Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children

Overview

This is a randomized, controlled trial studying the effects of various antimicrobial treatments on the intestinal microbiome of small children. The participating children with acute otitis media are treated wither with amoxicillin, amoxicillin-clavulanate or without antibiotics. The children with allergy to amoxicillin receive a course of macrolide and they will be monitored as a separate group. The main outcomes of this trial are the changes in the intestinal microbiome after the treatment.

Full Title of Study: “Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children: A Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: March 2020

Detailed Description

Antimicrobial treatment of acute otitis media has been proven efficacious in children. It has been suggested that antimicrobial treatment makes a lot of harm to intestinal microbiome and may thus have effects on the child's health and wellbeing. However, data on these changes and their magnitude is scanty. This is a randomized, controlled trial studying the effects of various antimicrobial treatments on the intestinal microbiome of small children. The participating children with acute otitis media are treated wither with amoxicillin, amoxicillin-clavulanate or without antibiotics. The children with allergy to amoxicillin receive a course of macrolide and they will be monitored as a separate group. The main outcomes of this trial are the changes in the intestinal microbiome after the treatment.

Interventions

  • Drug: Amoxicillin
    • The children with acute otitis media will be treated with amoxixillin mixture, 100mg/ml, 40mg/kg/d, divided to two daily doses for 7 days.
  • Drug: Amoxicillin-Potassium Clavulanate
    • The children with acute otitis media will be treated with amoxixillin-clavulanate mixture, 80mg/ml, 45mg/kg/d, divided to two daily doses for 7 days.
  • Drug: Macrolide
    • The children with acute otitis media with a know allergy to amoxicillin or amoxicillin-clavulanate will be treated with macrolide and monitored separately

Arms, Groups and Cohorts

  • Active Comparator: Amoxicillin
    • The children with acute otitis media will be treated with amoxicillin mixture, 100mg/ml, 40mg/kg/d, divided to two daily doses for 7 days.
  • Active Comparator: Amoxicillin-Potassium Clavulanate
    • The children with acute otitis media will be treated with amoxicillin-clavulanate mixture, 80mg/ml, 45mg/kg/d, divided to two daily doses for 7 days.
  • No Intervention: Wait and see
    • The children with acute otitis media will be monitored without antimicrobial treatment.
  • Other: Macrolide
    • The children with acute otitis media with known allergy to amoxicillin or amoxicillin-clavulanate will be treated with macrolide and monitored as a separate group, outside randomization.

Clinical Trial Outcome Measures

Primary Measures

  • Change in the relative abundance of Firmicutes in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Firmicutes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.

Secondary Measures

  • Principal coordinate analysis (PCA) of fecal samples
    • Time Frame: 10 days
    • Principal coordinate analysis (PCA) of the microbiota of fecal samples 10 days after starting treatment to acute otitis media
  • Change in the relative abundance of Actinobacteria in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Actinobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the relative abundance of Bacteroidetes in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Bacteroidetes in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the relative abundance of Proteobacteria in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Proteobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the relative abundance of Verrucomicrobia in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Verrucomicrobia in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the relative abundance of Lactobacilli in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Lactobacilli in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the relative abundance of Bifidobacteria in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Bifidobacteria in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the relative abundance of Faecalibacterium prausnitzii in stool samples
    • Time Frame: Change from baseline to 10 days
    • Change in the relative abundance of Faecalibacterium prausnitzii in stool samples obtained at baseline and at 10 days after the diagnosis of acute otitis media.
  • Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs)
    • Time Frame: Change from baseline to 10 days
    • Change in the diversity of fecal microbiota measured with the number of operational taxonomic units (OTUs) from baseline to 10 days after the diagnosis of acute otitis media
  • Change in the diversity of fecal microbiota measured with Shannon index
    • Time Frame: Change from baseline to 10 days
    • Change in the diversity of fecal microbiota measured with Shannon index from baseline to 10 days after the diagnosis of acute otitis media
  • Change in the diversity of fecal microbiota measured with Chao index
    • Time Frame: Change from baseline to 10 days
    • Change in the diversity of fecal microbiota measured with Chao index from baseline to 10 days after the diagnosis of acute otitis media
  • Presence of antimicrobial genes measured with the means of metagenomics
    • Time Frame: 10 days
    • Presence of antimicrobial genes measured with the means of metagenomics at 10 days after the diagnosis of acute otitis media
  • Proportion of Clostridium difficile -positive fecal samples
    • Time Frame: 10 days
    • Occurrence of Clostridium difficile in fecal samples 10 days after the diagnosis of acute otitis media
  • Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains
    • Time Frame: 10 days
    • Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains 10 days after the diagnosis of acute otitis media

Participating in This Clinical Trial

Inclusion Criteria

  • acute symptoms of respiratory infection AND – signs of inflammation on the tympanic membrane in otoscopy AND – middle ear effusion found in pneumatic otoscopy Exclusion Criteria:

  • Suspected or proven complication of acute otitis media (for example acute mastoiditis or perforated tympanic membrane) – Severe acute otitis media: severe pain and fever > 39 degrees C – Bilateral acute otitis media in a child younger than 2 years – Primary or secondary immunodeficiency or Downs syndrome – Impaired general condition or suspected severe bacterial infection – Allergy to both amoxicillin and macrolide – Acute otorrhea through tympanostomy tube – Antimicrobial treatment ongoing or during previous 7 days

Gender Eligibility: All

Minimum Age: 6 Months

Maximum Age: 7 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Oulu
  • Collaborator
    • Oulu University Hospital
  • Provider of Information About this Clinical Study
    • Sponsor

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