For example, in a multicenter, prospective, observational investi- gation involving >1000 consecutive patients with definite IE from >20 countries, S aureus was the most common cause of PVE (25.8% of 214 cases), whereas 64 cases of NVE (8%) resulted from CoNS.136 In addition, the prevalence of CoNS NVE appears to be increasing.137 Thus, it is important to con- sider both pathogen groups when a patient with suspected IE has a preliminary blood culture that suggests staphylococci by Gram stain interpretation. S aureus S aureus is the most common cause of IE in much of the devel- Data from >70 million hospitalizations in the United States suggest that rates of S aureus IE have increased significantly relative to other causes of IE.3 This increase is primarily a consequence of healthcare contact (eg, intra- vascular catheters, surgical wounds, indwelling prosthetic and is especially prevalent in North Increasing rates of oxacillin-resistant S aureus or MRSA isolates in both hospital and community settings and the recovery of clinical S aureus isolates both partially resistant to vancomycin have complicated the treatment of S aureus IE. 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). 