Fernandes Prabhavathi
Cempra Incorporated, Chapel Hill, North Carolina 27517.
Cold Spring Harb Perspect Med. 2016 Jan 4;6(1):a025437. doi: 10.1101/cshperspect.a025437.
Fusidic acid is an oral antistaphylococcal antibiotic that has been used in Europe for more than 40 years to treat skin infections as well as chronic bone and joint infections. It is a steroidal antibiotic and the only marketed member of the fusidane class. Fusidic acid inhibits protein synthesis by binding EF-G-GDP, which results in the inhibition of both peptide translocation and ribosome disassembly. It has a novel structure and novel mode of action and, therefore, there is little cross-resistance with other known antibiotics. Many mutations can occur in the FusA gene that codes for EF-G, and some of these mutations can result in high-level resistance (minimum inhibitory concentration [MIC] > 64 mg/L), whereas others result in biologically unfit staphylococci that require compensatory mutations to survive. Low-level resistance (<8 mg/L) is more common and is mediated by fusB, fusC, and fusD genes that code for small proteins that protect EF-G-GDP from binding fusidic acid. The genes for these proteins are spread by plasmids and can be selected mostly by topical antibiotic use. Reports of resistance have led to combination use of fusidic acid with rifampin, which is superseded by the development of a new dosing regimen for fusidic acid that can be used in monotherapy. It consists of a front-loading dose to decrease the potential for resistance development followed by a maintenance dose. This dosing regimen is now being used in clinical trials in the United States for skin and refractory bone and joint infections.
夫西地酸是一种口服抗葡萄球菌抗生素，在欧洲已使用40多年，用于治疗皮肤感染以及慢性骨和关节感染。它是一种甾体抗生素，也是夫西地烷类中唯一上市的成员。夫西地酸通过结合EF-G-GDP抑制蛋白质合成，从而抑制肽链移位和核糖体解体。它具有新颖的结构和作用方式，因此与其他已知抗生素几乎没有交叉耐药性。编码EF-G的FusA基因可发生许多突变，其中一些突变可导致高水平耐药（最低抑菌浓度[MIC]>64mg/L），而其他突变则导致生物学上不适应的葡萄球菌，需要补偿性突变才能存活。低水平耐药（<8mg/L）更为常见，由fusB、fusC和fusD基因介导，这些基因编码的小蛋白可保护EF-G-GDP不与夫西地酸结合。这些蛋白的基因通过质粒传播，主要可通过局部使用抗生素来选择。耐药性报告导致夫西地酸与利福平联合使用，但一种可用于单药治疗的夫西地酸新给药方案的开发取代了这种联合使用方式。该方案包括一个负荷剂量以降低耐药性产生的可能性，随后是维持剂量。这种给药方案目前正在美国用于皮肤及难治性骨和关节感染的临床试验。
