Oral and middle ear delivery of otitis media standard of care antibiotics, but not biofilm-targeted antibodies, alter chinchilla nasopharyngeal and fecal microbiomes

• Published in: NPJ biofilms and microbiomes 2024-02, Vol.10 (1), p.10-10, Article 10
• Main Authors: Duff, Audrey F., Jurcisek, Joseph A., Kurbatfinski, Nikola, Chiang, Tendy, Goodman, Steven D., Bakaletz, Lauren O., Bailey, Michael T.
• Format: Article
• Language: English
• Subjects: 631/326/2565/2134; 692/698/2741/2135; Amoxicillin; Animals; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antibodies; Antimicrobial resistance; Biofilms; Biomedical and Life Sciences; Child; Chinchilla; Dysbacteriosis; Ear diseases; Ear, Middle - pathology; Epitopes; Feces; Humans; Integration host factor; Life Sciences; Medical Microbiology; Microbial Ecology; Microbial Genetics and Genomics; Microbiology; Microbiomes; Middle ear; Monoclonal antibodies; Nasopharynx; Nasopharynx - pathology; Ofloxacin; Opportunist infection; Otitis media; Otitis Media - drug therapy; Pathogens; Pediatrics; PilA protein; Secondary infection; Standard of Care; Structural proteins; Sulfamethoxazole; Trimethoprim; Trimethoprim-sulfamethoxazole
• ISSN: 2055-5008; 2055-5008
• DOI: 10.1038/s41522-024-00481-0

Otitis media (OM) is one of the most globally pervasive pediatric conditions. Translocation of nasopharynx-resident opportunistic pathogens like nontypeable Haemophilus influenzae (NTHi) assimilates into polymicrobial middle ear biofilms, which promote OM pathogenesis and substantially diminish antibiotic efficacy. Oral or tympanostomy tube (TT)-delivered antibiotics remain the standard of care (SOC) despite consequences including secondary infection, dysbiosis, and antimicrobial resistance. Monoclonal antibodies (mAb) against two biofilm-associated structural proteins, NTHi-specific type IV pilus PilA (anti-rsPilA) and protective tip-region epitopes of NTHi integration host factor (anti-tip-chimer), were previously shown to disrupt biofilms and restore antibiotic sensitivity in vitro. However, the additional criterion for clinical relevance includes the absence of consequential microbiome alterations. Here, nine chinchilla cohorts ( n  = 3/cohort) without disease were established to evaluate whether TT delivery of mAbs disrupted nasopharyngeal or fecal microbiomes relative to SOC-OM antibiotics. Cohort treatments included a 7d regimen of oral amoxicillin-clavulanate (AC) or 2d regimen of TT-delivered mAb, AC, Trimethoprim-sulfamethoxazole (TS), ofloxacin, or saline. Fecal and nasopharyngeal lavage (NPL) samples were collected before and several days post treatment (DPT) for 16S sequencing. While antibiotic-treated cohorts displayed beta-diversity shifts (PERMANOVA, P