Middle Ear Infections are Caused by Biofilm Formation

Otitis media (OM) is the most common illness for which children visit a healthcare provider in the United States. It is also the most prevalent reason for prescribing antibiotic therapy or a surgical procedure with general anesthesia in children. OM is associated with significant illness possibly leading to conductive hearing loss, a condition linked to delays in achieving developmental milestones for language acquisition and socialization skills. Now, a new study being presented before the nations leading pediatric otolaryngologists confirms that this disorder is in fact a biofilm disease.

Three bacterial pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are typically isolated from children with acute otitis media. Culture of the effusion from children with OME using traditional microbiological methodology, however fails to support growth of bacteria between 30 percent and 50 percent of the time. The prevalence of these sterile effusions led to the hypothesis that otitis media with effusion was not associated with active bacterial infection, but rather was a protracted inflammatory response to previous infection.

However, some studies over the past decade identified the presence of DNA specific for the three dominant bacterial OM pathogens in culture-negative effusions, suggesting that nearly 80 percent of OME cases, involved bacteria. Subsequently the presence of pathogen-specific mRNA, a labile molecule with a very short half-life, was demonstrated in 100 percent of DNA-positive, sterile effusions convincingly demonstrating that viable bacteria are present in OME.

Evidence that OME is associated with persistent bacterial infection in the absence of culture, in addition to its refractoriness to antibiotic treatment suggested a new category was needed to better understand the pathophysiology of OME. Researchers have hypothesized that OME results from the formation of a bacterial biofilm on the mucosal surface of the middle ear. Biofilms consist of aggregated bacteria adherent to a surface and surrounded by a protective matrix of complex composition. A notable feature of biofilm bacteria is their remarkable resistance to antimicrobial treatment. Within the biofilm are numerous environmental niches that promote a plurality of metabolic states that collectively protect the biofilm population from suboptimal or deleterious environmental conditions.

Therefore, a hypothesis exists that chronic otitis media is the result of biofilm development on the surface of the mucosal epithelium in the middle ear closely parallels other biofilm infections and integrates a broader range of experimental and clinical observations associated with this disease.

Previous studies with low passage clinical isolates of H. influenzae have demonstrated that mucosal biofilms are present on chinchilla middle-ear mucosal epithelium in animals infected experimentally with H. influenzae. Pneumococcal biofilms, however have not been previously demonstrated in this animal model. No studies have directly examined human tissue for evidence of biofilm development on the middle ear mucosa (MEM).

A new study has set out to characterize pneumococcal biofilm ultrastructure first in vitro, and second in vivo in the chinchilla model of otitis media with effusion. The authors of Direct Detection of Streptococcus pneumoniae and Haemophilus influenzae Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media, are Luanne Hall Stoodley, Ph.D, Fen Ze Hu, Ph.D. Garth D. Ehrlich, PhD (Drs Hu and Erlich are also affiliated with the Drexel University College of Medicine), Armin Gieseke PhD, Laura Nistico, PhD, Duc Nguyen1 PhD, Bethany Dice, Paul Stoodley, PhD, J. Christopher Post MD Ph.D, and Jay Hayes, all with the Center for Genomic Sciences, Allegheny-Singer Research Institute, Pittsburgh, PA; Michael Forbes MD and David P. Greenberg MD at the Childrens Hospital of Pittsburgh, Pittsburgh, PA, and Joseph Kerschner MD, and Amy Burrows from the Childrens Hospital of Wisconsin, Medical College of Wisconsin, Department of Otolaryngology, Milwaukee, WI. Their findings will be presented at the 20th annual meeting of the American Society of Pediatric Otolaryngology (ASPO) being held May 27-30, 2005 in Las Vegas.

Methodology: This research was a prospective case series. Patients scheduled for tympanostomy tube placement insertion underwent aerobic culture and polymerase chain reaction (PRC) assessment for Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis if ME fluid was present. ME tissue biopsies were assessed for biofilms using confocal microscopy and bacterial stains.

Results: nine patients were assessed. Six patients had a diagnosis of OME and three with ROM. Of these patients, 44 percent demonstrated biofilm formation and 44 percent demonstrated microscopy suggestive of biofilm formation. One patient had a positive ME pathogen on routine culture, but all patients with ME fluid were positive for ME pathogens by PCR.

Conclusions: This study is the first to demonstrate that OM in humans is mediated by biofilm formation. Biofilm bacteria are difficult to culture, also confirmed in this study. Biofilm bacteria are resistant to antibiotic treatment and predispose the host to indolent and long-term infectious processes, normally characteristic of the middle ear infection in these patients. Identification of OM as a biofilm disease in humans has significant implications in researchers understanding of OM pathophysiology and in developing treatment paradigms for OM.