The nosocomial infection rate has increased dramatically due to emergence of antibiotic resistant bacterial strains such as methicillin resistant Staphylococcus aureus (MRSA). The primary anatomical site of MRSA colonization is the anterior nares, and this reservoir represents a primary vector of transmission from non-infected carriers to susceptible individuals. Antimicrobial photodynamic therapy (aPDT) has been used successfully for topical disinfection in the oral cavity. The aim of this study was to evaluate the utility of aPDT for nasal MRSA decolonization at the preclinical and clinical level. The nasal aPDT system consists of a 670 nm diode laser fibre-optically coupled to a disposable light diffusing tip, used to activate a methylene blue based photosensitizer formulation. Preclinical testing was done both in a custom nasal reservoir model and on human skin cultures colonized on the epithelial surface with MRSA. Human clinical testing was performed by clinicians in regions in which the system is approved by the regulatory authority. In vitro testing demonstrated that aPDT eradicated planktonic MRSA in an energy and photosensitizer concentration dependent manner. Furthermore, aPDT eliminated sustained colonization of MRSA on cultured human epithelial surfaces, an effect that was sustained over multiple days post-treatment. In preliminary human testing, aPDT eradicated MRSA completely from the nose with total treatment times <10 minutes. aPDT is effective against MRSA when used topically in the nose. Energy dose and photosensitizer parameters have been optimized for the nasal environment. Controlled clinical studies are currently underway to further evaluate safety and efficacy.© (2009) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.