The Harms of Inappropriate Antibiotic Use in Kids

Children are often prescribed antibiotics inappropriately in the outpatient setting. The harms of this practice are poorly characterized but could inform risk-benefit discussions with parents.

In a cohort of 2.8 million commercially insured U.S. children (median age, 8 years-old), investigators noted inappropriate prescribing (e.g., antibiotic therapy for viral infections or nonfirst-line antibiotic therapy for bacterial infections) in approximately one third of bacterial infection cases and as many as 70% of viral infections (depending on the type of infection.)

  • Population: 6mo to 17yo children diagnosed in an outpatient setting with a common bacterial infection (suppurative OM, pharyngitis, sinusitis) or viral infection (influenza, viral URI, bronchiolitis, bronchitis, nonsuppurative OM)
  • Data source: IBM MarketScan Commercial Database (2015-2018), which contains longitudinal, patient-level data through insurance claims and their associated outpatient pharmacy-dispensed medications
  • Antibiotic exposure: An oral antibiotic prescription was linked to an outpatient infection if it occurred on the day of the index diagnosis. For bacterial infections, antibiotic prescriptions were labeled as appropriate (i.e., first-line agent) or inappropriate (i.e., nonfirst-line agent) based on treatment guidelines. For viral infections, antibiotic prescriptions were labeled as appropriate (i.e., not prescribed) or inappropriate (i.e., prescribed)
  • Safety outcomes: Adverse drug events (ADEs) were identified on medical claims during follow-up periods, which ranged from 2 days (hypersensitivity reactions), to 14 days (skin reactions, GI upset, kidney failure), to 90 days (C.difficile infection)

Hazard ratio (HR) is a measure of an effect of an intervention on an outcome of interest over time. Hazard ratio is reported most commonly in time-to-event analysis or survival analysis (i.e., when we are interested in knowing how long it takes for a particular event/outcome to occur.

HR = Hazard in the intervention group ÷ Hazard in the control group

Hazard represents the instantaneous event rate, which means the probability that an individual would experience an event (e.g., ADE) at a particular point in time after the intervention.

For bacterial infections, inappropriate prescribing was associated with 6x higher risk for Clostridium difficile infections, 4x higher risk for severe allergic reactions, and excess risk for diarrhea and other GI symptoms, compared with appropriate prescribing, within 90 days after the prescription. For viral infections, inappropriate prescribing was associated with excess risk for skin rash or urticaria.

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