The risks associated with the inappropriate use of antibiotics include the occurrence of ADEs and increased healthcare expenditures; however, evidence is limited in the outpatient setting on the potential for ADEs, especially among children.

Researchers conducted a cohort study to evaluate the comparative safety and national-level annual attributable healthcare expenditures associated with inappropriate outpatient antibiotic prescriptions for children with commercial insurance who had several common bacterial and viral infections.

Using data from the IBM MarketScan Commercial Database from 2015 to 2018, researchers identified children aged 6 months to 17 years who had patient-level data, including adjudicated inpatient and outpatient insurance claims and outpatient pharmacy–dispensed medication claims data. To be included in the study, pediatric patients had to have an outpatient diagnosis of a common bacterial infection (i.e., suppurative otitis media [OM], pharyngitis, sinusitis) or a virus infection (i.e., influenza, viral upper respiratory tract infection [URI], bronchiolitis in those aged 6 months-3 years, bronchitis in those aged 5-17 years, and nonsuppurative OM) between April 1, 2016, and September 30, 2018. To be enrolled, children also had to have continuous health insurance enrollment and prescription drug coverage during the 180-day baseline period before the index date, which was defined as the date of diagnosis.

Patients were excluded if they had undergone an inpatient or skilled nursing facility admission within 90 days before the index date; received hospice or were on mechanical ventilation within 180 days before the index date; had serious underlying medical conditions within 180 days before the index date; had a previous diagnosis for the condition of interest within 180 days prior to the index date; used an antibiotic within 90 days before the index date; were dispensed multiple oral antibiotic prescriptions or had prescriptions with unusual treatment duration (i.e., too short [less than 5 days] or too long [more than 14 days]); and had index events for other diagnoses for which antibiotics were warranted.

Index events with other diagnoses for which antibiotics are warranted, bacterial and viral infection index events on the same day, and viral infection index events simultaneously coded for bacterial processes (i.e., suppurative OM, sinusitis, or pharyngitis) were also excluded. Use of antibiotic eardrop with a diagnosis of nonsuppurative OM was excluded in the expenditure analyses. Only the first qualifying event per diagnosis per child was considered.

An oral prescription was linked to an outpatient infection if it occurred on the day of the index diagnosis. The 2016 antibiotic utilization quality measure in the Healthcare Effectiveness Data and Information Set was used to define 36 index oral antibiotics. First-line antibiotics included amoxicillin for suppurative OM; amoxicillin or penicillin for pharyngitis; and amoxicillin or amoxicillin-clavulanate for sinusitis. No antibiotics were deemed appropriate for viral infections.

Safety was assessed using the International Classification of Disease (ICD)-10 diagnosis codes for ADEs. Children diagnosed with the outcome of interest 30 days before the index for each ADE were excluded. Clostridioides difficile infection was only assessed in children aged 2 to 17 years.

Healthcare expenditures included the sum of out-of-pocket expenditures such as copayments, coinsurance, deductions, and health plan expenditures. Both all-cause healthcare expenditures and antibiotic ADE-associated healthcare expenditures were determined.

Tendinopathy was used as a negative control as it is not treated with antibiotics.

Children who made up the total sample had a mean age of 8 years. The total sample size consisted of 1,601,019 bacterial infections, of which 38% were suppurative OM, 39% were pharyngitis, and 24% were due to sinusitis. There were 1,203,226 viral infections consisting of influenza (15%), viral URI (64%), bronchiolitis (2%), bronchitis (6%), and nonsuppurative OM (13%).

Of the bacterial infections, the following percentages were inappropriately treated: sinusitis (36%), pharyngitis (34%), and suppurative OM (31%). Among the viral infections whose diagnoses were inappropriately treated were bronchitis (70%), nonsuppurative OM (48%), viral URIs (12%), bronchiolitis (9%), and influenza (4%).

Inappropriate antibiotic use was associated with a 6.23-fold increased risk of C difficile infection, a 1.3-fold elevated risk of non–C difficile diarrhea, and a 1.20-fold increased risk of nausea, vomiting, or abdominal pain in children with suppurative OM.

There was a 38% lower risk of skin rash or urticaria and a 33% decrease in unspecified allergy in children with suppurative OM. When antibiotics were given inappropriately for viral infections, there was increased rate of skin rash, urticaria, and unspecified allergy.

For bacterial infections, the mean total attributable expenditure of inappropriate antibiotic use ranged from a low cost of $21 for sinusitis, to a medium expense of $42 for pharyngitis, and a high cost of $56 for suppurative OM. For viral infections, the mean total attributable expenditure associated with unnecessary antibiotics was $97 for influenza and $81 for a viral URI. Based on these numbers, it was projected that the national annual expenditure for inappropriately prescribed antibiotics for pediatric patients with commercial insurance was $25.3 million for suppurative OM, $21.3 million for pharyngitis, and $19.1 million on viral upper respiratory tract infections.

This study is a wake-up call that speaks to the need for antibiotic stewardship in the outpatient setting. Pharmacists are the healthcare professional most accessible and capable in responding to this call.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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