Comparison of systemic and otic administration of ofloxacin.

OBJECTIVES: To assess the feasibility of delivering ofloxacin across the intact tympanic membrane; to compare middle ear bioavailability of ofloxacin after otic and systemic administrations; to determine distribution of otically delivered ofloxacin to other tissues. STUDY DESIGN: A prospective, controlled animal study. METHODS: Rats underwent surgery wherein the middle ear cavity was opened and filled with saline. An equivalent amount of ofloxacin was delivered intraperitoneally or into the external ear canal. Saline within the middle ear was sampled and completely replaced in 15-minute intervals for 3 hours. Blood was collected twice after the initial application of ofloxacin for high-performance liquid chromatography (HPLC). Animals were sacrificed 3 hours after the initial addition of ofloxacin; the temporal bones were harvested for histological analysis; urine and colon mucosa were collected for HPLC analysis. RESULTS: Both systemic and otic applications led to a comparable accumulation of ofloxacin in the middle ear over the 3-hour period after the initial administration. The pharmacokinetics of ofloxacin penetration into the middle ear was sporadic and subject-dependent. Both methods of administration led to drug accumulation in blood serum, urine, and colonic mucosa. CONCLUSIONS: Topical application of ofloxacin to the intact tympanic membrane allows for drug penetration into the middle ear space. Similar middle ear ofloxacin levels could be achieved with systemic and topic applications, but drug concentrations were inconsistent. The accumulation of ofloxacin in other tissues suggests applications designed to be ototopical may also result in systemic absorption.

Ototoxicity of topical azithromycin solutions in the guinea pig.

OBJECTIVE: To investigate possible ototoxic effects of topical azithromycin (AZ) in the guinea pig. DESIGN: A prospective, controlled animal study. SETTING: The University of Texas Southwestern Medical Center at Dallas. PARTICIPANTS: Twenty-three pigmented guinea pigs were given single, unilateral middle ear applications of a solution containing 3% (n = 3), 2% (n = 5), 1% (n = 5), or 0.5% (n = 5) AZ or saline (n = 5). The contralateral ear served as the untreated control. MAIN OUTCOME MEASURES: The animals were observed for behavioral changes for 2 weeks and then humanely killed. The ears were processed for anatomical evaluation. Morphologic changes were analyzed by quantitation of middle ear changes and cochlear inner and outer hair cell loss. Statistical analysis was performed to examine effects by dose. RESULTS: Analysis revealed extensive middle and inner ear changes associated with all formulations of AZ. Moderate correlation was found between the extent of middle ear changes and AZ concentration (r(2) = 0.59), whereas a strong correlation was seen between inner ear damage and AZ concentration (r(2) = 0.94). Both inner and outer hair cells were affected, with inner hair cell damage consistently greater than outer hair cell damage. CONCLUSIONS: The results of this study demonstrate that ototopical AZ can cause middle ear changes and significant hair cell loss in the guinea pig. This finding, together with previous clinical reports, indicates that topical AZ should be used with caution in the clinical setting.

Controlled release of hepatocyte growth factor from a bovine acellular scaffold for vocal fold reconstruction.

A bovine acellular scaffold was found to facilitate tissue remodeling in a rat model of vocal fold injury, whereas hepatocyte growth factor (HGF) has been shown to have an antiscarring effect in the larynx. This study examined the loading and release kinetics of HGF in vitro, and the potential of the acellular scaffold as a timed-release system for the delivery of HGF in vivo. Bilateral wounds were created in the posterior vocal folds of 20 rats, with HGF-loaded acellular scaffolds implanted into the wounds unilaterally, and scaffolds without HGF implanted into the contralateral vocal folds as control. The rats were humanely sacrificed after 3, 7, 30, and 90 days and their larynges were examined histologically and immunohistochemically. Expressions of key matrix proteins in the vocal fold coronal sections were quantified by digital image analysis. Results demonstrated a gradual, sustained release of HGF for at least 7 days in vitro, consistent with the detection of glycosaminoglycans inherent of the scaffold. In rat vocal folds implanted with HGF-loaded scaffolds, apparently fewer inflammatory cells were observed 3 days after surgery when compared to the control. The mean relative densities of collagen III and hyaluronic acid were significantly lower than those of the control 7 days after surgery. Scaffold implants were apparently degraded by 3 months in all animals, with no evidence of fibrosis or calcification. These data suggested that the bovine acellular scaffold could be promising for the exogenous delivery of select growth factors in vivo.

Bacterial biofilm formation on a human cochlear implant.

OBJECTIVE: To report the characteristics of a bacterial biofilm from the surface of a cochlear implant. BACKGROUND: Bacterial biofilm formation on implanted devices causes intractable infections and device extrusions necessitating device removal, with loss of function. More information is needed about biofilm characteristics and interactions with the implant surface before better treatments can be designed. STUDY DESIGN: A retrospective case review was combined with a descriptive histological study of the surface of an otologic device. METHODS: The receiver/stimulator device removed from a cochlear implant patient because of intractable infection and partial device extrusion was fixed and processed for microscopic examination. Its surface and the material present on its surface were analyzed using light and electron microscopy, focusing on surface texture, cell types, and bacteria species and extracellular polymeric substances present within the biofilm. RESULTS: Stereomicroscopic examination revealed extracellular polymeric substances, pinkish yellow in color, with spheres of uniform size scattered throughout, indicative of a biofilm containing Staphylococcus aureus. Biofilm density was greatest in depressions on the surface of the implant. Cross-sectional analysis revealed bacteria interspersed with polymorphonuclear leukocytes. Scanning electron microscopic examination demonstrated an amorphous layer of extracellular polymeric substances containing small filaments, bacteria, and inflammatory cells. Only Staphylococcus aureus was detected. CONCLUSION: Cochlear implant material can provide a surface for bacterial biofilm formation. Impressions can provide an environment conducive to biofilm establishment and growth, ultimately necessitating device removal, with loss of implant function. Biofilm characterization should aid in design of cochlear implant devices less susceptible to biofilm formation.