Recent developments in reversing glycopeptide-resistant pathogens

Review with 199 refs. Recent studies addressing vancomycin-resistance phenomena are surveyed. Besides leading semi-synthetic glycopeptides: BI-397 and LY 333328, other new synthetic derivs. are also presented. Rational design based on the known mode of action is seen in recent research from both industrial and academic groups. Thus, Biosearch Italia SpA worked on new synthetic glycopeptides with a modified binding pocket in order to find drugs active against both vancomycin-sensitive and -resistant strains. Eli Lilly & Co. and research groups at Stanford, Cambridge and Harvard synthesized covalently linked dimers in order to copy the dimerization and membrane anchoring effects. Both directions proved to be rewarding and some interesting compds. with potent in vitro activity against vancomycin-resistant enterococci (VRE) were found from these investigations. A new mechanistic proposal that can account for the bioactivity of LY 333328 against VRE was summarized. Research on new agents with modes of action different to that of glycopeptide antibiotics have also been successful and recent investigations related to RP-59500, SCH-27899 and U-100766 are presented. [on SciFinder (R)]