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. 2022 May 2;5(5):e2214153.
doi: 10.1001/jamanetworkopen.2022.14153.

Association of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events and Health Care Expenditures

Anne M Butler  1   2 , Derek S Brown  3 , Michael J Durkin  1 , John M Sahrmann  1 , Katelin B Nickel  1 , Caroline A O'Neil  1 , Margaret A Olsen  1   2 , David Y Hyun  4 , Rachel M Zetts  4 , Jason G Newland  5
Affiliations

Association of Inappropriate Outpatient Pediatric Antibiotic Prescriptions With Adverse Drug Events and Health Care Expenditures

Anne M Butler et al. JAMA Netw Open. .

Erratum in

  • Error in Figure 1.
    [No authors listed] [No authors listed] JAMA Netw Open. 2022 Jun 1;5(6):e2221479. doi: 10.1001/jamanetworkopen.2022.21479. JAMA Netw Open. 2022. PMID: 35713908 Free PMC article. No abstract available.

Abstract

Importance: Nonguideline antibiotic prescribing for the treatment of pediatric infections is common, but the consequences of inappropriate antibiotics are not well described.

Objective: To evaluate the comparative safety and health care expenditures of inappropriate vs appropriate oral antibiotic prescriptions for common outpatient pediatric infections.

Design, setting, and participants: This cohort study included children aged 6 months to 17 years diagnosed with a bacterial infection (suppurative otitis media [OM], pharyngitis, sinusitis) or viral infection (influenza, viral upper respiratory infection [URI], bronchiolitis, bronchitis, nonsuppurative OM) as an outpatient from April 1, 2016, to September 30, 2018, in the IBM MarketScan Commercial Database. Data were analyzed from August to November 2021.

Exposures: Inappropriate (ie, non-guideline-recommended) vs appropriate (ie, guideline-recommended) oral antibiotic agents dispensed from an outpatient pharmacy on the date of infection.

Main outcomes and measures: Propensity score-weighted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for the association between inappropriate antibiotic prescriptions and adverse drug events. Two-part models were used to calculate 30-day all-cause attributable health care expenditures by infection type. National-level annual attributable expenditures were calculated by scaling attributable expenditures in the study cohort to the national employer-sponsored insurance population.

Results: The cohort included 2 804 245 eligible children (52% male; median [IQR] age, 8 [4-12] years). Overall, 31% to 36% received inappropriate antibiotics for bacterial infections and 4% to 70% for viral infections. Inappropriate antibiotics were associated with increased risk of several adverse drug events, including Clostridioides difficile infection and severe allergic reaction among children treated with a nonrecommended antibiotic agent for a bacterial infection (among patients with suppurative OM, C. difficile infection: HR, 6.23; 95% CI, 2.24-17.32; allergic reaction: HR, 4.14; 95% CI, 2.48-6.92). Thirty-day attributable health care expenditures were generally higher among children who received inappropriate antibiotics, ranging from $21 to $56 for bacterial infections and from -$96 to $97 for viral infections. National annual attributable expenditure estimates were highest for suppurative OM ($25.3 million), pharyngitis ($21.3 million), and viral URI ($19.1 million).

Conclusions and relevance: In this cohort study of children with common infections treated in an outpatient setting, inappropriate antibiotic prescriptions were common and associated with increased risks of adverse drug events and higher attributable health care expenditures. These findings highlight the individual- and national-level consequences of inappropriate antibiotic prescribing and further support implementation of outpatient antibiotic stewardship programs.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Butler reported receiving investigator-initiated funds from Merck outside the submitted work. Dr Brown reported receiving investigator-initiated research funds from Pfizer outside the submitted work. Dr Durkin reported receiving grants from the National Institute of Dental and Craniofacial Research, the National Institute on Drug Abuse, and the US Centers for Disease Control and Prevention Epicenters and personal fees for serving as expert witness from Keating Jones and Stanton Barton outside the submitted work. Dr Olsen reported receiving grants and personal fees from Pfizer outside the submitted work. Dr Newland reported receiving investigator-initiated research funds from Merck. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Hazard Ratio (HR) Estimates of Adverse Drug Events Following Inappropriate vs Appropriate Antibiotic Prescriptions Among Pediatric Patients
Between 0.0% and 1.8% patients were excluded for 30-day safety outcomes (eTable 11 in the Supplement). Definitions of appropriate and inappropriate agents for bacterial and viral infections are provided in the Methods section. For HR estimation, at least 5 adverse event cases were required in both the reference category (ie, appropriate antibiotic prescription) and the comparator group (ie, inappropriate antibiotic prescription) to ensure stability of the effect estimate. Results for bacterial infections are denoted by a white background with blue boxes; viral infections, brown background with orange boxes. OM indicates otitis media; URI, upper respiratory infection.
Figure 2.
Figure 2.. Inverse Probability of Treatment–Weighted 30-Day Patient-Level Attributable Expenditure Estimates of Inappropriate Antibiotic Prescriptions Among Children by Infection Type
Black lines indicate 95% CIs. ADE indicates adverse drug event; OM, otitis media; and URI, upper respiratory infection.
See this image and copyright information in PMC

Comment in

References

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