Biomedical Sciences Research Complex, School of Biology, University of St Andrews, North Haugh, Fife KY16 9ST, UK.
J Antimicrob Chemother. 2013 Nov;68(11):2569-75. doi: 10.1093/jac/dkt243. Epub 2013 Jun 25.
To evaluate the in vivo effectiveness of a combination treatment containing ranalexin (a natural antimicrobial peptide) and lysostaphin (an antistaphylococcal endopeptidase) for reducing nasal burden of methicillin-resistant Staphylococcus aureus (MRSA).
The community-acquired MRSA strain S. aureus NRS384 (USA300-0114) was used in the present study because it is commonly isolated from human nares and it established consistent and reproducible colonization of cotton rat nares. This model was used to evaluate the efficacy of ranalexin/lysostaphin gels (0.1%-1% w/v; administered intranasally once or once per day for 3 consecutive days) for reducing nasal MRSA burden. Control animals were administered vehicle gel only (0.5% hydroxypropyl methylcellulose) or 2% mupirocin, which is used clinically for nasal decolonization of MRSA. Nasal MRSA burden was assessed at 192 h post-inoculation, which was at least 72 h after the final treatment had been administered. An additional study assessed the efficacy of 0.1% ranalexin/lysostaphin against a mupirocin-resistant MRSA strain (MUP20), which had been selected by serial passage of S. aureus NRS384 through subinhibitory concentrations of mupirocin.
Gels containing 0.1% ranalexin/lysostaphin consistently reduced median nasal burden of MRSA to an extent similar to or greater than 2% mupirocin. Treatment with 0.1% ranalexin/lysostaphin was also effective against the MUP20 strain. There was evidence for only minimal irritancy in cotton rat nares administered three doses of 0.1% ranalexin/lysostaphin, suggesting that this agent is suitable for short-course therapy such as is employed currently for nasal decolonization with mupirocin.
Ranalexin/lysostaphin could serve as an alternative to mupirocin for nasal decolonization of MRSA.
评估包含ranalexin（一种天然抗菌肽）和lysostaphin（一种抗葡萄球菌内肽酶）的联合治疗方案减少耐甲氧西林金黄色葡萄球菌（MRSA）鼻腔负担的体内疗效。
本研究使用社区获得性 MRSA 菌株金黄色葡萄球菌 NRS384（USA300-0114），因为它通常从人鼻腔中分离出来，并且可以在棉鼠鼻腔中建立一致且可重复的定植。该模型用于评估 ranalexin/lysostaphin 凝胶（0.1%-1%w/v；鼻内给药一次或连续 3 天每天一次）减少鼻腔 MRSA 负担的疗效。对照动物仅给予载体凝胶（0.5%羟丙基甲基纤维素）或 2%莫匹罗星，后者临床上用于 MRSA 的鼻腔去定植。鼻腔 MRSA 负担在接种后 192 小时评估，这至少是最后一次治疗后 72 小时。另一项研究评估了 0.1%ranalexin/lysostaphin 对莫匹罗星耐药 MRSA 菌株（MUP20）的疗效，该菌株是通过金黄色葡萄球菌 NRS384 在亚抑菌浓度的莫匹罗星中连续传代选择的。
含有 0.1%ranalexin/lysostaphin 的凝胶一致地将 MRSA 的中位鼻腔负担降低到与 2%莫匹罗星相似或更大的程度。用 0.1%ranalexin/lysostaphin 治疗也对 MUP20 菌株有效。在接受三剂 0.1%ranalexin/lysostaphin 的棉鼠鼻腔中仅存在轻微刺激的证据，表明该药物适合于短程治疗，例如目前用于莫匹罗星的鼻腔去定植。
ranalexin/lysostaphin 可作为莫匹罗星的替代物用于 MRSA 的鼻腔去定植。
