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Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
Evaluating the ototoxicity of topical piperacillin-tazobactam
Chul-Ho Jang1, Haekyun Park, Yong Bum Cho
1Department of Otolaryngology, Chonnam National University Medical School, Gwangju, South Korea; Research Center for Resistant Cells, Chosun University, Gwangju, South Korea. chulsavio@hanmail.net
Background And 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).
Materials And 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.
Conclusion:
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.
Insights
Fortified piperacillin-tazobactam shows efficacy against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) in otorrhea. This topical solution demonstrates low ototoxicity in guinea pigs, offering a potential new treatment for chronic suppurative otitis media.
Area of Science:
- Otolaryngology
- Microbiology
- Pharmacology
Background:
- Increasing bacterial fluoroquinolone resistance, particularly ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA), poses a therapeutic challenge in otology.
- Topical ciprofloxacin solutions have contributed to the rise of CRPA, necessitating alternative treatments.
Purpose of the Study:
- To evaluate the ototoxicity of topical fortified piperacillin-tazobactam solution.
- To assess the efficacy of piperacillin-tazobactam against CRPA in an otological context.
Main Methods:
- Antimicrobial activity of piperacillin-tazobactam against CRPA was assessed using direct contact tests and scanning electron microscopy.
- Ototoxicity was evaluated in guinea pigs using auditory brainstem response (ABR) and scanning electron microscopy of cochlear hair cells.
- Experimental groups received topical piperacillin-tazobactam via gelfoam implantation or middle ear injection; a control group received gentamicin.
Main Results:
- Piperacillin-tazobactam demonstrated antimicrobial effects, causing cell membrane destruction in CRPA.
- No significant changes in auditory brainstem response (ABR) thresholds were observed in the piperacillin-tazobactam treated groups.
- Scanning electron microscopy revealed preserved inner and outer hair cell structures in the experimental groups, unlike the control group.
Conclusions:
- Topical fortified piperacillin-tazobactam solution is a potentially effective and safe treatment for CRPA otorrhea.
- This antibiotic may be a viable option for patients with chronic suppurative otitis media and CRPA infections.
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