Linezolid and vancomycin decrease the therapeutic effect of methylene blue-photodynamic therapy in a mouse model of MRSA bacterial arthritis.

Linezolid and vancomycin decrease the therapeutic effect of methylene blue-photodynamic therapy in a mouse model of MRSA bacterial arthritis.
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DOI:
10.1111/php.12040
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发表时间:
2013-05
影响因子:
3.3
通讯作者:
Hamblin MR
Hamblin MR
中科院分区:
生物学3区
文献类型:
--
作者:
Tanaka M;Mroz P;Dai T;Huang L;Morimoto Y;Kinoshita M;Yoshihara Y;Shinomiya N;Seki S;Nemoto K;Hamblin MR

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我们以前报道,光动力疗法(PDT)使用关节内亚甲蓝(MB)可用于治疗由生物发光耐甲氧西林金黄色葡萄球菌(MRSA)引起的小鼠关节炎,无论是在治疗还是在预防模式。PDT通过激活趋化因子如炎性细胞因子或趋化因子将中性粒细胞聚集到小鼠膝关节中。在本研究中,我们询问PDT与用于MRSA的抗生素联合使用是否可以在控制感染方面提供额外的益处。我们比较了单独的MB-PDT、单独的利奈唑胺(LZD)或单独的万古霉素(VCM)的全身给药或PDT与LZD或VCM的组合。实时非侵入性成像用于连续跟踪感染的进展。光动力疗法是最有效的,而LZD单独是无效的和VCM单独显示出一些好处。LZD或VCM的加入降低了PDT单独治疗的疗效(P<0.05)。考虑到PDT在这种小鼠模型中刺激中性粒细胞抗菌,而不是主动杀死细菌,我们提出LZD和VCM可能抑制炎症细胞因子的激活而不根除细菌,从而降低PDT的治疗效果。
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 the present 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 non-invasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, while 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.
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