Efficacy of current agents used in the treatment of Gram-positive infections and the consequences of resistance

The proportion of pathogens causing hospital-onset infections that are resistant to antimicrobial agents continues to increase worldwide. Inadequate antimicrobial therapy is an important factor in the emergence of resistance and is associated with increased mortality. In the USA in 2000, the National Nosocomial Infections Surveillance system reported that >50% of Staphylococcus aureus isolates collected from intensive care units were resistant to methicillin (MRSA). The emergence of community-acquired MRSA is a new concern. MRSA are associated with adverse clinical outcomes and increased hospital costs. The increasing prevalence of MRSA contributes to the use of glycopeptides; however, isolates with intermediate and full resistance to vancomycin and teicoplanin are now being reported. Newer agents, such as the oxazolidinone linezolid, are effective in the treatment of serious Gram-positive infections; however, linezolid-resistant isolates of Enterococcus faecium, Enterococcus faecalis and S. aureus have been reported. Therefore, there is an unmet clinical need for new agents with activity against Gram-positive pathogens. Daptomycin, a lipopeptide with a novel mode of action, was recently approved for the treatment of skin and soft tissue infections in the USA. The two case studies presented herein detail experience with the use of daptomycin in the USA.