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Linezolid and Vancomycin Decrease the Therapeutic Effect of Methylene Blue-Photodynamic therapy in a Mouse Model of MRSA Bacterial Arthritis

Authors

  • Masamitsu Tanaka,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
    3. Department of Orthopedic Surgery, National Defense Medical College, Saitama, 359-8513, Japan
    4. Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan
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  • Pawel Mroz,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
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  • Tianhong Dai,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
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  • Liyi Huang,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
    2. Department of Dermatology, Harvard Medical School, Boston, MA
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  • Yuji Morimoto,

    Corresponding author
    1. Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan
    • Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
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  • Manabu Kinoshita,

    1. Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan
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  • Yasuo Yoshihara,

    1. Department of Orthopedic Surgery, National Defense Medical College, Saitama, 359-8513, Japan
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  • Nariyoshi Shinomiya,

    1. Department of Integrated Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan
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  • Shuhji Seki,

    1. Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan
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  • Koichi Nemoto,

    1. Department of Orthopedic Surgery, National Defense Medical College, Saitama, 359-8513, Japan
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  • Michael R. Hamblin

    Corresponding author
    1. Department of Dermatology, Harvard Medical School, Boston, MA
    2. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA
    • Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA
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Corresponding authors email: moyan@ndmc.ac.jp (Yuji Morimoto); hamblin@helix.mgh.harvard.edu(Michael R. Hamblin)

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 (< 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.

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