Section Review Anti-infectives: 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 Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CNS), which are resistant to beta-lactams and almost all other first-line antibiotics. They are extensively used in the treatment of severe infections caused by multi-resistant Gram-positive pathogens including enterococci. Enterococcal infections have become a dramatic clinical problem since few antibacterial agents are efficacious against these refractory organisms and increasing resistance is rapidly eliminating the current options. The recent emergence and spread of resistance also to glycopeptides in VanA enterococci poses a serious threat for the future. Some strains of methicillin-resistant CNS have reduced susceptibility to T and occasionally to V. Currently, a major concern is the possibility already demonstrated at laboratory level, that high glycopeptide resistance could be transferred from enterococci to staphylococci. It follows that there is an urgent need for new more potent glycopeptides which combine improved activity against methicillin-resistant staphylococci with excellent activity against highly glycopeptide-resistant enterococci (GRE), or alternative drugs effective against these multi-resistant 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-core structure. Other promising investigational drugs potentially useful for overcoming the serious therapeutic problem of glycopeptide-resistant bacterial infections are also reviewed.