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Daptomycin (4 mg/kg IV q24h for skin and skin structure infections; 6–10 mg/kg IV q24h for bloodstream infections) is a cyclic lipopeptide. The drug exhibits rapid bactericidal activity against a wide variety of gram-positive bacteria, including enterococci, staphylococci, and streptococci. Daptomycin is FDA approved for treatment of complicated skin and skin structure infections as well as S. aureus bacteremia and right-sided endocarditis. The drug should not be used to treat lung infections as activity is decreased in the presence of pulmonary surfactant. Nonsusceptibility to daptomycin can develop, making it imperative that susceptibility of isolates be verified.