An increasing body of evidence suggests an association between high (but still susceptible on the basis of the Clinical and Laboratory Standards Institute definition) vancomycin MICs in S aureus and worse clinical outcome in both MRSA infections treated with vancomycin140 and MRSA bacteremia treated with antistaphylococcal peni- Importantly, this association between higher vanco- mycin MIC in infecting MSSA and worse clinical outcomes among patients treated with antistaphylococcal penicillins (not vancomycin) was externally validated in a large cohort of patients with MSSA IE.142 These data suggest that host- or pathogen-specific factors, rather than higher MICs of the infecting pathogen to vancomycin, contribute to the poor out- comes in these patients (because the latter patients were not treated with a glycopeptide). In non-IDUs, S aureus IE involves primarily the left side of the heart and is associated with mortality rates ranging from 25% to 40%. S aureus IE in IDUs often involves the tricuspid valve. Cure rates for right-sided S aureus IE in IDUs are high (>85%) and may be achieved with relatively short courses of either parenteral or oral treatment (2 4 weeks; see below). Complicated IE manifested, for example, by deep tis- sue abscesses or osteoarticular infection may require more prolonged therapy. Coagulase-Negative Staphylococci As noted above, in addition to their importance in PVE, CoNS now cause a significant but relatively small proportion of NVE Risk factors for CoNS IE are similar to those for S aureus and include typical risk factors associated with exten- sive healthcare contact. Of interest, data suggest that the over- all outcomes for patients with CoNS IE and S aureus IE are Most CoNS are resistant to methicillin. These resis- tant organisms are particularly prominent among patients with healthcare-associated staphylococcal IE. 