Targeting host-microbial interactions to develop otitis media therapies
Lea-Ann S Kirkham A B C and Ruth B Thornton A B
+ Author Affiliations
- Author Affiliations
A Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia
B Centre for Child Health Research, The University of Western Australia, Perth, WA, Australia
C Email: Lea-Ann.Kirkham@telethonkids.org.au
Microbiology Australia 42(2) 75-78 https://doi.org/10.1071/MA21019
Submitted: 18 March 2021 Accepted: 1 April 2021 Published: 20 May 2021
Journal Compilation © The Authors 2021 Open Access CC BY-NC-ND, published (by CSIRO Publishing) on behalf of the ASM
Abstract
Otitis media (OM; middle ear infection) is the most common reason for pre-school children to visit a doctor, be prescribed antimicrobials, or undergo surgery. Recent Cochrane reviews of clinical trials have identified that antibiotics and grommet surgery are only moderately effective in treating OM, with recurrent or persistent infection observed in one-third of children. Research efforts are focusing on developing improved therapies to treat OM and prevent disease recurrence. The recurrent nature of OM is mostly due to the persistence of bacterial pathogens within established biofilm in the middle ear. Promising novel therapies are harnessing host-microbe interactions to disrupt middle ear biofilm and permit antibiotics to work more effectively. New approaches are also being developed to prevent OM, including new vaccines and mining the host respiratory microbiome to develop novel bacterial therapies. This review describes how our improved knowledge of human and microbial interactions is driving development of OM therapies to improve health outcomes for children in Australia and worldwide.
References
[1] Monasta, L. et al. (2012) Burden of disease caused by otitis media: systematic review and global estimates. PLoS One 7, e36226.| Burden of disease caused by otitis media: systematic review and global estimates.Crossref | GoogleScholarGoogle Scholar | 23118930PubMed |
[2] Australian Institute of Health and Welfare (AIHW) (2018) Australia’s Health 2018.
[3] Homøe, P. et al. (2020) Panel 5: Impact of otitis media on quality of life and development. Int. J. Pediatr. Otorhinolaryngol. 130, 109837.
| Panel 5: Impact of otitis media on quality of life and development.Crossref | GoogleScholarGoogle Scholar | 32057518PubMed |
[4] Massa, H.M. et al. (2009) Otitis media: viruses, bacteria, biofilms and vaccines. Med. J. Aust. 191, S44–S49.
| Otitis media: viruses, bacteria, biofilms and vaccines.Crossref | GoogleScholarGoogle Scholar | 19883356PubMed |
[5] Ngo, C.C. et al. (2016) Predominant bacteria detected from the middle ear fluid of children experiencing otitis media: a systematic review. PLoS One 11, e0150949.
| Predominant bacteria detected from the middle ear fluid of children experiencing otitis media: a systematic review.Crossref | GoogleScholarGoogle Scholar | 26953891PubMed |
[6] Thornton, R.B. et al. (2013) Neutrophil extracellular traps and bacterial biofilms in middle ear effusion of children with recurrent acute otitis media--a potential treatment target. PLoS One 8, e53837.
| Neutrophil extracellular traps and bacterial biofilms in middle ear effusion of children with recurrent acute otitis media--a potential treatment target.Crossref | GoogleScholarGoogle Scholar | 23393551PubMed |
[7] Thornton, R.B. et al. (2011) Multi-species bacterial biofilm and intracellular infection in otitis media. BMC Pediatr. 11, 94.
| Multi-species bacterial biofilm and intracellular infection in otitis media.Crossref | GoogleScholarGoogle Scholar | 22018357PubMed |
[8] Bakaletz, L.O. (2012) Bacterial biofilms in the upper airway – evidence for role in pathology and implications for treatment of otitis media. Paediatr. Respir. Rev. 13, 154–159.
| Bacterial biofilms in the upper airway – evidence for role in pathology and implications for treatment of otitis media.Crossref | GoogleScholarGoogle Scholar | 22726871PubMed |
[9] Seppanen, E.J. et al. (2020) Bacterial reservoirs in the middle ear of otitis-prone children are associated with repeat ventilation tube insertion. Pediatr. Infect. Dis. J. 39, 91–96.
| Bacterial reservoirs in the middle ear of otitis-prone children are associated with repeat ventilation tube insertion.Crossref | GoogleScholarGoogle Scholar | 31725550PubMed |
[10] Venekamp, R.P. et al. (2016) Antibiotics for otitis media with effusion in children. Cochrane Database Syst. Rev. , CD009163.
| Antibiotics for otitis media with effusion in children.Crossref | GoogleScholarGoogle Scholar | 27977844PubMed |
[11] Leach, A.J. and Morris, P.S. (2006) Antibiotics for the prevention of acute and chronic suppurative otitis media in children. Cochrane Database Syst. Rev. , CD004401.
| Antibiotics for the prevention of acute and chronic suppurative otitis media in children.Crossref | GoogleScholarGoogle Scholar | 17054203PubMed |
[12] Venekamp, R.P. et al. (2018) Grommets (ventilation tubes) for recurrent acute otitis media in children. Cochrane Database Syst. Rev. , CD012017.
| Grommets (ventilation tubes) for recurrent acute otitis media in children.Crossref | GoogleScholarGoogle Scholar | 29741289PubMed |
[13] Schilder, A.G. et al. (2017) Panel 7: otitis media: treatment and complications. Otolaryngol. Head Neck Surg. 156, S88–S105.
| Panel 7: otitis media: treatment and complications.Crossref | GoogleScholarGoogle Scholar | 28372534PubMed |
[14] Alderson, M.R. et al. (2020) Panel 8: vaccines and immunology. Int. J. Pediatr. Otorhinolaryngol. 130, 109839.
| 31948716PubMed |
[15] Scott, A.M. et al. (2019) Probiotics for preventing acute otitis media in children. Cochrane Database Syst. Rev. , CD012941.
| Probiotics for preventing acute otitis media in children.Crossref | GoogleScholarGoogle Scholar | 31210358PubMed |
[16] Edmunds, A.L. (2017) Otiprio: an FDA-approved ciprofloxacin suspension gel for pediatric otitis media with effusion. P&T 42, 307–311.
[17] Bakaletz, L.O. (2007) Bacterial biofilms in otitis media: evidence and relevance. Pediatr. Infect. Dis. J. 26, S17–S19.
| Bacterial biofilms in otitis media: evidence and relevance.Crossref | GoogleScholarGoogle Scholar | 18049376PubMed |
[18] Novotny, L.A. et al. (2015) Antibodies against the majority subunit of type IV pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media. Mol. Microbiol. 96, 276–292.
| Antibodies against the majority subunit of type IV pili disperse nontypeable Haemophilus influenzae biofilms in a LuxS-dependent manner and confer therapeutic resolution of experimental otitis media.Crossref | GoogleScholarGoogle Scholar | 25597921PubMed |
[19] Mokrzan, E.M. et al. (2020) Nontypeable Haemophilus influenzae newly released (NRel) from biofilms by antibody-mediated dispersal versus antibody-mediated disruption are phenotypically distinct. Biofilm. 2, 100039.
| Nontypeable Haemophilus influenzae newly released (NRel) from biofilms by antibody-mediated dispersal versus antibody-mediated disruption are phenotypically distinct.Crossref | GoogleScholarGoogle Scholar | 33447823PubMed |
[20] Wilkinson, T.M.A. et al. (2019) Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: a phase 2 clinical trial. Vaccine 37, 6102–6111.
| Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: a phase 2 clinical trial.Crossref | GoogleScholarGoogle Scholar |
[21] Novotny, L.A. et al. (2021) Humanized anti-DNABII fab fragments plus ofloxacin eradicated biofilms in experimental otitis media. Laryngoscope. , .
| Humanized anti-DNABII fab fragments plus ofloxacin eradicated biofilms in experimental otitis media.Crossref | GoogleScholarGoogle Scholar | 33666254PubMed |
[22] Novotny, L.A. et al. (2017) Transcutaneous immunization with a band-aid prevents experimental otitis media in a polymicrobial model. Clin. Vaccine Immunol. 24, e00563-16.
| Transcutaneous immunization with a band-aid prevents experimental otitis media in a polymicrobial model.Crossref | GoogleScholarGoogle Scholar | 28381402PubMed |
[23] Man, W.H. et al. (2017) The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat. Rev. Microbiol. 15, 259–270.
| The microbiota of the respiratory tract: gatekeeper to respiratory health.Crossref | GoogleScholarGoogle Scholar | 28316330PubMed |
[24] Marsh, R.L. et al. (2020) Panel 4: Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures. Int. J. Pediatr. Otorhinolaryngol. 130, 109836.
| Panel 4: Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures.Crossref | GoogleScholarGoogle Scholar | 31879084PubMed |
[25] Pickering, J.L. et al. (2016) Haemophilus haemolyticus interaction with host cells is different to nontypeable Haemophilus influenzae and prevents NTHi association with epithelial cells. Front. Cell. Infect. Microbiol. 6, 50.
| Haemophilus haemolyticus interaction with host cells is different to nontypeable Haemophilus influenzae and prevents NTHi association with epithelial cells.Crossref | GoogleScholarGoogle Scholar | 27242968PubMed |
[26] Granland, C.M. et al. (2020) Nasal delivery of a commensal pasteurellaceae species inhibits nontypeable Haemophilus influenzae colonization and delays onset of otitis media in mice. Infect. Immun. 88, e00685-19.
| Nasal delivery of a commensal pasteurellaceae species inhibits nontypeable Haemophilus influenzae colonization and delays onset of otitis media in mice.Crossref | GoogleScholarGoogle Scholar | 31964748PubMed |
