Fidaxomicin (formerly OPT-80) is a narrow-spectrum investigational, nonabsorbed oral agent being developed for the treatment of Clostridium difficile infection (CDI), which is not uncommon among hospitalized patients, resulting in longer hospital stays and increased medical care costs and mortality (2, 6, 7, 9–13, 15, 16). Current CDI therapies are compromised by high recurrence rates and risk of selection for vancomycinresistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) colonization (1, 14). Fidaxomicin, similar to other RNA polymerase inhibitors (8), is active against gram-positive organisms while exhibiting little activity against gram-negative species (7). Furthermore, fidaxomicin clinical trials (phase 2 dose-ranging and phase 3 versus vancomycin for the treatment of CDI) have demonstrated a safety profile (15) similar to that of vancomycin but with a statistically and clinically significant reduction in relapse rate (P 0.004) and improved clinical "global cure" (cure with no relapse; P 0.006) rates compared to vancomycin (2, 9, 12, 13). While several in vitro studies have noted fidaxomicin to be highly active against gram-positive anaerobes, including C. difficile (2, 6, 7), data on its activity against gram-positive aerobic pathogens that can colonize the intestinal tract remain limited. In this study, we evaluated the potency and activity spectrum of fidaxomicin tested against an international collection of common gram-positive isolates recovered from hospitalized patients, including VRE and MRSA.