Urinary Tract Infection
Conditions
Keywords
antibiotic therapy, antimicrobial resistance, children, E.coli, K.pneumoniae, parent study, SCOUT Study, spectrum stool bacteria, stool culture, urinary tract infections
Brief summary
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).
Detailed description
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.
Interventions
DRUGCefixime
Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime.
DRUGCephalexin
Cephalexin 50mg/kg/day in 3 divided doses
OTHERPlacebo
Placebo to match the other four active treatments
8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Months to 10 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. | Day 11 through Day 14 | A subject will be categorized as a treatment failure, if he/she has a symptomatic UTI in period between Day 6 through the Day 11 - 14 Test of Cure (TOC) Visit: 1. Symptoms * Symptoms for all subjects (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) ,dysuria * Additional symptoms for subjects \> 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 subjects = 2 months to 2 years of age: poor feeding OR vomiting AND 2. Pyuria on urinalysis AND 3. Culture proven infection with a single uropathogen NOTE: As per the above criteria, asymptomatic subjects (including subjects assessed as having asymptomatic bacteriuria) at the Day 11-14 TOC visit will NOT be considered a treatment failure for the primary outcome measure. |
| Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population. | Day 11 through Day 14 | A subject will be categorized as a treatment failure, if he/she has a symptomatic UTI in period between Day 6 through the Day 11 - 14 Test of Cure (TOC) Visit: 1. Symptoms * Symptoms for all subjects (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) ,dysuria * Additional symptoms for subjects \> 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 subjects = 2 months to 2 years of age: poor feeding OR vomiting AND 2. Pyuria on urinalysis AND 3. Culture proven infection with a single uropathogen NOTE: As per the above criteria, asymptomatic subjects (including subjects assessed as having asymptomatic bacteriuria) at the Day 11-14 TOC visit will NOT be considered a treatment failure for the primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. | Day 11 through Day 30 | A child would have emergent antibiotic resistance if they: 1. Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR 2. Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR 3. Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism. |
| Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population. | Day 11 through Day 30 | A child would have emergent antibiotic resistance if they: 1. Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR 2. Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR 3. Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism. |
| Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. | Day 11 through Day 14 | Asymptomatic Bacteriuria is defined in any SCOUT subject by: 1. Absence of symptoms attributable to UTI including fever AND/OR the following: * Symptoms for all children (ages two months to 10 years): * fever (a documented temperature of at least 100.4 °F OR 38°C 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 AND 2. A positive urine culture * 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR * \>105 CFU/mL (clean void specimen). |
| Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | Day 11 through Day 14 | Asymptomatic Bacteriuria is defined in any SCOUT subject by: 1. Absence of symptoms attributable to UTI including fever AND/OR the following: * Symptoms for all children (ages two months to 10 years): * fever (a documented temperature of at least 100.4 °F OR 38°C 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 AND 2. A positive urine culture * 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR * \>105 CFU/mL (clean void specimen). |
| Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. | Day 11 through Day 44 | — |
| Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population | Up to Day 14 | — |
| Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. | Up to Day 14 | — |
| Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | Up to Day 14 | — |
| Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. | Up to Day 14 | — |
| Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | Day 11 through Day 44 | — |
Countries
United States
Participant flow
Pre-assignment details
Of the 717 enrolled, 23 did not meet the screening criteria and 1 withdrew consent prior to randomization. 693 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Standard Course Treatment 5 days of active therapy to match the physician-initiated therapy, Trimethoprim sulfamethoxazole, Cefixime or Cefdinir or Cephalexin (subjects originally receiving Cefdinir will receive Cefixime)
Cefixime: Cefixime 8 mg/kg/day orally, in 1 dose, with a maximum of 400 mg. Subjects originally receiving Cefdinir will receive Cefixime.
Cephalexin: Cephalexin 50mg/kg/day in 3 divided doses
Trimethoprim/Sulfamethoxazole: 8 mg/kg/day of Trimethoprim-sulfamethoxazole (TMP-SMX) orally in 2 divided doses, with a maximum dose of 160 mg twice a day. | 328 |
| Short Course Treatment 5 days of placebo treatment to match physician-initiated therapy
Placebo: Placebo to match the other four active treatments | 336 |
| Total | 664 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative Decision | 1 | 0 |
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Consent Withdrawn/Voluntary Withdrawal | 3 | 3 |
| Overall Study | Entry Failure/Screening Failure | 6 | 1 |
| Overall Study | Lost to Follow-up | 8 | 14 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Subject Non-Compliant | 2 | 0 |
Baseline characteristics
| Characteristic | Short Course Treatment | Standard Course Treatment | Total |
|---|---|---|---|
| Age, Continuous | 4.16 years STANDARD_DEVIATION 2.62 | 4.31 years STANDARD_DEVIATION 2.71 | 4.23 years STANDARD_DEVIATION 2.66 |
| Age, Customized Age 2 months - 35 months | 89 Participants | 95 Participants | 184 Participants |
| Age, Customized Age 3 - 6 years | 177 Participants | 148 Participants | 325 Participants |
| Age, Customized Age 7 - 10 years | 70 Participants | 85 Participants | 155 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic | 27 Participants | 33 Participants | 60 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic | 309 Participants | 295 Participants | 604 Participants |
| Race/Ethnicity, Customized Race American Indian/Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 8 Participants | 5 Participants | 13 Participants |
| Race/Ethnicity, Customized Race Black/African American | 83 Participants | 73 Participants | 156 Participants |
| Race/Ethnicity, Customized Race Multi-Racial | 25 Participants | 23 Participants | 48 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian/Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Other | 6 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 210 Participants | 217 Participants | 427 Participants |
| Sex: Female, Male Female | 323 Participants | 316 Participants | 639 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 328 | 0 / 336 |
| other Total, other adverse events | 155 / 328 | 147 / 336 |
| serious Total, serious adverse events | 2 / 328 | 4 / 336 |
Outcome results
Primary
Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics.
A subject will be categorized as a treatment failure, if he/she has a symptomatic UTI in period between Day 6 through the Day 11 - 14 Test of Cure (TOC) Visit: 1. Symptoms * Symptoms for all subjects (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) ,dysuria * Additional symptoms for subjects \> 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 subjects = 2 months to 2 years of age: poor feeding OR vomiting AND 2. Pyuria on urinalysis AND 3. Culture proven infection with a single uropathogen NOTE: As per the above criteria, asymptomatic subjects (including subjects assessed as having asymptomatic bacteriuria) at the Day 11-14 TOC visit will NOT be considered a treatment failure for the primary outcome measure.
Time frame: Day 11 through Day 14
Population: Intent to treat population, ITT. All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. | 2 Participants |
| Short Course Treatment | Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. | 14 Participants |
Primary
Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population.
A subject will be categorized as a treatment failure, if he/she has a symptomatic UTI in period between Day 6 through the Day 11 - 14 Test of Cure (TOC) Visit: 1. Symptoms * Symptoms for all subjects (ages two months to 10 years): fever (a documented temperature of at least 100.4 °F OR 38°C measured anywhere on the body) ,dysuria * Additional symptoms for subjects \> 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 subjects = 2 months to 2 years of age: poor feeding OR vomiting AND 2. Pyuria on urinalysis AND 3. Culture proven infection with a single uropathogen NOTE: As per the above criteria, asymptomatic subjects (including subjects assessed as having asymptomatic bacteriuria) at the Day 11-14 TOC visit will NOT be considered a treatment failure for the primary outcome measure.
Time frame: Day 11 through Day 14
Population: Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population. | 2 Participants |
| Short Course Treatment | Comparison of Efficacy Based on Symptomatic Urinary Tract Infection (UTI) Between Short-course and Standard-course of Antibiotics. Per-protocol Population. | 9 Participants |
Secondary
Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics.
Time frame: Day 11 through Day 44
Population: Subjects in the ITT population who did not experience a treatment failure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. | 12 Participants |
| Short Course Treatment | Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. | 13 Participants |
95% CI: [-0.03323, 0.026102]
Secondary
Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population.
Time frame: Day 11 through Day 44
Population: Subjects in the per-protocol population who did not experience a treatment failure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | 10 Participants |
| Short Course Treatment | Comparison of Number of Subjects That Have a Recurrent Infection (Includes a Relapse UTI or a Reinfection) Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | 13 Participants |
95% CI: [-0.04012, 0.020236]
Secondary
Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population.
A child would have emergent antibiotic resistance if they: 1. Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR 2. Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR 3. Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism.
Time frame: Day 11 through Day 30
Population: Subjects in the ITT population who have a stool sample at TOC visit. Some treatment failures will not have a sample collected at TOC because they failed prior to TOC. Treatment failures without the sample at TOC would be excluded from the Antibiotic Resistant ITT population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population. | Test of Cure Visit (Day 11-14) | 22 Participants |
| Standard Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population. | Outcome Assessment Visit (Day 24-30) | 23 Participants |
| Short Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population. | Test of Cure Visit (Day 11-14) | 28 Participants |
| Short Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant E. Coli and K. Pneumoniae in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. Per-protocol Population. | Outcome Assessment Visit (Day 24-30) | 23 Participants |
Comparison: At Test of Cure Visitp-value: 0.4184Chi-squared
Comparison: At Outcome Assessment Visitp-value: 0.9782Chi-squared
Secondary
Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics.
A child would have emergent antibiotic resistance if they: 1. Had no antibiotic-resistant E.coli or K.pneumoniae at enrollment but one or both are now present. OR 2. Had either antibiotic-resistant E.coli or K.pneumoniae at enrollment but now the other antibiotic-resistant organism is present OR 3. Had antibiotic-resistant E.coli and/or K.pneumoniae at enrollment, but have now developed resistance to new antibiotics in either organism.
Time frame: Day 11 through Day 30
Population: Subjects in the ITT population who have a stool sample at TOC visit. Some treatment failures will not have a sample collected at TOC because they failed prior to TOC. Treatment failures without the sample at TOC are excluded.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. | Outcome Assessment Visit (Day 24-30) | 23 Participants |
| Standard Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. | Test of Cure Visit (Day 11-14) | 22 Participants |
| Short Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. | Test of Cure Visit (Day 11-14) | 31 Participants |
| Short Course Treatment | Comparison of the Number of Subjects That Become Colonized With Antimicrobial Resistant Escherichia Coli (E. Coli) and Klebsiella Pneumoniae (K. Pneumoniae) in the Gastrointestinal Tract Following Short-course Versus Standard Course of Antibiotics. | Outcome Assessment Visit (Day 24-30) | 28 Participants |
Comparison: At Test of Cure Visitp-value: 0.2282Chi-squared
Comparison: At Outcome Assessment Visitp-value: 0.4876Chi-squared
Secondary
Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics.
Asymptomatic Bacteriuria is defined in any SCOUT subject by: 1. Absence of symptoms attributable to UTI including fever AND/OR the following: * Symptoms for all children (ages two months to 10 years): * fever (a documented temperature of at least 100.4 °F OR 38°C 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 AND 2. A positive urine culture * 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR * \>105 CFU/mL (clean void specimen).
Time frame: Day 11 through Day 14
Population: Intent-to-treat (ITT) Population: All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. | 11 Participants |
| Short Course Treatment | Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. | 29 Participants |
95% CI: [-0.08857, -0.01698]
Secondary
Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population.
Asymptomatic Bacteriuria is defined in any SCOUT subject by: 1. Absence of symptoms attributable to UTI including fever AND/OR the following: * Symptoms for all children (ages two months to 10 years): * fever (a documented temperature of at least 100.4 °F OR 38°C 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 AND 2. A positive urine culture * 5 x 104 CFU/mL (catheterized or suprapubic aspiration urine specimen) OR * \>105 CFU/mL (clean void specimen).
Time frame: Day 11 through Day 14
Population: Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | 11 Participants |
| Short Course Treatment | Comparison of the Number of Subjects With Asymptomatic Bacteriuria Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | 29 Participants |
95% CI: [-0.09479, -0.0185]
Secondary
Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics.
Time frame: Up to Day 14
Population: Intent-to-treat (ITT) Population: All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. | 30 Participants |
| Short Course Treatment | Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. | 41 Participants |
95% CI: [-0.07744, 0.016323]
Secondary
Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population
Time frame: Up to Day 14
Population: Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population | 29 Participants |
| Short Course Treatment | Comparison of the Number of Subjects With Clinical Symptoms That May be Related to a UTI Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population | 33 Participants |
95% CI: [-0.058, 0.036117]
Secondary
Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics.
Time frame: Up to Day 14
Population: Intent-to-treat (ITT) Population: All subjects taking at least one dose of study treatment between Day 6 and Day 10 who have been evaluated for treatment success at TOC or have failed prior to TOC.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. | 6 Participants |
| Short Course Treatment | Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. | 41 Participants |
95% CI: [-0.14161, -0.06585]
Secondary
Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population.
Time frame: Up to Day 14
Population: Per-protocol Population (PP): The enrolled subjects who were adherent to their assigned study regimen and completed more than 80% of the prescribed dose between Day 6 and Day 10 (per-protocol population).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Course Treatment | Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | 6 Participants |
| Short Course Treatment | Comparison of the Number of Subjects With Positive Urine Cultures Following Short-course Versus Standard-course of Antibiotics. Per-protocol Population. | 35 Participants |
95% CI: [-0.13006, -0.05391]