Urinary Tract Infection (UTI)

Objectives
Define UTI Discuss prevalence of UTI in pediatric patients Name predominant causative pathogens List empiric and pathogen-specific therapies Discuss rationale and appropriate antibiotic choice for prophylaxis therapy

UTI: Definition
Significant bacteriuria in presence of symptoms at any level of urinary tract:

- Bladder: cystitis - Renal pelvis: pyelitis

- Urethra: urethritis - Renal parenchyma: pyelonephritis

UTI Terminology
Uncomplicated: infection of urinary bladder in host
w/out underlying renal or neurologic disease structural, medical or neurologic disease

Complicated: infection in setting of underlying Recurrent: > 2 symptomatic UTIs w/in 12 month Reinfection: recurrent UTI caused by a different
following clinical resolution of each previous UTI after therapy pathogen at any time or original infecting strain >13 days after therapy of original UTI original UTI w/in 2 wks after therapy

Relapse: recurrent UTI caused by same species causing

Pathogenesis
For optimal host defense function, intermittent & complete emptying of bladder must occur
Urine is excellent culture medium Bactericidal secretion from uroepithelial cells and glycoproteins inhibit bacterial adherence

Ascending bacterial infection Hematogenous spread to kidney is rare Renal parenchyma infections result in inflammatory response to contain infection but contributes to potential scarring

Complications
Pediatric UTIs are associated with significant morbidity
Renal scarring: 20% to 30% Hypertension: 10%

Contribution of vesicoureteral reflux, recurrent UTIs, and renal scars to development of end stage renal disease is unclear
ESRD: 1%

Complications: Relationship of Renal Scarring and No. of UTIs

Pediatrics. 1999; 103; 843-852

Vesicoureteral Reflux (VUR)

Primary reflux: congenital abnormality of insertion of ureter through the bladder wall
> 80% spontaneous resolve by first decade of life

Secondary reflux: develops from elevated intravesicular pressure from abnormal voiding patterns or anomalies (eg obstruction)
Resolution less predictable and based on treating underlying cause

Incidence
General population: 1%-2% < 1 year with UTI: 70% Adolescent with UTI: 5%

VUR: Prevalence by Age

Pediatrics. 1999; 103; 843-852

Prevalence
Neonates: males > females Febrile infants 2-24 months1: Male Female
*Circumcised 0.2%

< 1 year 3%* 7%

1 year 2% 8%

Bacteremia:
0-3 mos: 10% of febrile infants

Recurrence: up to 80%
1

American Academy of Pediatrics, Technical Report: UTI in febrile infants and young children

Risk Factors
Conditions interfere with complete bladder emptying
Neurogenic bladder Voiding dysfunction

Prolonged catheter placement Anatomical abnormalities

Posterior urethral valves Ureterocele Vesicoureteral reflux

Sexually active adolescent girls

Clinical Manifestations
Uncomplicated Dysuria Urgency Low-grade fever Frequency Suprapubic discomfort Daytime or noctural enuresis Complicated High fever Chills Flank and/or abdominal pain Nausea Vomiting +/- lower urinary tract symptoms

Diagnosis
Methods of urine collection
Suprapubic aspirate (SPA) Bladder catheterization Clean-catch midstream collection Clean-bagged specimen: only excludes diagnosis if (-)

Urine culture is gold standard

Isolation of single pathogen in culture of 100,000 colonies/ml

Urinalysis dipstick
Hemoglobin test strip Leukocyte esterase: (+) WBC Nitrite: (+) gram-negative bacteria

Gram stain: reliable screening tool

Pathogens
Type of infection Complicated Organisms Escherichia coli Enterococcus Psuedomonas aeruginosa Escherichia coli Staphylococcus saprophyticus Enterobacter spp. Klebsiella spp. Proteus spp.

Uncomplicated

Treatment Considerations
Allergies Age of patient Empiric therapy Pathogen specific therapy Duration of therapy Compliance Prophylaxis

Treatment Considerations
If any of the following conditions are met, patient should be admitted to hospital:
Failed oral re-hydration Toxic or ill-appearing Failed previous outpatient therapy Uncertainty of outpatient care

Inpatient Treatment
Emperic coverage Gentamicin 6-7.5 mg/kg/day IV Q8hr or Qday
or

Ceftriaxone 50 mg/kg IV/IM Qday AND Amipicillin 100-200 mg/kg IV Q6hr After 48 hours
If response: switch to appropriate PO therapy and treat for total of 7-14 days If no response: renal US along with VCUG or RNC and tailored therapy to culture results is recommended if no response after 48 hours

Pathogen-Specific Treatment
Pathogen Treatment options Escherichia coli Ceftriaxone 50 mg/kg IV/IM Qday Psuedomonas aerginosa Gentamicin 6-7.5 mg/kg IV Enterobacter spp. Q8hr or Qday Klebsiella spp. Ceftazidime 100-150 mg/kg/day Proteus spp. IV Q8hr Enterococcus
Ampicillin 100-200 mg/kg/day IV Q6hr

Outpatient Therapy
Considerations for oral therapy
Spectrum of activity Tolerability Bioavailability Urinary concentration

Length of therapy
Complicated: 14 days Uncomplicated: 5-10 days

Treatment Options
Antibiotic Dosing Trimethoprim/sulfamethoxazole 6-12 mg TMP/kg/day PO BID (Bactrim) Nitrofurantoin (Macrodantin) Cefixime (Suprax) Cephalexin (Keflex) Amoxicillin (Amoxil) 5-7 mg/kg/day PO QDay 16 mg/kg/day PO x 1 day 8 mg/kg/dayn PO BID 25-50 mg/kg/day PO TID 40 mg/kg/day PO TID

Sulfamethoxazole/Trimethoprim
Class: sulfonamide Adverse events
Anemia, thrombocytopenia Increased LFTs Nausea/vomiting Stevens-Johnson Syndrome Contraindications
Hypersensitivity to sulfa drugs or trimethoprim Infants <2 months Megaloblastic anemia

Dosage forms
Injection Suspension Tablet

Palatability: tolerable

Nitrofurantoin
Class: miscellaneous Adverse events
Rash Discoloration of urine Pancytopenia Nausea Vomiting Discoloration of urine (dark yellow or brown)

Contraindications
Hypersensitivity to nitrofurantoin Renal impairment Neonates

Dosage forms
Suspension Capsule

Palatability: tolerable

Cefixime
Class: cephalosporin (3rd generation) Adverse events:
Rash, urticaria Nausea Diarrhea Thrombocytopenia, leukopenia Elevated LFTs

Contraindications: hypersensitivity to cephalosporins Dosage forms

Suspension

Palatability: excellent

Cephalexin
Class: cephalosporin (1st generation) Adverse events
Rash Nausea Vomiting Transient neutropenia, thrombocytopenia

Contraindications
Hypersensitivity to cephalosporins

Dosage forms
Capsule Tablet Suspension

Palatability: excellent

Amoxicillin
Class: penicillin Adverse events:
Rash Diarrhea Nausea Vomiting Elevated LFTs

Contraindications
Hypersensitivity to penicillin

Dosage forms
Capsule Tablet Suspension

Palatability: excellent

Prophylaxis
Prophylactic therapy should be prescribed for children:
Awaiting VCUG following first UTI until normal anatomy is demonstrated Known to have VUR, partial obstruction or voiding dysfunction Children with frequent recurrent UTIs who have anatomically normal urinary tracts
>2 in a 6-month period

Prophylaxis
Antibiotic Sulfamethoxazole/ Trimethoprim Trimethoprim Amoxicillin Cephalexin Nitrofurantoin Prophylactic Dose 2 mg/kg/day PO Daily 2 mg/kg/day PO Daily 10 mg/kg/day PO Daily 10 mg/kg/day PO Daily 1-2.5 mg/kg/day PO Daily

Questions?