Acute Otitis Media, Acute Sinusitis, Group A Streptococcal Pharyngitis
Conditions
Keywords
antibiotic use, effectiveness, acute respiratory infections, pediatrics
Brief summary
The purpose of this study is to identify and use patient centered outcomes to compare narrow-spectrum and broad-spectrum antibiotics for the treatment of common acute respiratory tract infections (ARTIs) in children.
Detailed description
Outpatient, ARTIs account for the vast majority of antibiotic exposure to children, and roughly half of these antibiotic prescriptions are inappropriate. Although unnecessary antibiotic prescribing for viral infections has significantly decreased, there has been a substantial increase in prescribing of broad-spectrum antibiotics to treat ARTIs when narrow-spectrum antibiotics are indicated. Primary care providers, patients, and caregivers would benefit from studies assessing the implications of alternate antibiotic regimens for these common infections. Specifically, it remains unclear if treating common ARTIs with broad-spectrum antibiotics leads to an improvement in patient outcomes compared to treatment with narrow-spectrum antibiotics, particularly considering the increasing threat posed by antimicrobial resistance. Because of the lack of large comparative effectiveness studies with patient-centered outcomes addressing this issue, professional guidelines and expert recommendations are conflicting, and, as a result, practice patterns vary considerably. Therefore, using patient-centered outcomes, we aim to compare narrow-spectrum and broad-spectrum antibiotics for the treatment of common ARTIs in children. To accomplish this, we will perform a prospective cohort study of children receiving antibiotics for ARTI across a comprehensive pediatric healthcare network. We will conduct telephone interviews with parent's of children who receive antibiotic treatment for an ARTI. We will assess previously identified patient-centered outcomes included a health-related quality of life measure, occurrence of side effects, missed school/daycare, parent missed commitments and/or required additional childcare and symptoms were still present on day 3 after diagnosis.
Interventions
Amoxicillin-clavulanate, azithromycin, cefdinir, cefprozil, cefuroxime axetil, cefadroxil, cephalexin
DRUGNarrow-spectrum antibiotics
Amoxicillin, Penicillin
Sponsors
Children's Hospital of Philadelphia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to 12 Years
Healthy volunteers
No
Inclusion criteria
We included children between six months and 12 years old, diagnosed with an ARTI (acute otitis media, acute sinusitis, Group A streptococcal \[GAS\] pharyngitis) using International Classification of Diseases diagnosis codes and prescribed an antibiotic. For GAS pharyngitis, the child also had a positive rapid streptococcal test.
Exclusion criteria
* Diagnosed with multiple ARTIs * Diagnosed with another non-ARTI bacterial infection * Prescribe antibiotics in the past 30 days * Non-English speaking families * If GAS pharyngitis diagnosis, age \< 3 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health Related Quality of Life Score | 5-10 days after ARTI diagnosis | The health related quality of life score was obtained using the PedsQL(TM) (Mapi Research Trust, Lyon, France. www.pedsql.org) Parent-Proxy Report Generic Core Scales and Parent Report Infant Scales administered during the 5-10 day interview. Briefly, the PedsQL(TM) is a 23-item questionnaire assessing developmentally appropriate metrics (questions vary by age group: 1-12 months, 13-24 months, 2-4 years, 5-7 years, 8-12 years) related to core dimensions of health and role functioning. Our primary outcome was the Total Scale Score, which is a summary score of physical, emotional, social, and school functioning. The score range is zero to 100 and higher scores indicate a better health-related quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Missed School or Daycare From Illness | 5-10 days after ARTI diagnosis | Among children who attend school or daycare, child had to miss school or day care due to illness |
| Required Additional Childcare | 5-10 days after ARTI diagnosis | Among children who attend school or daycare, parent or another caretaker had to miss work or an obligation due to child's illness OR additional childcare had to be sought for the child. |
| Experience Side Effects | 14-20 days after ARTI diagnosis | Child experienced a side effect including: rash, diarrhea or upset stomach/vomiting |
| Symptoms Present on Day 3 | 3 days after ARTI diagnosis | During 5-10 day interview, parents were asked about symptoms related to child's illness (otitis media: fever, ear pain, decreased appetite; sinusitis: fever, face/head pain, decreased appetite; pharyngitis: throat pain, fever, decreased appetite). Parent was asked if symptoms was present at diagnosis. If yes, had the symptom resolved. If yes, when. We assessed whether symptoms present at day 3 after diagnosis. |
| Sleep Disturbance | Days 5-10 Interview | The PedsQL questionnaire includes one or two questions, depending on age, about sleep. For children \<24 months, parents are asked the frequency (never, almost never, sometimes, often, almost always) their child has (1) difficulty falling asleep and (2) difficulty sleeping through the night. For children ≥2 years, parents are asked the frequency their child has trouble sleeping. We categorized children as either without sleep disturbance (Never for each sleep question) or with sleep disturbance. Outcome measure shows the number of participants with sleep disturbance. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Narrow Spectrum Antibiotics Child prescribed with the following at time of diagnosis:
Acute otitis media: Amoxicillin Acute sinusitis: Amoxicillin Streptococcal pharyngitis: Penicillin or Amoxicillin | 1,604 |
| Non-narrow Spectrum Antibiotics Child prescribed with the following at time of diagnosis:
Acute otitis media: Amoxicillin-Clavulanate, Azithromycin, Cefdinir, Cefprozil, Cefuroxime Axetil Acute sinusitis: Amoxicillin-Clavulanate, Azithromycin, Cefdinir, Cefprozil, Cefuroxime Axetil Streptococcal pharyngitis: Amoxicillin-Clavulanate, Azithromycin, Cefadroxil, Cefdinir, Cefprozil, Cefuroxime Axetil, Cephalexin | 868 |
| Total | 2,472 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 236 | 140 |
Baseline characteristics
| Characteristic | Total | Narrow Spectrum Antibiotics | Non-narrow Spectrum Antibiotics |
|---|---|---|---|
| Age, Continuous | 4.96 Years STANDARD_DEVIATION 3.53 | 4.83 Years STANDARD_DEVIATION 3.51 | 5.19 Years STANDARD_DEVIATION 3.56 |
| Race/Ethnicity, Customized Race/Ethnicity Black (non-latino or unknown ethnicity) | 580 Participants | 474 Participants | 106 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Latino/hispanic | 212 Participants | 147 Participants | 65 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other (non-latino/unknown ethnicity) | 188 Participants | 129 Participants | 59 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Unknown race and unknown ethnicity | 41 Participants | 33 Participants | 8 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White (non-latino or unknown ethnicity) | 1451 Participants | 821 Participants | 630 Participants |
| Region of Enrollment United States | 2472 Participants | 1604 Participants | 868 Participants |
| Sex: Female, Male Female | 1197 Participants | 774 Participants | 423 Participants |
| Sex: Female, Male Male | 1275 Participants | 830 Participants | 445 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,604 | 0 / 868 |
| other Total, other adverse events | 345 / 1,367 | 258 / 726 |
| serious Total, serious adverse events | 0 / 1,604 | 0 / 868 |
Outcome results
Primary
Health Related Quality of Life Score
The health related quality of life score was obtained using the PedsQL(TM) (Mapi Research Trust, Lyon, France. www.pedsql.org) Parent-Proxy Report Generic Core Scales and Parent Report Infant Scales administered during the 5-10 day interview. Briefly, the PedsQL(TM) is a 23-item questionnaire assessing developmentally appropriate metrics (questions vary by age group: 1-12 months, 13-24 months, 2-4 years, 5-7 years, 8-12 years) related to core dimensions of health and role functioning. Our primary outcome was the Total Scale Score, which is a summary score of physical, emotional, social, and school functioning. The score range is zero to 100 and higher scores indicate a better health-related quality of life.
Time frame: 5-10 days after ARTI diagnosis
Population: 1 subject did not respond to enough of the questions to obtain a score; 41 children missing race and ethnicity were excluded
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Narrow Spectrum Antibiotic | Health Related Quality of Life Score | 91.5 scores on a scale | Standard Deviation 9.3 |
| Broad Spectrum Antibiotic | Health Related Quality of Life Score | 90.2 scores on a scale | Standard Deviation 10.5 |
Comparison: Propensity-score based full matching performed using patient and physician-level characteristics. Average treatment effect weights calculated and applied to a weighted linear regression.p-value: 0.00895% CI: [-2.44, -0.36]Weighted linear regression
Secondary
Experience Side Effects
Child experienced a side effect including: rash, diarrhea or upset stomach/vomiting
Time frame: 14-20 days after ARTI diagnosis
Population: Question was asked in the 14-20 interview so some subjects were lost to follow-up; 41 children missing race and ethnicity were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Narrow Spectrum Antibiotic | Experience Side Effects | 341 Participants |
| Broad Spectrum Antibiotic | Experience Side Effects | 258 Participants |
Comparison: Propensity-score based full matching performed using patient and physician-level characteristics. Average treatment effect weights calculated and applied to a weighted logistic regression. Risk difference obtained by marginal standardization.p-value: <0.00195% CI: [7.3, 17.2]Weighted logistic regression
Secondary
Missed School or Daycare From Illness
Among children who attend school or daycare, child had to miss school or day care due to illness
Time frame: 5-10 days after ARTI diagnosis
Population: Among children who attend school or daycare; 41 children missing race and ethnicity were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Narrow Spectrum Antibiotic | Missed School or Daycare From Illness | 503 Participants |
| Broad Spectrum Antibiotic | Missed School or Daycare From Illness | 305 Participants |
Comparison: Propensity-score based full matching performed using patient and physician-level characteristics. Average treatment effect weights calculated and applied to a weighted logistic regression. Risk difference obtained by marginal standardization.p-value: 0.3995% CI: [-3.1, 7.9]Weighted logistic regression
Secondary
Required Additional Childcare
Among children who attend school or daycare, parent or another caretaker had to miss work or an obligation due to child's illness OR additional childcare had to be sought for the child.
Time frame: 5-10 days after ARTI diagnosis
Population: Among children who attend school or daycare; 41 children missing race and ethnicity were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Narrow Spectrum Antibiotic | Required Additional Childcare | 390 Participants |
| Broad Spectrum Antibiotic | Required Additional Childcare | 220 Participants |
Comparison: Propensity-score based full matching performed using patient and physician-level characteristics. Average treatment effect weights calculated and applied to a weighted logistic regression. Risk difference obtained by marginal standardization.p-value: 0.5995% CI: [-3.9, 6.8]Weighted logistic regression
Secondary
Sleep Disturbance
The PedsQL questionnaire includes one or two questions, depending on age, about sleep. For children \<24 months, parents are asked the frequency (never, almost never, sometimes, often, almost always) their child has (1) difficulty falling asleep and (2) difficulty sleeping through the night. For children ≥2 years, parents are asked the frequency their child has trouble sleeping. We categorized children as either without sleep disturbance (Never for each sleep question) or with sleep disturbance. Outcome measure shows the number of participants with sleep disturbance.
Time frame: Days 5-10 Interview
Population: 41 children missing race and ethnicity excluded; 1 child did not complete PedsQL
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Narrow Spectrum Antibiotic | Sleep Disturbance | 582 Participants |
| Broad Spectrum Antibiotic | Sleep Disturbance | 378 Participants |
Comparison: Propensity-score based full matching performed using patient and physician-level characteristics. Average treatment effect weights calculated and applied to a weighted logistic regression. Risk difference obtained by marginal standardization.p-value: 0.0795% CI: [-0.3, 9.6]Weighted logistic regression
Secondary
Symptoms Present on Day 3
During 5-10 day interview, parents were asked about symptoms related to child's illness (otitis media: fever, ear pain, decreased appetite; sinusitis: fever, face/head pain, decreased appetite; pharyngitis: throat pain, fever, decreased appetite). Parent was asked if symptoms was present at diagnosis. If yes, had the symptom resolved. If yes, when. We assessed whether symptoms present at day 3 after diagnosis.
Time frame: 3 days after ARTI diagnosis
Population: Among subjects who reported having at least one symptom at the time of diagnosis; 41 children missing race and ethnicity were excluded
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Narrow Spectrum Antibiotic | Symptoms Present on Day 3 | 427 Participants |
| Broad Spectrum Antibiotic | Symptoms Present on Day 3 | 267 Participants |
Comparison: Propensity-score based full matching performed using patient and physician-level characteristics. Average treatment effect weights calculated and applied to a weighted logistic regression. Risk difference obtained by marginal standardization.p-value: 0.0995% CI: [-0.8, 10.6]Weighted logistic regression