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

Effect of Antimicrobial Treatment of Acute Otitis Media on the Intestinal Microbiome in Children: A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Acute Otitis Media
• Intervention / Treatment: Drug: Amoxicillin; Drug: Amoxicillin-Potassium Clavulanate; Drug: Macrolide

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.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 4

Contacts and Locations

Study Locations

• Finland
  • Oulu, Finland
    • Mehiläinen, private practice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.
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.	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.
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.	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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Oulu
• Collaborators: Oulu University Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: September 28, 2016
• First Submitted That Met QC Criteria: October 12, 2016
• First Posted (Estimate): October 17, 2016

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: children; microbiota; amoxicillin; intestinal microbiome; macrolide; amoxicillin-clavulanate; antimicrobial course
• Additional Relevant MeSH Terms: Otorhinolaryngologic Diseases; Ear Diseases; Otitis; Otitis Media; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids
• Other Study ID Numbers: OY20167

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No