infection: A study of 63 children. J Urol. 2006;175(2):678–681.
4. Shortliffe LMD. Infection and Inflammation of the pediatric genitourinary tract. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology, 10th ed. Philadelphia, PA: Saunders; 2012.
5. Nickavar A, Sotoudeh K. Treatment and prophylaxis in pediatric urinary tract infection. Int J Prev Med. 2011;2(1):4–9.
ADDITIONAL READING
Subcommittee on urinary tract infection, steering committee on quality improvement and management. Urinary tract infection: Clinical guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2013;128(3):595–610.
See Also (Topic, Algorithm, Media)
• Urinary Tract Infection, Pediatric
• Urinary Tract Infection (UTI), Complicated, Pediatric Image 
• Vesicoureteral Reflux, Pediatric
CODES
ICD9
• 590.80 Pyelonephritis, unspecified
• 599.0 Urinary tract infection, site not specified
• 771.82 Urinary tract infection of newborn
ICD10
• N12 Tubulo-interstitial nephritis, not spcf as acute or chronic
• N39.0 Urinary tract infection, site not specified
• P39.3 Neonatal urinary tract infection
CLINICAL/SURGICAL PEARLS
• Complicated UTIs can lead to increased patient morbidity and mortality.
• Treatment plan should be tailored to the specific underlying contributing factors leading to UTI development.
• Prompt initiation of broad spectrum antibiotics after urine culture is obtained with subsequent tailoring of antibiotic therapy based on bacteria sensitivities is recommended in cases suspicious for urosepsis.
• Maintain a high degree of suspicion for potentially surgically correctable causes. Corrrection will likely decrease UTI risk.