The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"
The SCOUT Study: "Short Course Therapy for Urinary Tract Infections in Children"
The SCOUT study is a multi-center, centrally randomized, double-blind, placebo-controlled
 non-inferiority clinical trial. 746 participants will be enrolled over a 4.5 year period. 672
 will be evaluated for the study's primary outcome measure. After the first 5 days of primary
 care physician initiated antimicrobial therapy, patients who are afebrile and asymptomatic
 will then be randomized (1:1) to the standard course therapy arm of 5 more days of the same
 antibiotic therapy or the short course therapy arm of a placebo for 5 more days (for 10 days
 total). The primary objective of this study is to determine if halting antimicrobial therapy
 in subjects who have exhibited clinical improvement 5 days after starting antibiotic therapy
 (short course therapy) have the same failure rate (symptomatic UTI) through visit Day 11-14
 as subjects who continue to take antibiotics for an additional 5 days (standard course
 therapy).
The SCOUT Study is a multi-center, centrally randomized, double-blind, placebo-controlled
 non-inferiority clinical trial of 746 children ages two months (at least 36 weeks gestation
 from birth for subjects < two years of age) to 10 years with a confirmed diagnosis of a
 urinary tract infection (UTI) to evaluate 672 for the study's primary outcome measure. UTI is
 one of the most common serious bacterial infections during childhood. Escherichia coli (E.
 coli) isolates account for 80-90 percent of all outpatient UTIs in children. Although
 antibiotics are the first treatment choice for urinary tract infections, antibiotic-resistant
 strains of E. coli, the most common cause of UTIs, are increasing worldwide. The study will
 enroll 746 children who have demonstrated clinical improvement five days after starting the
 originally prescribed antibiotic (afebrile and asymptomatic) and they will be randomized
 either to the standard-course arm or the short-course arm at a 1:1 ratio. Subjects will be
 enrolled over approximately a four and a half year period. Study duration for each individual
 subject will be approximately five weeks. The study product will consist of
 trimethoprim-sulfamethoxazole (TMP-SMX), cefixime, cefdinir, cephalexin and the corresponding
 placebos. The primary objective of this study is to determine if halting antimicrobial
 therapy in subjects who have exhibited clinical improvement 5 days after starting antibiotic
 therapy (short course therapy) have the same failure rate (symptomatic UTI) through visit Day
 11-14 as subjects who continue to take antibiotics for an additional 5 days (standard course
 therapy). The secondary objectives are: 1) to determine if short-course therapy compared to
 standard course therapy results in similar numbers of children experiencing a recurrent
 urinary tract infection (relapse and reinfection; 2) to determine if short-course therapy
 compared to standard course therapy results in similar numbers of children with asymptomatic
 bacteriuria; 3) to determine if short-course therapy compared to standard course therapy
 results in similar numbers of children with gastrointestinal colonization of antimicrobial
 resistant Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumoniae); 4) to
 determine if short-course therapy compared to standard course therapy results in similar
 numbers of subjects presenting with clinical symptoms that may be related to UTI; 5) to
 determine if the number of subjects with positive urine culture prior to or at visit Day
 11-14 is similar after short-course therapy compared to standard course therapy.
Inclusion Criteria:

 1. Age at randomization: at least two months (at least 36 weeks gestational age for
 subjects less than two years of age) to 10 years of age (120 months).

 2. Confirmed UTI (Urinary Tract Infection) diagnosis.

 3. Documented Clinical Improvement at Randomization.

 1. Afebrile: No documented temperature > / = 100.4 degrees Fahrenheit or 38 degrees
 Celsius (measured anywhere on the body) 24 hours prior to the enrollment visit

 2. Asymptomatic: report NONE of the following symptoms:

 -  Symptoms for all children (ages two months to 10 years):

 -  Fever (a documented temperature of at least 100.4 degrees Fahrenheit OR
 38 degrees Celsius measured anywhere on the body)

 -  dysuria

 -  Additional symptoms for children > 2 years of age:

 -  suprapubic, abdominal, or flank pain or tenderness OR

 -  urinary urgency, frequency, or hesitancy (defined as an increase in
 these symptoms from pre-diagnosis conditions)

 -  Additional symptoms for children > / = 2 months to 2 years of age:

 -  poor feeding OR

 -  vomiting

 4. Only children who have been prescribed one of the four antibiotics for which a placebo
 is available will be eligible to participate.

 -  TMP-SMX; Cefixime; Cefdinir or Cephalexin. (Note a child that received a one-time
 dose of I.M. or I.V. medication (i.e. in ER or clinic) prior to starting on the
 one of the four oral medications is eligible for enrollment)

 5. Parental or guardian permission (informed consent) and if appropriate, child assent
 (if > / = seven years of age).

 Exclusion Criteria:

 1. A urine culture proven infection with a second uropathogen > 10,000 CFU/mL collected
 via suprapubic aspiration or catheter or > 50,000 CFU/mL collected via clean void.

 2. A child hospitalized with a UTI that has the following: concomitant bacteremia
 associated with the UTI, urosepsis, or is in intensive care.

 3. A child whose urine culture reveals an organism that is resistant to the initially
 prescribed antibiotic.

 4. A child with a catheter-associated UTI.

 5. A child with known anaphylactic allergies to the study products.

 6. A child with phenylketonuria (PKU).

 7. A child diagnosed with congenital anomalies of the genitourinary tract.

 8. UTI in children with known anatomic abnormalities of the genitourinary tract other
 than VUR (Vesicoureteral reflux), duplicated collection systems, and hydronephrosis.

 9. A child that is not able to take oral medications.

 10. Previous surgery of the genitourinary tract (except circumcision in male children).

 11. Presence of an immunocompromising condition (e.g., HIV, malignancy, solid-organ
 transplant recipients, use of chronic corticosteroids or other immunosuppressive
 agents).

 12. Unlikely to complete follow-up (e.g. not available for the two follow-up study visits
 and the follow-up phone call).

 13. A child with a known history of type I hypersensitivity of the study antibiotics to be
 prescribed .

 14. Enrollment in another antibiotic study less than 30 days prior to enrollment visit.

 15. Previous enrollment of individuals in this study.

 16. Planned enrollment during this study coincides with enrollment in another therapeutic
 drug study (excluding vaccine).

 17. A child with a history of UTI within the past 30 days.

 18. A child with known Grade III-V VUR.

 19. A child taking antibiotic prophylaxis for any reason.

 20. A child who has started Day 6 of the originally prescribed antibiotic treatment.