Treatment Failure and Adverse Events After Amoxicillin-Clavulanate vs Amoxicillin for Pediatric Acute Sinusitis

Abstract

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.

Figure 1.. Screening and Patient Selection for Study of Amoxicillin-Clavulanate and Amoxicillin in Pediatric Sinusitis

Figure 2.. Treatment Failure After Propensity Score Matching

^aAmoxicillin-clavulanate indicates the exposure group, and amoxicillin indicates the referral group. ^bA new antibiotic could be any oral antibiotic except the index antibiotic dispensed on the cohort entry date. ^cSerious treatment failure indicates the first occurrence of (1) emergency department encounter for acute sinusitis; (2) inpatient encounter for acute sinusitis; and (3) inpatient encounter for sinusitis complications.

Figure 3.. Adverse Outcomes After Propensity Score Matching

^aAmoxicillin-clavulanate indicates the exposure group, and amoxicillin indicates the referral group. ^bMeasured from day 1 to day 14 after treatment initiation. ^cThe first occurrence of nausea/vomiting, abdominal pain, non–Clostridioides difficile diarrhea. ^dMeasured from day 1 to day 90 after treatment initiation. ^eIndicates the first occurrence of anaphylaxis, laryngeal edema, angioedema, unspecified allergy, and urticaria. Anaphylaxis, laryngeal edema, and angioedema were measured from day 0 to day 2 after treatment initiation, while unspecified allergy and urticaria were measured from day 1 to day 14 after treatment initiation.

Figure 4.. Treatment Failure and Adverse Outcomes Stratified by Age After Propensity Score Matching

^aAmoxicillin-clavulanate indicates the exposure group, and amoxicillin indicates the referral group. ^bThe sum of patients across strata does not equal the total number of patients in the primary analyses due to propensity score estimation and matching occurring after patients were stratified by age.