Silverman Jared A, Mortin Lawrence I, Vanpraagh Andrew D G, Li Tongchuan, Alder Jeff
Cubist Pharmaceuticals, Lexington, Massachusetts 02421, USA.
J Infect Dis. 2005 Jun 15;191(12):2149-52. doi: 10.1086/430352. Epub 2005 May 5.
The lipopeptide daptomycin has been approved for use in skin and skin-structure infections but has failed to meet statistical noninferiority criteria in a clinical trial for severe community-acquired pneumonia. Daptomycin exhibited an unusual pattern of activity in pulmonary animal models: efficacy in Staphylococcus aureus hematogenous pneumonia and inhalation anthrax but no activity against Streptococcus pneumoniae in simple bronchial-alveolar pneumonia. Daptomycin was shown to interact in vitro with pulmonary surfactant, resulting in inhibition of antibacterial activity. This effect was specific to daptomycin and consistent with its known mechanism of action. This represents the first example of organ-specific inhibition of an antibiotic.
脂肽类药物达托霉素已被批准用于治疗皮肤及皮肤结构感染，但在一项针对严重社区获得性肺炎的临床试验中未能达到统计学非劣效性标准。达托霉素在肺部动物模型中呈现出一种不同寻常的活性模式：对金黄色葡萄球菌血源性肺炎和吸入性炭疽有效，但对单纯支气管肺泡肺炎中的肺炎链球菌无活性。研究表明，达托霉素在体外与肺表面活性物质相互作用，从而抑制其抗菌活性。这种效应是达托霉素所特有的，与其已知的作用机制相符。这是抗生素出现器官特异性抑制的首个实例。
