Inappropriate Antibiotics Prescribed to Pediatric Population Inconsistent with "First, do no Harm"

Inappropriate, off guideline antibiotic prescribing in pediatrics was linked to an eightfold increased risk of adverse drug events including C difficile infection, and greater health care costs, in a new study from Washington University in St Louis and the Pew Charitable Trusts.

Lead author, Anne Butler, PhD, and colleagues at Washington University, St Louis joined with David Hyun, MD and Rachel Zetts at the Pew Charitable Trusts to compare outcomes between inappropriate antibiotics and guideline-consistent prescribing in a cohort of more than 2.8 million children treated forcommon bacterial or viral infections in out-patient settings.

"Despite inappropriate antibiotic prescribing for the treatment of pediatric infections in the outpatient setting, evidence is limited on the risk related to inappropriate antibiotic prescriptions," Butler and colleagues observed.

In addition to differentiating outcomes and determining relative risks of individual adverse drug events, the investigators explained, "we also sought to estimate the national-level annual attributable expenditures of inappropriate antibiotic prescriptions..."

In a concurrently published overview of the study, the Pew Charitable Trusts also notes that antibiotic use drives development of antibiotic-resistant bacteria which cause more than 2.8 million infections and 35,000 deaths in the US each year.

"As a result, it is critical to improve antibiotic stewardship efforts, which help ensure that these drugs are prescribed appropriately," the statemen declares.

To distinguish outcomes between appropriate and inappropriate antibiotic prescribing in pediatric outpatients, the investigators accessed the IBM MarketScan Commercial Database from 2015-2018, identifying children 6 months to 17 years of age diagnosed in an outpatient setting with a common bacterial infection (suppurative otitis media (OM), pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection (URI), bronchiolitis in 6 months to 3 years of age, bronchitis in age 5-17 years, and nonsuppurative otitis media).

Antibiotic exposure corresponded to a prescription on the day of the index diagnosis. The investigators excluded index events with multiple oral antibiotic prescriptions or unusual treatment durations, as well as index events with other diagnoses for which antibiotics are warranted. Safety outcomes were derived from medical claims during subsequent 2 to 90 days. Health care costs were computed as the sum of out-of-pocket patient expenditures, and health plan expenditures.

Butler and colleagues found that antibiotics were inappropriately prescribed for 31-36% of bacterial infections and 4 to 70% for vial infections. Compared to appropriate prescribing, inappropriate antibiotics were associated with increased risk of several adverse events including C difficile infection (HR 6.23, 95% CI 2.24-17.32) and severe allergic reactions (HR 4.14, 2.48-6.92).

Attributable health care expenditures were generally higher with inappropriate antibiotics ($21-56 for bacterial infections; $96-97 for viral infections). They projected that national annual attributable expenditures were highest for suppurative OM ($25.3 million), pharyngitis ($21.3 million) and viral URI ($19.1 million).

In a press release from Washington University School of Medicine in St Louis, Butler reflected on their findings, and distinguishing between appropriate and inappropriate antibiotic prescribing.

"Sometimes parents think that the worst that could happen is that the antibiotic just won't help their child, But antibiotics are not harmless—they can cause adverse drug events," Butler commented. "Clinicians need to ensure that antibiotics are only used in the way that is most likely to benefit the patient."

In accompanying, invited commentary, Michael Smith, MD, MSCE, Duke Center for Antimicrobial Stewardship and Infection Prevention, Division of Pediatric Infectious Diseases, Department of Pediatrics Duke University Medical Center, Durham, NC, and Bethany Wattles, PharmD, MHA, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, emphasized the study findings that appropriate antibiotic prescribing reduces both complications and costs.

"This work identifies a clear opportunity to improve quality of care to children for common infections while also leading to significant cost savings. In the era of value-based care, this is a critical mission," Smith and Wattles assert.