Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2 / Avaliando a ototoxicidade de um peptídeo anti-MRSA KR-12-a2

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.

Role of preoperative air-bone gap in tinnitus outcome after tympanoplasty for chronic otitis media with tinnitus / Papel do gap aéreo-ósseo pré-operatório no desfecho do zumbido após timpanoplastia para otite média crônica com zumbido

Abstract Introduction Previous reports indicated that middle ear surgery might partially improve tinnitus after surgery. However, until now, no influencing factor has been determined for tinnitus outcome after middle ear surgery. Objective The purpose of this study was to investigate the association between preoperative air-bone gap and tinnitus outcome after tympanoplasty type I. Methods Seventy-five patients with tinnitus who had more than 6 months of symptoms of chronic otitis media on the ipsilateral side that were refractory to medical treatment were included in this study. All patients were evaluated through otoendoscopy, pure tone/speech audiometer, questionnaire survey using the visual analog scale and the tinnitus handicap inventory for tinnitus symptoms before and 6 months after tympanoplasty. The influence of preoperative bone conduction, preoperative air-bone-gap, and postoperative air-bone-gap on tinnitus outcome after the operation was investigated. Results and conclusion The patients were divided into two groups based on preoperative bone conduction of less than 25 dB (n = 50) or more than 25 dB (n = 25). The postoperative improvement of tinnitus in both groups showed statistical significance. Patients whose preoperative air-bone-gap was less than 15 dB showed no improvement in postoperative tinnitus using the visual analog scale (p = 0.889) and the tinnitus handicap inventory (p = 0.802). However, patients whose preoperative air-bone-gap was more than 15 dB showed statistically significant improvement in postoperative tinnitus using the visual analog scale (p < 0.01) and the tinnitus handicap inventory (p = 0.016). Postoperative change in tinnitus showed significance compared with preoperative tinnitus using visual analog scale (p = 0.006). However, the correlation between reduction in the visual analog scale score and air-bone-gap (p = 0.202) or between reduction in tinnitus handicap inventory score and air-bone-gap (p = 0.290) was not significant. We suggest that the preoperative air-bone-gap can be a predictor of tinnitus outcome after tympanoplasty in chronic otitis media with tinnitus.

Resumo Introdução Relatos anteriores indicaram que a cirurgia no ouvido médio pode melhorar parcialmente o zumbido após a cirurgia. No entanto, até agora, nenhum fator influenciador foi determinado para o resultado do zumbido após cirurgia de ouvido médio. Objetivo O objetivo deste estudo foi investigar a associação entre o gap aéreo-ósseo pré-operatório e o desfecho do zumbido após timpanoplastia do tipo I. Método Setenta e cinco pacientes com zumbido, com mais de 6 meses de sintomas de otite média crônica no lado ipsilateral que eram refratários ao tratamento médico foram incluídos nesse estudo. Todos os pacientes foram avaliados através de otoendoscopia, audiometria tonal/vocal, questionário utilizando a escala visual analógica e o questionário tinnitus handicap inventory para sintomas de zumbido antes e 6 meses após a timpanoplastia. A influência da condução óssea pré-operatória, gap aéreo-ósseo pré-operatório e pós-operatório sobre o desfecho do zumbido após a operação foi analisada. Resultados e conclusão Os pacientes foram divididos em dois grupos com base na condução óssea pré-operatória de menos de 25 dB (n = 50) ou mais de 25 dB (n = 25). A melhora do zumbido pós-operatória em ambos os grupos mostrou significância estatística. Pacientes com gap aéreo-ósseo pré-operatório inferior a 15 dB não apresentaram melhora no zumbido pós-operatório utilizando a escala visual analógica (p = 0,889) e o tinnitus handicap inventory (p = 0,802). Entretanto, pacientes com gap aéreo-ósseo pré-operatório maior do que 15 dB apresentaram melhoria estatisticamente significante no zumbido pós-operatório com a escala visual analógica (p < 0,01) e o tinnitus handicap inventory (p = 0,016). A mudança pós-operatória no zumbido mostrou significância em comparação com o zumbido pré-operatório usando a escala visual analógica (p = 0,006). No entanto, a correlação entre a redução no escore da escala visual analógica e gap aéreo-ósseo (p = 0,202) ou entre a redução no escore do tinnitus handicap inventory e gapaéreo-ósseo (p = 0,290) não foi significativa. Sugerimos que o gapaéreo-ósseo pré-operatório possa ser um preditor de desfecho do zumbido após timpanoplastia em otite média crônica com zumbido.

Role of preoperative air-bone gap in tinnitus outcome after tympanoplasty for chronic otitis media with tinnitus.

INTRODUCTION: Previous reports indicated that middle ear surgery might partially improve tinnitus after surgery. However, until now, no influencing factor has been determined for tinnitus outcome after middle ear surgery. OBJECTIVE: The purpose of this study was to investigate the association between preoperative air-bone gap and tinnitus outcome after tympanoplasty type I. METHODS: Seventy-five patients with tinnitus who had more than 6 months of symptoms of chronic otitis media on the ipsilateral side that were refractory to medical treatment were included in this study. All patients were evaluated through otoendoscopy, pure tone/speech audiometer, questionnaire survey using the visual analog scale and the tinnitus handicap inventory for tinnitus symptoms before and 6 months after tympanoplasty. The influence of preoperative bone conduction, preoperative air-bone-gap, and postoperative air-bone-gap on tinnitus outcome after the operation was investigated. RESULTS AND CONCLUSION: The patients were divided into two groups based on preoperative bone conduction of less than 25dB (n=50) or more than 25dB (n=25). The postoperative improvement of tinnitus in both groups showed statistical significance. Patients whose preoperative air-bone-gap was less than 15dB showed no improvement in postoperative tinnitus using the visual analog scale (p=0.889) and the tinnitus handicap inventory (p=0.802). However, patients whose preoperative air-bone-gap was more than 15dB showed statistically significant improvement in postoperative tinnitus using the visual analog scale (p<0.01) and the tinnitus handicap inventory (p=0.016). Postoperative change in tinnitus showed significance compared with preoperative tinnitus using visual analog scale (p=0.006). However, the correlation between reduction in the visual analog scale score and air-bone-gap (p=0.202) or between reduction in tinnitus handicap inventory score and air-bone-gap (p=0.290) was not significant. We suggest that the preoperative air-bone-gap can be a predictor of tinnitus outcome after tympanoplasty in chronic otitis media with tinnitus.

Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2.

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.