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Luanne Hall-Stoodley, PhD; Fen Ze Hu, PhD; Armin Gieseke, PhD; Laura Nistico, PhD; Duc Nguyen, PhD; Jay Hayes, BS; Michael Forbes, MD; David P. Greenberg, MD; Bethany Dice, BS; Amy Burrows, BS; P. Ashley Wackym, MD; Paul Stoodley, PhD; J. Christopher Post, MD, PhD; Garth D. Ehrlich, PhD; Joseph E. Kerschner, MD

JAMA. 2006;296:202-211.

Context  Chronic otitis media (OM) is a common pediatric infectious disease. Previous studies demonstrating that metabolically active bacteria exist in culture-negative pediatric middle-ear effusions and that experimental infection with Haemophilus influenzae in the chinchilla model of otitis media results in the formation of adherent mucosal biofilms suggest that chronic OM may result from a mucosal biofilm infection.

Objective  To test the hypothesis that chronic OM in humans is biofilm-related.

Design, Setting, and Patients  Middle-ear mucosa (MEM) biopsy specimens were obtained from 26 children (mean age, 2.5 [range, 0.5-14] years) undergoing tympanostomy tube placement for treatment of otitis media with effusion (OME) and recurrent OM and were analyzed using microbiological culture, polymerase chain reaction (PCR)-based diagnostics, direct microscopic examination, fluorescence in situ hybridization, and immunostaining. Uninfected (control) MEM specimens were obtained from 3 children and 5 adults undergoing cochlear implantation. Patients were enrolled between February 2004 and April 2005 from a single US tertiary referral otolaryngology practice.

Main Outcome Measures  Confocal laser scanning microscopic (CLSM) images were obtained from MEM biopsy specimens and were evaluated for biofilm morphology using generic stains and species-specific probes for H influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Effusions, when present, were evaluated by PCR and culture for evidence of pathogen-specific nucleic acid sequences and bacterial growth, respectively.

Results  Of the 26 children undergoing tympanostomy tube placement, 13 (50%) had OME, 20 (77%) had recurrent OM, and 7 (27%) had both diagnoses; 27 of 52 (52%) of the ears had effusions, 24 of 24 effusions were PCR-positive for at least 1 OM pathogen, and 6 (22%) of 27 effusions were culture-positive for any pathogen. Mucosal biofilms were visualized by CLSM on 46 (92%) of 50 MEM specimens from children with OME and recurrent OM using generic and pathogen-specific probes. Biofilms were not observed on 8 control MEM specimens obtained from the patients undergoing cochlear implantation.

Conclusion  Direct detection of biofilms on MEM biopsy specimens from children with OME and recurrent OM supports the hypothesis that these chronic middle-ear disorders are biofilm-related.

Author Affiliations: Center for Genomic Sciences, Allegheny-Singer Research Institute, Pittsburgh, Pa (Drs Hall-Stoodley, Hu, Gieseke, Nistico, Nguyen, Forbes, Stoodley, Post, and Ehrlich and Mr Hayes and Ms Dice); Department of Microbiology and Immunology, Drexel University College of Medicine, Allegheny Campus, Pittsburgh (Drs Hall-Stoodley, Hu, Stoodley, Post, and Ehrlich); Department of Molecular Ecology, Max Planck Institute for Marine Microbiology, Bremen, Germany (Dr Gieseke); Children's Hospital of Pittsburgh, Pittsburgh (Dr Greenberg); and Children's Hospital of Wisconsin, Medical College of Wisconsin, Department of Otolaryngology, Milwaukee (Ms Burrows and Drs Wackym and Kerschner).

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