THE MECHANISM OF RESISTANCE TO GLYCOPEPTI DE ANTIBIOTICS AS THE BASISFOR THE DEVELOPMENT OF NOVEL DERIVATIVES CAPABLE OF OVERCOMING THE RESISTANCE

The data on the genetic and biochemical bases of bacterial resistance to antibiotics of the vancomycin-ristocetin group are summarized. Spec ial emphasis is placed on the mechanism of resistance associated with target modification and on molecular interactions occurring upon conta ct of glycopeptides with normal and modified targets. The prospects fo r developing new derivatives active against resistant bacteria are dis cussed. The most rational approach to the chemical transformation of g lycopeptides involves the modification of the internal ''binding pocke t'' and the peripheral regions of the molecule that participate in the stabilization of the antibiotic-target complex. Novel semisynthetic d rugs of this group active against glycopeptide-resistant enterococci a re described.