Faculty Collaboration Database

Antibiotic modulation of mucins in otitis media; should this change our approach to watchful waiting? Int J Pediatr Otorhinolaryngol 2019 Oct;125:134-140

Date

07/16/2019

Pubmed ID

31302575

Pubmed Central ID

PMC6742428

DOI

10.1016/j.ijporl.2019.07.002

Scopus ID

2-s2.0-85068657202 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

BACKGROUND: Gel-forming mucins (GFMs) play important roles in otitis media (OM) pathogenesis. Increased mucin expression is activated by pathogens and proinflammatory cytokines. Bacterial biofilms influence inflammation and resolution of OM and may contribute to prolonged mucin production. The influence of specific pathogens on mucin expression and development of chronic OM with effusion (OME) remains an area of significant knowledge deficit.

OBJECTIVES: To assess the relationship between GFM expression, specific pathogens, middle ear mucosal (MEM) changes, biofilm formation, and antibiotic utilization.

METHODS: Mixed gender chinchillas were inoculated with nontypeable Haemophilus influenzae (NTHi) strain 86028NP or Streptococcus pneumoniae (SP) strain TIGR4 via transbulla injection. Antibiotic was administered on day 3-5 post inoculation. GFM expression was measured by quantitative PCR. Biofilm formation was identified and middle ear histologic changes were measured.

RESULTS: SP infection resulted in higher incidence of biofilm and ME effusion compared with NTHi infection. However, NTHi persisted in the ME longer than SP with no substantive bacterial clearance detected on day 10 compared with complete bacterial clearance on day 10 for 50-60% of the SP-infected chinchillas. Both infections increased MEM inflammatory cell infiltration and thickening. NTHi upregulated the Muc5AC, Muc5B and Muc19 expression on day 10 (p = 0.0004, 0.003, and 0.002 respectively). SP-induced GFM upregulations were trended toward significant. In both NTHi and SP infections, the degree of GFM upregulation had a direct relationship to increased MEM hypertrophy, inflammatory cell infiltration and biofilm formation. Antibiotic treatment reduced the incidence of ME effusion and biofilm, limited the MEM changes and reversed the GFM upregulation. In NTHi infection, the rate of returning to baseline level of GFMs in treated chinchillas was quicker than those without treatment.

CONCLUSIONS: In an animal model of OM, GFM genes are upregulated in conjunction with MEM hypertrophy and biofilm formation. This upregulation is less robust and more quickly ameliorated to a significant degree in the NTHi infection with appropriate antibiotic therapy. These findings contribute to the understanding of pathogen specific influences on mucin expression during OM pathogenesis and provide new data which may have implications in clinical approach for OM treatment.

Author List

Hong W, Khampang P, Kerschner AR, Mackinnon AC, Yan K, Simpson PM, Kerschner JE

Authors

Wenzhou Hong DVM, PhD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
Ke Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Bacterial Agents
Biofilms
Chinchilla
Disease Models, Animal
Haemophilus Infections
Haemophilus influenzae
Mucin 5AC
Mucin-5B
Otitis Media
Pneumococcal Infections
Streptococcus pneumoniae
Up-Regulation
Watchful Waiting