Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice
Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice
复制标题
DOI：
10.1128/aac.00027-09
复制
发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Hamblin, Michael R.
中科院分区：
文献类型：
--
作者：
Dai, Tianhong;Tegos, George P.;Hamblin, Michael R.
多重耐药鲍曼不动杆菌感染是一个日益严重的问题，特别是在中东冲突中受伤的军事人员遭受的创伤和烧伤。传统抗生素的有效治疗可能非常困难，新的抗菌方法正在研究中。抗菌剂的替代品之一可能是无毒光敏剂（PS）和可见光的组合，称为光动力疗法（PDT）。我们报告了一种新的小鼠全层热烧伤模型的建立，该模型感染了一种伊拉克临床分离的A。鲍曼不动杆菌及其PDT治疗，方法是局部应用由二氢卟酚（e6）与聚乙烯亚胺共价结合产生的PS，然后用红光照射烧伤表面。第10条（8）A。将鲍曼不动杆菌细胞接种到剃毛的雌性BALB/c小鼠的背部表面上进行的10秒烧伤的表面上，导致慢性感染，平均持续22天，并且其特征在于显著稳定的细菌生物发光。在施用细菌后不久的第0天进行的PDT以光致发光依赖的方式给出了超过3log单位的细菌发光损失，而在第1天和第2天进行的PDT给出了约1.7-log减少。应用溶解在10%或20%二甲基亚砜中的PS，在没有光的情况下，小鼠烧伤的细菌发光仅适度减少。在治疗的烧伤中观察到一些细菌再生长，但通常是适度的。同时发现PDT并不导致伤口愈合的抑制。光动力疗法可能是治疗耐多药局限性铜绿假单胞菌的一种有效的新方法。鲍曼不动杆菌感染。
Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10(8) A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.