Evaluating the ototoxicity of topical piperacillin-tazobactam.
OBJECTIVE
With the increased use of ototopical ciprofloxacin solution, newly evolved bacterial fluoroquinolone resistance has also become more of a problem. The emergence of ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) has created a new therapeutic challenge in otology. We evaluated the ototoxicity of topical fortified piperacillin-tazobactam solution by performing experiments in young male albino guinea pigs (weight, 250-300 g each).


METHODS
Antimicrobial assay by direct contact test using scanning electron microscope was performed. Twenty guinea pigs (250-300 g) were treated with fortified piperacillin-tazobactam solution. In experimental group 1 (n=10), a gelfoam ball impregnated with 120 microl of fortified piperacillin-tazobactam was implanted on the round window membrane by a posterior approach. In experimental group 2 (n=10), 20 microl of fortified piperacillin-tazobactam was injected into the middle ear cavity via silicone tube with a small hole placed in the superior aspect of the bulla by drilling. The drug application through the tube was performed for 7 consecutive days. In control group (n=5), a gelfoam ball impregnated with 120 microl of gentamicin solution (80 mg/2 ml) was implanted on the round window membrane.


RESULTS
The fortified piperacillin-tazobactam 20 microl treated CRPAs showed destruction of their cell membrane in antimicrobial assay by direct contact test. No significant difference in the mean auditory brainstem response (ABR) thresholds before and after drug administration was found for the experimental group. However, significant elevation of the mean ABR thresholds was found for the control group. In experimental group, scanning electron microscopy showed almost normal sterociliary arrangements and surface structure on the inner and outer hair cells. However, significant destruction of outer hair cells was identified in control group.


CONCLUSIONS
This present study's data suggests that fortified piperacillin-tazobactam solution can be effectively used for topically treating CRPA otorrhea in those patients who suffer with chronic suppurative otitis media.
Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea; Research Center for Resistant Cells, Chosun University, Gwangju, South Korea. chulsavio@hanmail.net
Chul-Ho
CH
Jang
Haekyun
H
Park
Yong Bum
YB
Cho
Cheol-Hee
CH
Choi
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects*; D004338:Drug Combinations; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000648:ultrastructure; D000078142:Tazobactam
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin