Article Identification

• Article Title: Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children
• Citation: Alejandro Hoberman, Jack L. Paradise, Howard E. Rockette, et al. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. The New England Journal of Medicine. 2016;375(25):2446-2456.
• DOI: 10.1056/NEJMoa1606043

Quick Reference Summary

• A 5-day course of amoxicillin-clavulanate in children aged 6–23 months with acute otitis media resulted in a significantly higher clinical failure rate (34%) compared to the standard 10-day regimen (16%), exceeding the predefined noninferiority margin (difference: 17 percentage points, 95% CI: 9–25).
• No significant differences were observed between the two treatment durations in recurrence rates, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens.

Core Clinical Question

Does a 5-day course of amoxicillin-clavulanate result in noninferior clinical outcomes compared to a standard 10-day course in treating acute otitis media in children aged 6 to 23 months?

Background

• Disease Overview:
  • Acute otitis media (AOM) is the second most frequently diagnosed illness in children in the United States and the most common reason for antimicrobial prescriptions.
• Prior Data:
  • Two trials supported routine antimicrobial treatment in children under 3 years, showing better outcomes with 7 or 10-day antibiotic courses compared to placebo (Hoberman et al., 2011; Tähtinen et al., 2011).
  • Previous studies comparing reduced-duration (e.g., 5-day) with standard-duration treatments have shown either no difference or modest superiority of longer courses, but with methodological limitations (Kozyrskyj et al., 2010; Dagan & McCracken, 2002).
• Current Standard of Care:
  • Typically involves a 10-day course of amoxicillin-clavulanate for treating AOM in young children to ensure efficacy and reduce recurrence.
• Knowledge Gaps Addressed by the Study:
  • Whether a shortened 5-day antibiotic course is noninferior to the standard 10-day treatment regarding clinical outcomes.
• Study Rationale:
  • To explore alternative treatment durations that could potentially reduce antimicrobial resistance without compromising clinical efficacy in treating AOM.

Methods Summary

• Study Design: Randomized, double-blind, noninferiority controlled trial.
• Setting/Time Period: Conducted from January 2012 through September 2015 at Children’s Hospital of Pittsburgh, affiliated pediatric practices, and Kentucky Pediatric and Adult Research in Bardstown, Kentucky.
• Population Characteristics: 520 children aged 6 to 23 months diagnosed with acute otitis media.
• Inclusion/Exclusion Criteria: Included children who had received at least two doses of pneumococcal conjugate vaccine and met specific symptomatic and otoscopic criteria. Excluded were children with tympanic-membrane perforation, allergic to amoxicillin, or who had received more than one antibacterial dose within the preceding 96 hours.
• Intervention Details:
  • Standard Duration Group: Received amoxicillin-clavulanate for 10 days (90 mg amoxicillin/kg and 6.4 mg clavulanate/kg per day).
  • Reduced Duration Group: Received amoxicillin-clavulanate for 5 days followed by placebo for the remaining 5 days.
• Control/Comparison Group Details: The standard 10-day antibiotic regimen served as the control.
• Outcomes:
  • Primary Outcome: Percentage of children experiencing clinical failure by the end of treatment.

Detailed Results

• Participant Flow and Demographics:
  • Enrollment: Out of 1,569 screened children, 896 were eligible, and 520 were randomized (257 to the 10-day group and 258 to the 5-day group).
  • Completion Rates: End-of-treatment assessments were completed for 93% of the 10-day group and 89% of the 5-day group.
  • Baseline Characteristics: No significant differences between groups regarding age, sex, exposure to other children, AOM-SOS scores, or severity of illness.
• Primary Outcome Results:
  • Clinical Failure: 34% (77/229) in the 5-day group vs. 16% (39/238) in the 10-day group; difference of 17 percentage points (95% CI: 9–25; P < 0.001).
  • Noninferiority Criterion: Not met, as the upper bound of the confidence interval exceeded the 10 percentage point margin.

Authors' Conclusions

• Among children aged 6 to 23 months with acute otitis media, a reduced-duration antimicrobial regimen of amoxicillin-clavulanate for 5 days resulted in significantly higher rates of clinical failure compared to the standard 10-day treatment.

Critical Analysis

A. Strengths

• Methodological Rigor: The study employed a randomized, double-blind, placebo-controlled design with a robust noninferiority framework, enhancing internal validity.

Literature Review

• Comparison with Supporting Trials:
  • Hoberman et al. (2016): Compared to prior findings showing the efficacy of standard duration versus placebo.

Clinical Application

• Suggests that a standard 10-day course of amoxicillin-clavulanate remains the preferred treatment duration for acute otitis media in children aged 6 to 23 months to minimize clinical failures.

How To Use This Info In Practice

Clinicians should adhere to the standard 10-day antibiotic regimen for acute otitis media in young children to ensure optimal clinical outcomes.