达托霉素治疗慢性骨髓炎的临床及微生物学经验评述

M. Lozada
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引用次数: 1

摘要

考虑选择达托霉素,一种环脂肽抗生素药物,被批准用于复杂的皮肤和软组织感染,右侧感染性心内膜炎和金黄色葡萄球菌引起的菌血症,但未被批准用于骨感染;达托霉素对革兰氏阳性菌(包括耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素肠球菌(VRE))的杀菌活性,是一种新的作用机制,通过破坏多种细菌的质膜功能而杀死革兰氏阳性菌,而不穿透细胞质[2]。亲脂性达托霉素尾部以寡聚化和通道形成的方式插入细菌细胞膜,导致膜快速去极化和钾离子外排。随后DNA和RNA合成、毒素产生和蛋白质合成被阻止,导致细菌死亡而不破坏细胞壁,这在炎症反应相关的抗微生物药物使用产生细胞裂解的疾病中具有进一步的优势[3-5],此外,达托霉素的体外药效已被证明可治疗耐万古霉素金黄色葡萄球菌(VRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)。已在体外描述的达托霉素与氨基糖苷类(庆大霉素)、氧苄西林、其他倍他内酰胺类、大环内酯类和利福平的协同作用,对生物膜疾病感染的治疗非常有价值,这种抗生物膜活性和减少利福平耐药的出现具有很大的价值。达托霉素与几种抗菌药物联合使用未观察到拮抗相互作用,仅报道了加性、协同效应或无差异作用。另一个相关的方面是联合或单独使用达托霉素的部分抗生物膜活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comments of Clinical and Microbiological Experience with Daptomycin in Chronic Osteomyelitis Treatment
The consideration for select daptomycin, a cyclic lipopeptide antibiotic drug, approved for complicated skin and soft tissue infections, right-sided infective endocarditis and bacteraemia due to Staphylococcus aureus [1], but not approved for use in bone infection; to treat a complex pathology like CO, comes from differents factors like daptomycin’s bactericidal activity against Gram-positive bacteria, including Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococci (VRE), a novel mechanism of action that kills Grampositive bacteria by the disruption of multiple bacterial plasma membrane functions, without penetrating the cytoplasm [2]. Insertion of the lipophilic daptomycin tail into the bacterial cell membrane with oligomerization and channel formation causes rapid membrane depolarization and a potassium ion efflux. Arrest of DNA & RNA synthesis, toxin production, and protein synthesis follows, resulting in bacterial death without lysis of the cell wall, which gives a further advantage in diseases where inflammatory response associated counter antimicrobial use producing cell lysis [3-5], in addition, the in vitro potency of daptomycin has been demonstrated against Vancomycin resistant S. aureus (VRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS). The synergic effect for daptomycin that has been described in vitro with aminoglycosides (gentamicin), oxacillin, other betalactamics, macrolides and rifampicin, is very valuable to biofilm disease infections treatment, and this antibiofilm activity and reduction of the rifampicin resistance appearance makes a great value. Not antagonism interactions was observed with daptomycin use in combination with several antimicrobial agents, only additive, synergistic effect or indifference were reported. Another relevant aspect is the partial anti-biofilm activity of daptomycin, combined or alone.
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