Mechanisms of daptomycin nonsusceptibility in Staphylococcus aureus

Staphylococcus aureus is a major human pathogen and a model bacterium that has demonstrated rapid emergence of resistance against novel antibiotics shortly after their introduction. Daptomycin is one of the few available intravenous antibiotics used to treat serious bloodstream infections including endocarditis secondary to methicillin-resistant S. aureus (MRSA). Emergence of daptomycin resistance during therapy of MRSA-endocarditis has been documented with this high organism load infection. Daptomycin systemic exposures within a “mutation selection window” have been postulated to contribute to this emergence of daptomycin resistant S. aureus (DRSA) but the underlying mechanisms that drive this phenomenon have not been fully elucidated. Understanding the antibiotic exposure-mutation selection relationship is necessary to define novel strategies to change the existing paradigm.