NEW APPROACHES TO THE TREATMENT OF VANCOMYCIN-RESISTANT BACTERIAL-INFECTIONS

Commercially available glycopeptides Vancomycin (V) and Teicoplanin (T ) are drugs of choice for the treatment of methicillin-resistant Staph ylococcus aureus (MRSA) and coagulase-negative staphylococci (CNS), wh ich are resistant to beta-lactams and almost all other first-line anti biotics. They are extensively used in the treatment of severe infectio ns caused by multi-resistant Gram-positive pathogens including enteroc occi. Enterococcal infections have become a dramatic clinical problem since few antibacterial agents are efficacious against these refractor y organisms and increasing resistance is rapidly eliminating the curre nt options. The recent emergence and spread of resistance also to glyc opeptides in VanA enterococci poses a serious threat for the future. S ome strains of methicillin-resistant CNS have reduced susceptibility t o T and occasionally to V. Currently, a major concern is the possibili ty already demonstrated at laboratory level, that high glycopeptide re sistance could be transferred from enterococci to staphylococci. It fo llows that there is an urgent need for new more potent glycopeptides w hich combine improved activity against methicillin-resistant staphyloc occi with excel ie nt activity against highly glycopeptide-resistant e nterococci (GRE), or alternative drugs effective against these multi-r esistant bacteria. This article describes the most recent findings and results achieved in this field with new glycopeptide derivatives and novel approaches based on modifications of the natural glycopeptide-co re structure. Other promising investigational drugs potentially useful for overcoming the serious therapeutic problem of glycopeptide-resist ant bacterial infections are also reviewed.