The impact of topical or oral antibiotics in children with acute otitis media on their middle ear, nasopharyngeal, and gut microbiomes
Background. Acute otitis media (AOM) is a major driver of antibiotic prescriptions in children. Children presenting with AOM and ear discharge (AOMd) may be treated with oral amoxicillin and/or hydrocortisone-bacitracin-colistin eardrops. The impact of both treatment regimens on middle ear, nasopharynx and gut microbiome compositions, and the gut resistome, is uncertain. Methods. Fifty-eight children with AOMd presenting with ear pain and/or fever were randomised to either oral amoxicillin suspension (n=31) or hydrocortisone-bacitracin-colistin eardrops (n=27) for seven days. From 57 children (98%), baseline and Week-2 middle ear fluid (MEF) and nasopharyngeal (NP) samples were sequenced, along with baseline, Week-2, and Month-3 faecal samples.  Results.  Most baseline MEF samples – but not NP samples – were dominated by Streptococcus. The ear discharge was resolved by Week-2 in all but five children (oral suspension n=4, eardrops n=1). In those cases, Week-2 MEF samples were not dominated by Streptococcus but by Haemophilus or Staphylococcus, or contained mixed bacteria. Oral suspension reduced Streptococcus relative abundance and estimated concentrations in NP samples more effectively than eardrops (16.6% at baseline vs 4.8% oral and 10.1% eardrops at Week-2; ANCOM-BC p=0.001); but increased Moraxella and Haemophilus. Neither treatment significantly altered the faecal microbiome or resistome compositions at Week-2 and Month-3.  Conclusions. Oral amoxicillin suspension more effectively reduced Streptococcus in the NP, and likely also the middle ear, of children with AOMd than hydrocortisone-bacitracin-colistin eardrops. Future antibiotic trials should assess off-target microbiological effects, keeping in mind that NP samples are not a good proxy for the middle ear microbiome.