Nasal decolonization has a proven effect on the prevention of severe Staphylococcus aureus infections and the control of methicillin-resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization. LTX-109 is a broad-spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study, persistent nasal MRSA and methicillin-sensitive S. aureus (MSSA) carriers were treated for 3 days with vehicle or with 1%, 2%, or 5% LTX-109. A significant effect on nasal decolonization was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P ≤ 0.0012 by Dunnett's test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low, with a maximum concentration of drug in plasma (Cmax) at 1 to 2 h postdosing (3.72 to 11.7 ng/ml). One week after treatment initiation, LTX-109 was not detectable in any subject. Intranasal treatment of S. aureus with LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has potential as a new and effective antimicrobial agent with a low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. (This study has been registered at ClinicalTrials.gov under registration no. NCT01158235.).

中文翻译：

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LTX-109 是一种新型药物，用于对耐甲氧西林和敏感的金黄色葡萄球菌进行鼻腔去定植。

经证实，鼻腔非定植在预防严重的金黄色葡萄球菌感染和控制耐甲氧西林金黄色葡萄球菌 (MRSA) 方面具有显着效果。然而，抗生素耐药率的上升凸显了鼻腔非定植对新物质的需求。LTX-109 是一种广谱、速效杀菌抗菌药物，用于局部治疗，可导致膜破裂和细胞裂解。这种作用机制与交叉抗药性无关，并且产生抗药性的倾向较低。在本研究中，持续鼻腔 MRSA 和甲氧西林敏感的金黄色葡萄球菌 (MSSA) 携带者用载体或 1%、2% 或 5% LTX-109 治疗 3 天。与媒介物相比，用 2% 或 5% LTX-109 治疗的受试者在接受 LTX-109 治疗 2 天后，已经观察到对鼻腔去定植的显着影响（P ≤ 0.0012 通过 Dunnett 检验）。在 9 周的随访期间没有发现安全问题。在鼻腔中观察到最小的可逆上皮病变。全身暴露量非常低，给药后 1 至 2 小时的血浆药物浓度 (Cmax) 最高（3.72 至 11.7 ng/ml）。治疗开始一周后，在任何受试者中均未检测到 LTX-109。使用 LTX-109 对金黄色葡萄球菌进行鼻内治疗是安全的，并且在一天的治疗后已经减少了细菌负荷。因此，LTX-109 具有作为一种新的有效抗菌剂的潜力，具有低耐药性发展倾向，可以预防住院期间 MSSA/MRSA 的感染。（本研究已在 ClinicalTrials.gov 注册，注册号为 NCT01158235。）。