Treatment Failure and Adverse Events After Amoxicillin-Clavulanate vs Amoxicillin for Pediatric Acute Sinusitis
Timothy J Savage1,2,3, Matthew P Kronman4, Sushama Kattinakere Sreedhara1
1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Insights
Amoxicillin-clavulanate and amoxicillin show similar treatment success for childhood acute sinusitis. However, amoxicillin-clavulanate increases risks of gastrointestinal issues and yeast infections in pediatric patients.
Area of Science:
- Pediatric infectious diseases
- Clinical pharmacology
- Evidence-based medicine
Background:
- Acute sinusitis is a frequent reason for antibiotic prescriptions in children.
- Optimal empirical antibiotic selection for acute sinusitis lacks consensus.
Purpose of the Study:
- To compare the efficacy and safety of amoxicillin-clavulanate versus amoxicillin for treating acute sinusitis in outpatient children.
Main Methods:
- A retrospective cohort study utilized a nationwide healthcare database.
- Children and adolescents (≤17 years) diagnosed with acute sinusitis were included.
- Propensity score matching was employed to control for confounding factors.
Main Results:
- No significant difference in treatment failure rates was observed between amoxicillin-clavulanate and amoxicillin.
- Amoxicillin-clavulanate was associated with increased risks of gastrointestinal symptoms and yeast infections.
- Age-stratified analysis indicated no difference in treatment failure, but higher adverse event risks with amoxicillin-clavulanate in younger children.
Conclusions:
- For outpatient pediatric acute sinusitis, amoxicillin-clavulanate offers no superior treatment failure rate compared to amoxicillin.
- Amoxicillin-clavulanate use in children is linked to a higher incidence of gastrointestinal distress and secondary yeast infections.
- Findings support informed antibiotic selection for acute sinusitis, considering both efficacy and potential adverse events.
Importance:
Acute sinusitis is one of the most common indications for antibiotic prescribing in children, with an estimated 4.9 million such prescriptions in the US annually. Consensus does not exist regarding the optimal empirical antibiotic.
Objective:
To compare amoxicillin-clavulanate vs amoxicillin for the treatment of acute sinusitis in outpatient children.
Design, Setting, And Participants:
Cohort study of children and adolescents aged 17 years or younger with a new outpatient diagnosis of acute sinusitis and a same-day new prescription dispensation of amoxicillin-clavulanate or amoxicillin in a nationwide health care utilization database. Propensity score matching was used to mitigate confounding.
Exposure:
A new prescription dispensation of amoxicillin-clavulanate or amoxicillin.
Main Outcomes And Measures:
Treatment failure, defined as an aggregate of a new antibiotic dispensation, emergency department or inpatient encounter for acute sinusitis, or inpatient encounter for a sinusitis complication, was assessed 1 to 14 days after cohort enrollment. Adverse events were evaluated, including gastrointestinal symptoms, hypersensitivity and skin reactions, acute kidney injury, and secondary infections.
Results:
The cohort included 320 141 patients. After propensity score matching, there were 198 942 patients (99 471 patients per group), including 100 340 (50.4%) who were female, 101 726 (51.1%) adolescents aged 12 to 17 years, 52 149 (26.2%) children aged 6 to 11 years, and 45 067 (22.7%) children aged 0 to 5 years. Treatment failure occurred in 1.7% overall; 0.01% had serious failure (an emergency department or inpatient encounter). There was no difference in the risk of treatment failure between the amoxicillin-clavulanate and amoxicillin groups (relative risk [RR], 0.98 [95% CI, 0.92-1.05]). The risk of gastrointestinal symptoms (RR, 1.15 [95% CI, 1.05-1.25]) and yeast infections (RR, 1.33 [95% CI, 1.16-1.54]) was higher with amoxicillin-clavulanate. After patients were stratified by age, the risk of treatment failure after amoxicillin-clavulanate was an RR of 0.98 (95% CI, 0.86-1.12) for ages 0 to 5 years; RR was 1.06 (95% CI, 0.92-1.21) for 6 to 11 years; and RR was 0.87 (95% CI, 0.79-0.95) for 12 to 17 years. The age-stratified risk of adverse events after amoxicillin-clavulanate was an RR of 1.23 (95% CI, 1.10-1.37) for ages 0 to 5 years; RR was 1.19 (95% CI, 1.04-1.35) for 6 to 11 years; and RR was 1.04 (95% CI, 0.95-1.14) for 12 to 17 years.
Conclusions And Relevance:
In children with acute sinusitis who were treated as outpatients, there was no difference in the risk of treatment failure between those who received amoxicillin-clavulanate compared with amoxicillin, but amoxicillin-clavulanate was associated with a higher risk of gastrointestinal symptoms and yeast infections. These findings may help inform decisions for empirical antibiotic selection in acute sinusitis.
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