Novel streptogramin antibiotics

作者：Giovanni Bonfiglio, Pio Maria Furneri · 发表于：Expert Opinion on Investigational Drugs · 年份：2001 · DOI：10.1517/13543784.10.2.185 · 被引用次数：52 · 研究领域：Antimicrobial Resistance in Staphylococcus、Antibiotics Pharmacokinetics and Efficacy、Antifungal resistance and susceptibility

Streptogramins represent a unique class of antibiotics remarkable for their antibacterial activity and their unique mechanism of action. These antibiotics are produced naturally as secondary metabolites by a number of Streptomyces species and have been classified into two main groups. They consist of at least two structurally unrelated compounds, group A or M (macrolactones) and group B or S (cyclic hexadepsipeptides). Both groups bind bacterial ribosomes and inhibit protein synthesis at the elongation step and they act synergistically in vitro against many microorganisms. Streptogramins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible. The pharmacokinetic parameters of group A and B streptogramins in blood are similar. The major gap, limiting the therapeutic use of the natural compounds, was represented by the lack dissolution in water. The synthesis of water-soluble derivatives of pristinamycin I(A) and II(B) has allowed the development of injectable, first represented by quinupristin/dalfopristin (Synercid) and oral formulations, represented by RPR-106972, streptogramins with fixed compositions. Streptogramins have demonstrated activity against Gram-positive microorganisms in vitro and in vivo, including those with multi-drug resistance. Moreover, the absence of cross-resistance to macrolides in many of these microorganisms and the rarity of cross-resistance betwe...