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We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin\u00ae in a mouse model of methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design\/Materials and Methods<\/jats:title><jats:p>The present study used an intra\u2010articular injection of Photofrin\u00ae and optimized the light dosimetry in order to maximize bacterial killing and minimize killing of host neutrophils. MRSA (5\u2009\u00d7\u200910<jats:sup>7<\/jats:sup>\u2009CFU) was injected into the mouse knee followed 3 days later by 1\u2009\u00b5g of Photofrin\u00ae and 635\u2010nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1\u20133, 5, and 7 days after PDT to determine MRSA colony\u2010forming units (CFU), neutrophil numbers, and levels of cytokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20\u2009J\u2009cm<jats:sup>\u22122<\/jats:sup>, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein\u20102, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20\u2009J\u2009cm<jats:sup>\u22122<\/jats:sup> compared to fluences of 5 or 70\u2009J\u2009cm<jats:sup>\u22122<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense. Lasers Surg. Med. 43:221\u2013229, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.21037","type":"journal-article","created":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T15:21:10Z","timestamp":1300202470000},"page":"221-229","source":"Crossref","is-referenced-by-count":39,"title":["Photodynamic therapy using intra\u2010articular photofrin for murine MRSA arthritis: Biphasic light dose response for neutrophil\u2010mediated antibacterial 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