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评估抗耐甲氧西林金黄色葡萄球菌肽KR-12-a2的耳毒性。

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

作者信息

Sung Chung Man, Kim Hong Chan, Cho Yong Beom, Shin Song Yub, Jang Chul Ho

机构信息

Chonnam National University Medical School, Department of Otolaryngology, Gwangju, South Korea.

Chosun University, School of Medicine, Graduate School and Department of Cellular & Molecular Medicine, Gwangju, South Korea.

出版信息

Braz J Otorhinolaryngol. 2018 Jul-Aug;84(4):441-447. doi: 10.1016/j.bjorl.2017.05.002. Epub 2017 May 31.

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.

摘要

引言

耐甲氧西林金黄色葡萄球菌是慢性化脓性中耳炎治疗中出现的一个新问题,也是小儿鼓膜置管耳漏的新问题。迄今为止,尚无有效的局部用抗生素药物来治疗耐甲氧西林金黄色葡萄球菌耳漏。

目的

在本研究中,我们评估了局部应用KR-12-a2溶液于豚鼠中耳时对耳蜗的耳毒性。

方法

采用抑菌圈试验检测KR-12-a2对耐甲氧西林金黄色葡萄球菌菌株的抗菌活性。在插入通气管后,将KR-12-a2溶液、庆大霉素和磷酸盐缓冲盐水局部应用于豚鼠中耳。通过听性脑干诱发电位和扫描电子显微镜检查评估耳毒性。

结果

KR-12-a2对6.25μg的耐甲氧西林金黄色葡萄球菌产生抑菌圈。KR-12-a2组和磷酸盐缓冲盐水组的听力阈值与插入通气管前相似。然而,庆大霉素组的听力阈值升高,与磷酸盐缓冲盐水组或KR-12-a2组相比有统计学显著差异。在扫描电子显微镜检查结果中,KR-12-a2组的外毛细胞完整。然而,庆大霉素组的外毛细胞完全丧失。在我们的实验中,局部应用KR-12-a2溶液未导致豚鼠听力损失或耳蜗损伤。

结论

在我们的实验中,局部应用KR-12-a2溶液未导致豚鼠听力损失或耳蜗损伤。KR-12-a2溶液可作为局部滴耳剂用于治疗耐甲氧西林金黄色葡萄球菌耳漏;然而,需要进一步评估,如最佳浓度和联合用药的确定。

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