Mounting evidence suggests that bacterial biofilms play a role in chronic inflammatory infections of the middle ear and sinuses. Whether these biofilms actually cause chronic ear and sinus infections remains unproven, but it is increasingly shown from a number of animal studies and a recently published human study that biofilms are present in these chronic otolaryngologic conditions.
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January 2007
Biofilms are a relatively novel way of looking at bacteria, said Martin Desrosiers, MD, Department of Otolaryngology, Head and Neck Surgery at McGill University in Montreal, who, along with his colleagues, has examined the role of biofilms in chronic sinusitis. A number of people [studying] chronic sinusitis have found that there are biofilms that are present, he said. So this is quite a revelation that gives us a new therapeutic target.
Although much of the published data showing the presence of biofilms in chronic sinusitis and chronic otitis media have been in animal studies, a recently published study in humans now adds weight to the evidence of the presence of biofilms in these chronic conditions.
Conducted by researchers at the Allegheny-Singer Research Institute in Pittsburgh, the study examined the presence of biofilms in children with chronic otitis media. Investigators used confocal laser scanning microscope images to evaluate the presence of biofilms in the middle-ear muscosa of biopsy specimens taken from 26 children undergoing tympanostomy tube placement for treatment of otitis media with effusion and recurrent otitis media. They compared these images to specimens biopsied in 8 patients undergoing cochlear implantation, who served as the control group.
Mucosal biofilms were detected in 92% of the biopsied specimens of the 26 children undergoing tympanostomy tube placement, whereas no biofilms were found in the 8 control patients.
The key finding [of the study] is that chronic otitis media is associated with a bacterial biofilm, said J. Christopher Post, MD, PhD, Professor of Otolaryngology at Drexel University College of Medicine in Pittsburgh, one of the coauthors of the study. The conventional wisdom is that while acute otitis media is a bacterial process, chronic otitis media is a sterile, inflammatory process. Investigators came to this erroneous conclusion because cultures of chronic middle-ear effusions are generally sterile. But the mistake was that ‘no growth of bacteria’ was interpreted to mean ‘bacteria are not there.’
The study highlighted the importance of accurate detection of bacterial biofilms by using a combination of microbiological culture, polymerase chain reaction (PCR)-based diagnostics, direct microscopic examination, fluorescence in situ hybridization, and immunostaining. According to Dr. Post, relying upon culture techniques to claim that bacteria are not present is clinging to old-fashioned technology.
For Richard A. Chole, MD, PhD, Lindburg Professor and Chairman of the Department of Otolaryngology at Washington School of Medicine in St. Louis, this was a landmark study that builds on prior observations of the presence of live bacteria in chronic middle-ear effusions. However, he reiterated that causation between these bacterial biofilms and chronic middle-ear effusions and inflammation still remains unknown.
The most parsimonious explanation is that the biofilm forms on the epithelial surface and then produces inflammatory factors, endotoxins and exotoxins, that maintain an inflammatory state, he said. Nevertheless, critics will demand that the causation question be answered.
Although acknowledging that biofilms play an integral part in the pathogenesis of these chronic otolaryngological conditions, Hassan H. Ramadan, MD, MSc, Professor and Vice Chairman of the Department of Otolaryngology-Head and Neck Surgery at West Virginia University in Morgantown, W. Va., raised a question that speaks to the need to demonstrate causality. If biofilms are present in the middle-ear mucosa of the majority of kids in the study, why do some of these kids have episodes of no fluid in their middle ears and no symptoms?
This question and others remain to be answered, but the recognition that biofilms are present in these chronic conditions suggests to all these experts the need to rethink the way in which antibiotics are used to treat these conditions.
If biofilms are involved in these cases, then supposedly higher doses of antibiotics than we usually use are needed to treat these individuals, said Dr. Ramadan, and even so may not be successful.
Dr. Desrosiers agrees. Treating them [bacteria] with regular doses of antibiotics is not sufficient. Even when you can kill them with high doses of antibiotics, a certain number persist.
The lack of efficacy of antibiotics for these chronic conditions is one reason investigators have started looking at mechanisms of infection, such as biofilms, that may be targeted to prevent ongoing or recurrent infection.
According to Dr. Chole, antibiotics will be only partially effective to treat these chronic conditions if bacterial biofilms are involved because of the altered phenotype of these bacteria that are highly resistant to antibiotics. The bacteria in a biofilm are in equilibrium with planktonic, motile bacteria, he said. In their planktonic phenotype bacteria may be sensitive to the antibiotic so the antibiotic may ameliorate the disease without destroying the underlying biofilm.
This phenomenon may explain why chronic sinus and ear infections seem to respond to antibiotics and then recur again after the antibiotics are stopped, he added.
For Dr. Desrosiers, this altered phenotype of biofilms that allows bacteria to persist despite antibiotic use does not suggest that antibiotics are not needed. He emphasized the continual need for antibiotics when bacteria flare up and infection sets in, but stressed that ongoing or recurrent infections may be prevented if biofilms are eradicated.
This does not lead to less use of antibiotics, he said. At this point in time, it [biofilms] just gives us another piece of the puzzle. In terms of what it means for the patient today, it means nothing.
What the current data do support, however, is the efficacy of ventilation (tubes) or mechanical debridement (such as teeth brushing) to eradicate chronic infection. Biofilms explain why chronic middle-ear infections are so refractory to antimicrobial usage and why tubes are effective, said Dr. Post.
According to Dr. Desrosiers, tubes change the niche that the biofilm occupies by allowing oxygen to enter the middle ear and changing the local environment where biofilms exist and subsequently clearing up inner ear disease.
But if a causal relationship between biofilms and chronic infection can be made, prevention of biofilms and not eradication is suggested as the best way to reduce ongoing and recurrent infection and the frequency and amount of antibiotics used.
For Dr. Post, development of a probiotic approach may be the way to go to manage these chronic conditions where we populate the patient with innocuous bacteria that prevent the formation of pathogenic bacterial biofilms.
Other approaches needing further investigation may be through the use of lactoferrin and furanones, according to Dr. Chole. Lactoferrin is a protein in the body that helps defend against bacteria by trapping iron, which is a critical nutrient for bacteria. Furanones are chemicals that protect against bacteria in marine algae.
Until further evidence supports a causal link between biofilms and chronic infection, however, antibiotic use will remain the mainstay of treatment for ongoing and recurrent infections. However, as more data accumulate that demonstrate the presence of biofilms in chronic sinus and middle ear infections, a new therapeutic target aimed at prevention may eventually allow for a reduction in the use of antibiotics.
In the next two to three years you will see radical changes in the way we manage diseases, said Dr. Desrosiers. Once we do find effective strategies for dealing with biofilms, we will have a reduction in the quantity of antibiotics used.
©2007 The Triological Society