ABSTRACT
Abstract 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.
Resumo Introdução O staphylococcus aureus resistente à meticilina é um problema emergente não só para a otite média supurativa crônica, mas também para casos de otorreia crônica em crianças com tubo de ventilação. Até o momento, não há antibióticos tópicos efetivos para a otorreia causada por staphylococcus aureus resistente à meticilina. Objetivo Nesse estudo, avaliamos a ototoxicidade da solução tópica de KR-12-a2 na cóclea quando aplicada topicamente na orelha média de cobaias. Método A atividade antimicrobiana de KR-12-a2 contra cepas de staphylococcus aureus resistente à meticilina foi avaliada utilizando-se o teste de zona de inibição de crescimento. Foram aplicados na orelhas médias de 3 grupos de cobaias, ou solução tópica de KR-12-a2, ou gentamicina ou solução salina tamponada com fosfato após timpanostomia. A ototoxicidade foi avaliada através do exame auditivo de potencial evocado auditivo de tronco encefálico e por microscopia eletrônica de varredura. Resultados O KR-12-a2 produziu uma zona de inibição contra o staphylococcus aureus resistente à meticilina a partir de 6,25 µg. Alterações do limiar de audição no grupo KR-12-a2 e no grupo com solução salina foram semelhantes aos observados antes da inserção do tubo de ventilação. No entanto, o grupo gentamicina apresentou um limiar auditivo mais elevado, estatisticamente significativo em comparação ao grupo solução salina ou ao grupo KR-12-a2. Nos achados da microscopia eletrônica, o grupo KR-12-a2 apresentou células ciliadas externas intactas. No entanto, o grupo gentamicina apresentou perda total das células ciliadas externas. Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. Conclusão Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. A solução de KR-12-a2 pode ser utilizada como gotas otológicas para o tratamento da otorreia causada por staphylococcus aureus resistente à meticilina; no entanto, são necessárias outras avaliações, para a definição da concentração e das associações ideais.
Subject(s)
Animals , Male , Peptide Fragments/toxicity , Cochlea/drug effects , Cathelicidins/toxicity , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/toxicity , Otitis Media, Suppurative/microbiology , Peptide Fragments/administration & dosage , Auditory Threshold , Staphylococcal Infections/drug therapy , Microscopy, Electron, Scanning , Microbial Sensitivity Tests , Reproducibility of Results , Administration, Topical , Evoked Potentials, Auditory, Brain Stem , Treatment Outcome , Cochlea/physiopathology , Disease Models, Animal , Cathelicidins/administration & dosage , Guinea Pigs , Hair Cells, Auditory/drug effects , Anti-Bacterial Agents/administration & dosageABSTRACT
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.