Which antibiotic for resistant Gram-positives, and why?

Increasing resistance in Gram-positive pathogens, particularly Staphylococcus aureus, and enterococcus, has become a major clinical problem, particularly in the hospital environment, causing significant morbidity and mortality in both healthy hosts and in those with underlying comorbidities. Increased resistance drives the use of empiric therapy with less well-studied and potentially more toxic agents. Resistance mechanisms for currently recommended agents are discussed, with options for therapy of resistant pathogens. For any new agent used, resistance is likely to develop, which underscores the concept that both antibiotics and antimicrobial resistance are ancient, and only by prudent use of antimicrobial agents and effective infection control measures when resistance arises, will effective agents be available to treat Gram-positive pathogens in the future.