Chemotherapy for gram-positive nosocomial sepsis

Over recent years gram-positive bacterial pathogens have become dominant in many forms of nosocomial infections. The principal pathogens in severe infections are Staphylococcus aureus and enterococci. The utility of the traditional antibiotics used for nosocomial sepsis, particularly beta-lactam agents, has been severely compromised by the spread of resistance and there was, often, no therapeutic alternative to the glycopeptide antibiotics, vancomycin and teicoplanin, for empirical (and often also the specific) therapy of infections caused by methicillin-resistant S. aureus (MRSA) and Enterococcus spp. This reliance on glycopeptides, however, is now also threatened by acquired resistance. Vancomycin-resistant enterococci (VRE), particularly E. faecium, have become a therapeutic problem in many European cities and are now endemic in some hospital wards. The recent reports from several continents of MRSA with reduced glycopeptide-susceptibility (GISA) is of grave concern. New agents are needed to meet these threats and several classes of compounds are under development. One class is the streptogramins and the combination of quinupristin/dalfopristin (Synercid) is nearing licensing. Clinical trials and a compassionate use programme have already shown it to have considerable promise for the treatment of the most problematic forms of gram-positive nosocomial sepsis, including MRSA and vancomycin-resistant E. faecium infections that had failed therapy with other antibiotics.