Structural features of tympanostomy tube biofilm formation in ciprofloxacin-resistant Pseudomonas otorrhea
Introduction
Acute tympanostomy tube otorrhea is a common problem [1], [2], [3] that mainly occurs with upper respiratory infection [4]. In children with tympanostomy tubes, acute otitis media can be diagnosed in the presence of acute otorrhea and acute symptoms. The causative pathogens in young children with acute otorrhea are the same as those found in acute otitis media with an intact tympanic membrane [5]. Recently the most frequently isolated organism is Pseudomonas aeruginosa[6].
The lack of consensus concerning the best treatment is due to the lack of randomized controlled studies in well-defined populations [7], [8]. Nonetheless, recommendations suggest systemic antibiotic treatment in children with concomitant respiratory infection [9]. On the other hand, topical otic solutions, especially fluoroquinolones, are often recommended for the treatment of tympanostomy tube otorrhea. Goldblatt et al. [10] compared the safety and efficacy of ofloxacin otic solution, 0.3% with that of Augmentin oral suspension in pediatric subjects 1–12 years of age with tympanostomy tubes and acute purulent otorrhea. Overall eradication rates for ofloxacin otic solution and Augmentin oral suspension were similar for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and were superior with ofloxacin otic solution for Staphylococcus aureus and P. aeruginosa.
As the clinical application of the topical ciprofloxacin solution has increased, newly evolved bacterial fluoroquinolone resistance has become an increasing problem. Due to the resistance of P. aeruginosa and the development of resistance during therapy, the selection of optimal treatment for this pathogen is often complicated.
Bacterial biofilm is a polysaccharide formation believed to be an important mediator of infection at the site of implanted materials. [11], [12] The organisms within this polysaccharide matrix, or glycocalyx slime layer, are relatively resistant to antibiotics and can become a source of persistent and relapsing infection, often necessitating the removal of the implanted material. [13] Bacterial biofilm formation has been implicated in the high rate of persistent otorrhea after tympanostomy tube insertion. [14], [15], [16] In this study, we evaluated the formation of Pseudomonal biofilm in the presence of intractable posttympanostomy tube otorrhea in children.
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Materials and methods
Twelve patients (seven males, five females) with unilateral posttympanostomy tube with P. aeruginosa otorrhea were evaluated prospectively. The average duration of drainage for the current ear infection studied was 21 days (range 7–36 days). All patients were treated with ciprofloxacin-hydrocortisone otic drops (CiproBay®HC, Alcon Co., USA) but the otorrhea failed to resolve. Ear discharge for culture was collected from the external auditory canal using a swab. The MIC for each strain was
Results
In all cases, ciprofloxacin-resistant P. aeruginosa was the only organism grown.
The all strains exhibited median MICs of 4 mg/l. Thus exceeding the value normally regarded as reference value for resistance in systemic therapy (MIC ≥2 mg/l).
The surface of the silicone tube contained undulations or microfissures throughout. The thick biofilms present on most tube surfaces were densities with no intervening spaces, consistent with biofilms (Fig. 1, Fig. 2).
The focal biofilms present on tube surface
Discussion
Schneider [18] cultured drainage from 100 cases of posttympanostomy tube otorrhea, and reported finding the typical pathogens usually identified from acute otitis media much more commonly in the drainage from children younger than 3 years of age, whereas Pseudomonas and S. aureus pathogens were much more common in children older than 3 years of age.
The development of resistant bacterial organisms to antibiotic therapy is an increasing problem for physicians treating a variety of infections. The
Conclusion
Ciprofloxacin-resistant P. aeruginosa can form on tympanostomy tubes placed in the ears of children. Biofilms can be directly observed by scanning electron microscopy in such implanted tubes. From these results, we conclude that bacterial aggregates called biofilms, resistant to treatment by antibiotics and to detection by standard culture techniques, may play a major etiologic role in posttympanostomy otorrhea.
Acknowledgements
This study was supported by grants from Ministry of Science and Technology, Korea, and from Korea Science and Engineering Foundation through Research Center for Resistant Cells (R13-2003-009).
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