Biofilms May Be Source of Recurrent Otitis Media

PITTSBURGH, July 11 -- Bacterial biofilms colonizing the middle ear - and not re-infections -- may be the cause of recurrent otitis media, according to investigators here.

Biofilms consist of aggregated bacteria, usually adherent to a surface, surrounded by an extracellular matrix, and have been implicated in several chronic bacterial infections. They are typically resistant to antibiotics.

Using a variety of techniques, the researchers found direct evidence of biofilms in the middle ears of 26 children who suffer from chronic ear infections, said Garth Ehrlich, Ph.D., of the Allegheny Singer Research Institute.

Middle ear tissue from a control group of unaffected children showed no sign of biofilms, Dr. Ehrlich and colleagues reported in the July 12 issue of the Journal of the American Medical Association.

"Nearly all of the children in our study who suffered from chronic otitis media tested positive for biofilms in the middle ear, even those who were asymptomatic," Dr. Ehrlich said. "It appears that in many cases recurrent disease stems not from re-infection as was previously thought and which forms the basis for conventional treatment, but from a persistent biofilm."

"Given that bacteria living in biofilms are metabolically resistant to antibiotics, this study makes a definitive, scientifically-based statement against the use of these drugs to treat children with chronic ear infections," Dr. Ehrlich said. "It simply does not help the child and increases the risk of breeding more resistant strains of bacteria."

Dr. Ehrlich and his collaborator, Joseph Kerschner, M.D., of the Medical College of Wisconsin in Milwaukee, proposed the notion that biofilms might explain the persistence of ear infections and the relative inefficacy of antibiotics in many children. In 2002, they showed that biofilms form on the middle ear of the chinchilla - the first animal evidence that the theory might hold water.

To test the idea in humans, they obtained biopsy samples of middle ear mucosa from 26 children undergoing tympanostomy tube placement for treatment of otitis media with effusion and recurrent otitis media. They also obtained samples from control subjects -- three children and five adults undergoing cochlear implantation.

Using a confocal laser scanning microscope, the researchers evaluated the specimens for biofilm morphology with generic stains and species-specific probes for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the major pathogens associated with otitis media.

If there was an effusion, the researchers evaluated it by polymerase chain reaction methods for evidence of pathogen-specific nucleic acid sequences and also by culture for bacterial growth.

The study found:

• No evidence of biofilms or infections among the control subjects.
• Among the children with recurrent otitis media, biofilms were found on 46 of 50 specimens - or 92% -- evaluated by the laser scanning microscope.
• Of 24 effusions tested by PCR, all were positive for at least one otitis media pathogen, and six (or 22%) of 27 effusions tested by culture were positive for any pathogen.

"Today's study completely alters the concept about how physicians should approach the treatment of children with otitis media," Dr. Kerschner said. "This historic finding sheds new light on the decreasing efficacy of antibiotics in treating kids with ear infections and has serious implications about the future direction of therapeutic research."

The typical resistance to antibiotics is likely due to several factors, the investigators said.

• Oxygen and nutrient limitation within biofilms induces metabolic quiescence, which in turn reduces antibiotic effectiveness.
• Biofilm bacteria may have genetic mechanisms, selected for in the biofilm, that provide antimicrobial protection.
• The biofilm provides a physical barrier that enhances pathogen resistance to host defenses such as opsonization, lysis by complement, and phagocytosis.

On the other hand, Dr. Kerschner said, "until something new comes along, placement of ear tubes to provide children with symptomatic relief will still be necessary and recommended (and) antibiotics should also continue to be prescribed for acute otitis media to help prevent potentially serious complications, such as mastoiditis and meningitis."

The investigators pointed out that "Importantly, the findings from our study do not exclude other potential pathogenic factors associated with chronic otitis media with effusion, such as an antecedent viral upper respiratory infection, eustachian tube dysfunction with impaired gas exchange, a genetically predisposed host, persistent inflammatory mediators, or exacerbation by gastroesophageal reflux".

However, they said "these findings do argue against the notion that otitis media with effusion is the result of a nonbacterial inflammatory process and also indicate that equating culture negativity and absence of bacteria is incorrect.