Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711, USA.
J Antimicrob Chemother. 2021 May 12;76(6):1532-1538. doi: 10.1093/jac/dkab040.
To evaluate the efficacy of a novel lantibiotic, CMB001, against MRSA biofilms in vitro and in an in vivo experimental model of bacterial infection.
Antibacterial activity of CMB001 was measured in vitro after its exposure to whole blood or to platelet-poor plasma. In vitro efficacy of CMB001 against a Staphylococcus aureus biofilm was studied using scanning electron microscopy. The maximum tolerable dose in mice was determined and a preliminary pharmacokinetic analysis for CMB001 was performed in mice. In vivo efficacy was evaluated in a neutropenic mouse thigh model of infection.
CMB001 maintained its antibacterial activity in the presence of blood or plasma for up to 24 h at 37°C. CMB001 efficiently killed S. aureus within the biofilm by causing significant damage to the bacterial cell wall. The maximum tolerable dose in mice was established to be 10 mg/kg and could be increased to 30 mg/kg in mice pretreated with antihistamines. In neutropenic mice infected with MRSA, treatment with CMB001 reduced the bacterial burden with an efficacy equivalent to that of vancomycin.
CMB001 offers potential as an alternative treatment option to combat MRSA. It will be of interest to evaluate the in vivo efficacy of CMB001 against infections caused by other pathogens, including Clostridioides difficile and Acinetobacter baumannii, and to expand its pharmacokinetic/pharmacodynamic parameters and safety profile.
评估新型类细菌素 CMB001 对耐甲氧西林金黄色葡萄球菌（MRSA）生物膜的体外和体内感染实验模型中的疗效。
在暴露于全血或血小板贫乏血浆后，测量 CMB001 的体外抗菌活性。使用扫描电子显微镜研究 CMB001 对金黄色葡萄球菌生物膜的体外疗效。测定小鼠的最大耐受剂量，并在小鼠中进行 CMB001 的初步药代动力学分析。在中性粒细胞减少症小鼠大腿感染模型中评估体内疗效。
CMB001 在 37°C 下的血液或血浆中保持其抗菌活性长达 24 小时。CMB001 通过对细菌细胞壁造成严重损伤，有效地杀死生物膜内的金黄色葡萄球菌。在未用抗组胺药预处理的小鼠中，建立了最大耐受剂量为 10mg/kg，在预先用抗组胺药预处理的小鼠中，最大耐受剂量可增加至 30mg/kg。在感染耐甲氧西林金黄色葡萄球菌的中性粒细胞减少症小鼠中，CMB001 治疗可降低细菌负荷，疗效与万古霉素相当。
CMB001 作为治疗耐甲氧西林金黄色葡萄球菌的替代治疗选择具有潜力。评估 CMB001 对其他病原体（包括艰难梭菌和鲍曼不动杆菌）引起的感染的体内疗效，并扩大其药代动力学/药效学参数和安全性概况将是很有意义的。
