A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats.
A single dose of epidermicin NI01 is sufficient to eradicate MRSA from the nares of cotton rats.
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DOI：
10.1093/jac/dkw457
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发表时间：
2017-03-01
期刊：
影响因子：
--
通讯作者：
Upton M
中科院分区：
文献类型：
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作者：
Halliwell S;Warn P;Sattar A;Derrick JP;Upton M
目的：在棉鼠（Sigmodon hispidus）模型中，研究一种6 kDa的有效新型抗菌蛋白--表皮霉素NI01消除MRSA鼻腔负荷的有效性。方法：使用MRSA菌株ATCC 43300建立棉鼠鼻孔的稳健定殖。该模型用于评价局部0.04%和0.2%表皮霉素NI01每日两次给药连续3天以及局部0.8%表皮霉素NI01给药一次降低鼻腔MRSA负荷的疗效。对照组保持未处理或仅给予媒介物（0.5%羟丙基甲基纤维素）或2%莫匹罗星，每天两次，持续3天。实验在第5天终止，并测定MRSA定量计数。检查从每天两次用0.2%表皮霉素处理3天的动物中回收的组织的组织学变化。结果：莫匹罗星治疗导致log10（log R）的负荷降低2.59 cfu/鼻孔（P <0.0001）。以0.8%的剂量给药一次的表皮霉素NI01显示出优异的疗效，导致log R为2.10 cfu/鼻孔（P = 0.0004），与莫匹罗星相当。以0.2%或0.04%剂量每日两次给予表皮霉素NI01，持续3天，对从鼻孔回收的组织负荷无显著影响。观察到轻度至显著的组织学异常，但这些异常被确定为可逆的。结论：单剂量局部表皮霉素NI01与莫匹罗星一样有效，每天两次，持续3天，从棉鼠鼻孔中根除MRSA。这证明了进一步开发用于该适应症的表皮霉素的合理性。
Objectives: To investigate the efficacy of a potent novel antimicrobial protein of mass 6 kDa, epidermicin NI01, for eradicating the nasal burden of MRSA in a cotton rat (Sigmodon hispidus) model. Methods: MRSA strain ATCC 43300 was used to establish a robust colonization of cotton rat nares. This model was used to evaluate the efficacy of topical 0.04% and 0.2% epidermicin NI01, administered twice daily for 3 days consecutively, and topical 0.8% epidermicin NI01 administered once, for reducing nasal MRSA burden. Control groups remained untreated or were administered vehicle only (0.5% hydroxypropylmethylcellulose) or 2% mupirocin twice daily for 3 days. The experiment was terminated at day 5 and MRSA quantitative counts were determined. Tissues recovered from animals treated with 0.2% epidermicin twice daily for 3 days were examined for histological changes. Results: Mupirocin treatment resulted in a reduction in burden of log10 (log R) of 2.59 cfu/nares compared with vehicle (P < 0.0001). Epidermicin NI01 administered once at 0.8% showed excellent efficacy, resulting in a log R of 2.10 cfu/nares (P = 0.0004), which was equivalent to mupirocin. Epidermicin NI01 administered at 0.2% or 0.04% twice daily for 3 days did not have a significant impact on the tissue burden recovered from the nares. Mild to marked histological abnormalities were noted, but these were determined to be reversible. Conclusion: A single dose of topical epidermicin NI01 was as effective as mupirocin administered twice daily for 3 days in eradication of MRSA from the nares of cotton rats. This justifies further development of epidermicin for this indication.