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碘卡地醇在体外和体内对细菌性伤口生物膜均具有卓越的疗效。

Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo.

作者信息

Fitzgerald Daniel J, Renick Paul J, Forrest Emma C, Tetens Shannon P, Earnest David N, McMillan Jillian, Kiedaisch Brett M, Shi Lei, Roche Eric D

机构信息

Research & Development, Advanced Wound Development, Smith & Nephew, Heslington, York, United Kingdom.

Research & Development, Advanced Wound Development, Smith & Nephew, Fort Worth, Texas.

出版信息

Wound Repair Regen. 2017 Jan;25(1):13-24. doi: 10.1111/wrr.12497. Epub 2016 Dec 5.

Abstract

Examination of clinical samples indicates bacterial biofilms are present in the majority of chronic wounds, and substantial evidence suggests biofilms contribute significantly to delayed healing. Bacteria in biofilms are highly tolerant of antimicrobials, and little data exist to guide the choice of anti-biofilm wound therapy. Cadexomer iodine (CI) was recently reported to have superior efficacy compared to diverse wound dressings against Pseudomonas aeruginosa biofilms in an ex vivo model. In the current study, the strong performance of CI vs. P. aeruginosa biofilm was confirmed using colony and colony drip-flow in vitro wound biofilm models. Similar in vitro efficacy of CI was also demonstrated against mature Staphylococcus aureus biofilms using the same models. Additionally, the rapid kill of mature S. aureus and P. aeruginosa colony biofilms was visualized by confocal microscopy using Live/Dead fluorescent stains. Superior in vitro efficacy of CI vs. staphylococcal biofilms was further demonstrated against methicillin-resistant S. aureus (MRSA) using multiple biofilm models with log reduction, Live/Dead, and metabolic endpoints. Comparator antimicrobial dressings, including silver-based dressings used throughout and other active agents used in individual models, elucidated only limited effects against the mature biofilms. Given the promising in vitro activity, CI was tested in an established mouse model of MRSA wound biofilm. CI had significantly greater impact on MRSA biofilm in mouse wounds than silver dressings or mupirocin based on Gram-stained histology sections and quantitative microbiology from biopsy samples (>4 log reduction in CFU/g vs. 0.7-1.6, p < 0.0001). The superior efficacy for CI in these in vitro and in vivo models suggests CI topical products may represent a better choice to address established bacterial biofilm in chronic wounds.

摘要

临床样本检查表明,大多数慢性伤口中存在细菌生物膜,大量证据表明生物膜对伤口愈合延迟有显著影响。生物膜中的细菌对抗菌剂具有高度耐受性,几乎没有数据可指导抗生物膜伤口治疗的选择。最近有报道称,在体外模型中,与多种伤口敷料相比,卡地姆碘(CI)对铜绿假单胞菌生物膜具有更高的疗效。在本研究中,使用菌落和菌落滴流体外伤口生物膜模型证实了CI对铜绿假单胞菌生物膜的强大性能。使用相同模型还证明了CI对成熟金黄色葡萄球菌生物膜具有相似的体外疗效。此外,使用活/死荧光染料通过共聚焦显微镜观察到成熟金黄色葡萄球菌和铜绿假单胞菌菌落生物膜的快速杀灭。使用具有对数减少、活/死和代谢终点的多种生物膜模型,进一步证明了CI对耐甲氧西林金黄色葡萄球菌(MRSA)的体外疗效优于葡萄球菌生物膜。对照抗菌敷料,包括全程使用的银基敷料和个别模型中使用的其他活性剂,对成熟生物膜的作用有限。鉴于其在体外的良好活性,在已建立的MRSA伤口生物膜小鼠模型中对CI进行了测试。根据革兰氏染色组织学切片和活检样本的定量微生物学分析,CI对小鼠伤口中的MRSA生物膜的影响明显大于银敷料或莫匹罗星(CFU/g减少>4个对数单位,而银敷料或莫匹罗星为0.7-1.6个对数单位,p < 0.0001)。CI在这些体外和体内模型中的卓越疗效表明,CI局部产品可能是治疗慢性伤口中已形成的细菌生物膜的更好选择。

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