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 inf ections are Staphylococcus aureus and enterococci. The utility of the tradi tional antibiotics used for nosocomial sepsis, particularly beta-lactam age nts, has been severely compromised by the spread of resistance and there wa s, often, no therapeutic alternative to the glycopeptide antibiotics, vanco mycin and teicoplanin, for empirical land often also the specific) therapy of infections caused by methicillin-resistant S. aureus (MRSA) and Enteroco ccus spp. This reliance on glycopeptides, however, is now also threatened b y 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 con tinents of MESA with reduced glycopeptide-susceptibility (GISA) is of grave concern. New agents are needed to meet these threats and several classes o f compounds are under development. One class is the streptogramins and the combination of quinupristin/dalfopristin (Synercid) is nearing licensing. C linical trials and a compassionate use programme have already shown it to h ave 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.