High concentrations of middle ear antimicrobial peptides and proteins and proinflammatory cytokines are associated with detection of middle ear pathogens in children with recurrent acute otitis media.

Elke J Seppanen,Angela Fuery,Caitlyn M Granland,Ruth B Thornton,Selma P Wiertsema,Julie Hibbert,Shyan Vijayasekaran,Lea-Ann S Kirkham,Peter C Richmond,Karli J Corscadden,Harvey L Coates,Andrew Currie,Peter Jacoby,Y Peter Di

doi:10.1371/journal.pone.0227080

Abstract

Recurrent and chronic otitis media (OM) are often refractory to antibiotics due to bacterial persistence in biofilm within the middle ear. In vitro and in vivo studies have demonstrated that antimicrobial proteins and peptides (AMPs) are bactericidal against otopathogens, indicating potential therapeutic value for recalcitrant OM. We measured concentrations of 6 AMPs and 14 cytokines in middle ear effusion (MEE) from 67 children undergoing ventilation tube insertion for recurrent acute OM. Sixty one percent of children had bacterial otopathogens detected in their MEE, 39% by PCR and 22% by PCR and culture. Groups were defined as: PCR-negative/culture-negative (absence of bacterial otopathogen), n = 26; PCR-positive/culture-negative (presence of nonculturable bacterial otopathogen), n = 26; PCR-positive/culture-positive (presence of culturable bacterial otopathogen), n = 15. Age, antibiotic usage, day-care attendance, presence of respiratory viruses in MEE and number of AOM episodes were similar between groups. AMP and cytokine concentrations were higher in children with bacterial otopathogens in their MEE compared to those with no bacterial otopathogens. Median concentrations of AMPs (except HBD2) were 3 to 56-fold higher in MEE from children with bacterial otopathogens detected in their MEE (P ≤ 0.01). Similarly, median cytokine concentrations (except TGFβ) were >16-fold higher in MEE with bacterial otopathogens detected (P ≤ 0.001). This is the first study to measure AMPs in MEE and together with the cytokine data, results suggest that elevated AMPs and cytokines in MEE are a marker of inflammation and bacterial persistence. AMPs may play an important role in OM pathogenesis.

Highlights

Otitis media (OM) is a common paediatric disease, and in high income countries OM is the primary reason that young children visit their General Practitioner, are prescribed antibiotics and undergo surgery [1]
When current antibiotic usage was compared between children with PCR+ve/culture-ve middle ear effusion (MEE) to those with PCR+ve/culture+ve MEE, there was a trend for fewer positive cultures from children who were on antibiotics at the time of ventilation tube insertion; P = 0.07)
AMP and cytokine concentrations were compared between children that had bacterial otopathogens present in their MEE compared to those who did not

Summary

Introduction

Otitis media (OM) is a common paediatric disease, and in high income countries OM is the primary reason that young children visit their General Practitioner, are prescribed antibiotics and undergo surgery [1]. Complications from recurrent and/or chronic OM include hearing loss and speech delay [2]. These sequelae contribute to a significant social and economic burden of OM on families and healthcare systems [3, 4]. Both bacteria and viruses are implicated in OM aetiology [5], with bacteria more often associated with chronic and recurrent OM [6]. The major bacterial species that are associated with OM are nontypeable Haemophilus influenzae (NTHi), Streptococcus pneumoniae and Moraxella catarrhalis, with NTHi being the most frequently detected species from the middle ear of children with recurrent and chronic OM [6]. To reduce the global burden of OM, especially recurrent and chronic OM, new strategies that target bacterial otopathogens are urgently required

Methods

Results

Conclusion