Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells
Bactericidal action of daptomycin against stationary-phase and nondividing Staphylococcus aureus cells
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DOI：
10.1128/aac.00824-07
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发表时间：
2007-12-01
影响因子：
4.9
通讯作者：
Silverman, Jared A.
中科院分区：
文献类型：
--
作者：
Mascio, Carmela T. M.;Alder, Jeff D.;Silverman, Jared A.
大多数具有杀菌活性的抗生素要求细菌积极分裂以产生快速杀伤。然而，在许多感染中，如心内膜炎、假体关节感染和植入导管感染，细菌分裂缓慢或根本不分裂。达托霉素是一种脂肽类抗生素，具有独特的作用机制，可靶向革兰氏阳性生物的细胞质膜，包括金黄色葡萄球菌。达托霉素对呈指数增长的细菌具有快速杀菌作用（60分钟内减少3对数）。本研究的目的是确定达托霉素是否对非分裂金黄色葡萄球菌具有杀菌作用，并量化其杀菌活性的程度。在固定相（10(10)CFU/ml）的高接种量甲氧西林敏感金黄色葡萄球菌培养物中，达托霉素显示出浓度依赖性的杀菌活性，需要32 μ g/ml才能达到3对数的降低。在一项比较几种抗生素100 μ g/ml的研究中，达托霉素显示出比萘西林、环丙沙星、庆大霉素和万古霉素更快的杀菌活性。在用代谢抑制剂羰基氰化物间氯苯肼或红霉素停止细菌细胞生长的实验中，达托霉素（10 μ g/ml）在2小时内达到了杀菌终点（减少3对数）。相比之下，环丙沙星（10 μ g/ml）没有产生杀菌活性。达托霉素（2 μ g/ml）对冷阻金黄色葡萄球菌仍有杀菌作用，但对环丙沙星和萘西林的作用有保护作用。本文提供的数据表明，与其他种类的抗生素相比，达托霉素的杀菌活性不需要细胞分裂或活跃的代谢，这很可能是其直接作用于细菌膜的结果。
Most antibiotics with bactericidal activity require that the bacteria be actively dividing to produce rapid killing. However, in many infections, such as endocarditis, prosthetic joint infections, and infected embedded catheters, the bacteria divide slowly or not at all. Daptomycin is a lipopeptide antibiotic with a distinct mechanism of action that targets the cytoplasmic membrane of gram-positive organisms, including Staphylococcus aureus. Daptomycin is rapidly bactericidal against exponentially growing bacteria (a 3-log reduction in 60 min). The objectives of this study were to determine if daptomycin is bactericidal against nondividing S. aureus and to quantify the extent of the bactericidal activity. In high-inoculum methicillin-sensitive S. aureus cultures in stationary phase (10(10) CFU/ml), daptomycin displayed concentration-dependent bactericidal activity, requiring 32 mu g/ml to achieve a 3-log reduction. In a study comparing several antibiotics at 100 mu g/ml, daptomycin demonstrated faster bactericidal activity than nafcillin, ciprofloxacin, gentamicin, and vancomycin. In experiments where bacterial cell growth was halted by the metabolic inhibitor carbonyl cyanide m-chlorophenylhydrazone or erythromycin, daptomycin (10 mu g/ml) achieved the bactericidal end point (a 3-log reduction) within 2 h. In contrast, ciprofloxacin (10 mu g/ml) did not produce bactericidal activity. Daptomycin (2 mu g/ml) remained bactericidal against cold-arrested S. aureus, which was protected from the actions of ciprofloxacin and nafcillin. The data presented here suggest that, in contrast to that of other classes of antibiotics, the bactericidal activity of daptomycin does not require cell division or active metabolism, most likely as a consequence of its direct action on the bacterial membrane.