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Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2
Chung Man Sung1, Hong Chan Kim1, Yong Beom Cho1
1Chonnam National University Medical School, Department of Otolaryngology, Gwangju, South Korea.
Introduction:
Methicillin-resistant staphylococcus aureus is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat methicillin-resistant staphylococcus aureus otorrhea.
Objective:
In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it is applied topically in the middle ear of guinea pigs.
Methods:
The antimicrobial activity of KR-12-a2 against methicillin-resistant staphylococcus aureus strains was examined by using the inhibition zone test. Topical application of KR-12-a2 solution, gentamicin and phosphate buffered saline were applied in the middle ear of the guinea pigs after inserting ventilation tubes. Ototoxicity was assessed by auditory brainstem evoked response and scanning electron microscope examination.
Results:
KR-12-a2 produced an inhibition zone against methicillin-resistant staphylococcus aureus from 6.25 μg. Hearing threshold in the KR-12-a2 and PBS groups were similar to that before ventilation tube insertion. However, the gentamicin group showed elevation of the hearing threshold and there were statistically significant differences compared to the phosphate buffered saline or the KR-12-a2 group. In the scanning electron microscope findings, the KR-12-a2 group showed intact outer hair cells. However, the gentamicin group showed total loss of outer hair cells. In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs.
Conclusion:
In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. The KR-12-a2 solution can be used as ototopical drops for treating methicillin-resistant staphylococcus aureus otorrhea; however, further evaluations, such as the definition of optimal concentration and combination, are necessary.
Insights
Topical KR-12-a2 solution effectively treated methicillin-resistant staphylococcus aureus otorrhea in guinea pigs without causing cochlear damage or hearing loss. Further studies are needed to determine optimal concentrations.
Area of Science:
- Otolaryngology
- Infectious Diseases
- Pharmacology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) presents a growing challenge in treating chronic suppurative otitis media and pediatric tympanostomy tube otorrhea.
- Currently, no effective topical antibiotics exist to combat MRSA otorrhea.
Purpose of the Study:
- To assess the ototoxicity of topical KR-12-a2 solution on the cochlea when administered to the middle ear in guinea pigs.
- To evaluate the antimicrobial efficacy of KR-12-a2 against MRSA.
Main Methods:
- Antimicrobial activity of KR-12-a2 against MRSA was determined using the inhibition zone test.
- Guinea pigs received topical KR-12-a2, gentamicin, or phosphate-buffered saline (PBS) in the middle ear post-ventilation tube insertion.
- Ototoxicity was evaluated via auditory brainstem evoked response and scanning electron microscopy.
Main Results:
- KR-12-a2 demonstrated antimicrobial activity against MRSA starting at 6.25 μg.
- Hearing thresholds in the KR-12-a2 and PBS groups remained stable, unlike the gentamicin group which showed significant hearing threshold elevation.
- Scanning electron microscopy revealed intact outer hair cells in the KR-12-a2 group, contrasting with the complete loss observed in the gentamicin group.
Conclusions:
- Topical KR-12-a2 solution applied to the middle ear of guinea pigs did not induce hearing loss or cochlear damage.
- KR-12-a2 shows potential as an ototopical treatment for MRSA otorrhea, though further research on optimal concentration and combinations is required.
