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

Phase 4
Completed
Conditions
Acute Otitis Media
Interventions
Drug: Amoxicillin-Potassium Clavulanate
Drug: Macrolide
Registration Number
NCT02935374
Lead Sponsor
University of Oulu
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
73
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Amoxicillin-Potassium ClavulanateAmoxicillin-Potassium ClavulanateThe 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.
MacrolideMacrolideThe 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.
AmoxicillinAmoxicillinThe children with acute otitis media will be treated with amoxicillin mixture, 100mg/ml, 40mg/kg/d, divided to two daily doses for 7 days.
Primary Outcome Measures
NameTimeMethod
Change in the relative abundance of Firmicutes in stool samplesChange 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 Outcome Measures
NameTimeMethod
Change in the relative abundance of Actinobacteria in stool samplesChange 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 Faecalibacterium prausnitzii in stool samplesChange 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)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

Principal coordinate analysis (PCA) of fecal samples10 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 Lactobacilli in stool samplesChange 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 Bacteroidetes in stool samplesChange 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 samplesChange 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 samplesChange 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 Bifidobacteria in stool samplesChange 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 diversity of fecal microbiota measured with Shannon indexChange 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 indexChange 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 metagenomics10 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 samples10 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 strains10 days

Proportion of fecal samples with Extended Spectrum Beta-Lactamase -positive strains 10 days after the diagnosis of acute otitis media

Trial Locations

Locations (1)

Mehiläinen, private practice

🇫🇮

Oulu, Finland

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