title: Linezolid and vancomycin decrease the therapeutic effect of methylene blue-photodynamic therapy in a mouse model of MRSA bacterial arthritis.
abstract: We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P < 0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT.
authors: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Masamitsu
authors: M
authors: Tanaka
authors: Pawel
authors: P
authors: Mroz
authors: Tianhong
authors: T
authors: Dai
authors: Liyi
authors: L
authors: Huang
authors: Yuji
authors: Y
authors: Morimoto
authors: Manabu
authors: M
authors: Kinoshita
authors: Yasuo
authors: Y
authors: Yoshihara
authors: Nariyoshi
authors: N
authors: Shinomiya
authors: Shuhji
authors: S
authors: Seki
authors: Koichi
authors: K
authors: Nemoto
authors: Michael R
authors: MR
authors: Hamblin
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D007270:Injections, Intra-Articular; D017746:Joint Capsule / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008027:Light; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008751:Methylene Blue / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D023303:Oxazolidinones / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D016207:Cytokines; D023303:Oxazolidinones; D017319:Photosensitizing Agents; D014640:Vancomycin; D000069349:Linezolid; D008751:Methylene Blue