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In situ Treatment With Novel Microbiocide Inhibits Methicillin Resistant Staphylococcus aureus in a Murine Wound Infection Model.
Frontiers in Microbiology ( IF 4.0 ) Pub Date : 2020-01-23 , DOI: 10.3389/fmicb.2019.03106
Joseph P Hoffmann 1 , Jessica K Friedman 2 , Yihui Wang 1 , James B McLachlan 1 , Mimi C Sammarco 2 , Lisa A Morici 1 , Chad J Roy 1, 3
Affiliation  

Increased prevalence of antibiotic resistance in skin and soft tissue infections is a concerning public health challenge currently facing medical science. A combinatory, broad spectrum biocidal antiseptic has been developed ("ASP") as a topically applied solution to potential resistant and polymicrobial infected wounds that may be encountered in this context. The ASP-105 designate was evaluated in vitro by determining the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), against different strains of methicillin-resistant Staphylococcus aureus (MRSA), resulting estimates of which approximated the positive control (bacitracin). To evaluate in vivo microbicide efficacy, we utilized a murine full thickness wound model to study bacterial infection and wound healing kinetics. Mice were experimentally wounded dorsally and infected with bioluminescent MRSA. The infected wound was splinted, dressed and treated topically with either ASP-105, vehicle (-control), or bacitracin. Bacterial burden and wound healing was monitored using an in vivo imaging system and evaluation of biofilm formation using scanning electron microscopy of wound dressing. Treatment with ASP-105 significantly reduced bacterial burdens in the first 3 days of infection and inhibited MRSA biofilm formation on the surgical dressing. Notably, treatment with ASP-105 resulted in a sterilizing effect of any detectable MRSA in nearly all (80%; 4/5) of treatment group. All mice receiving vehicle control developed highly MRSA-luminescent and purulent wound beds as a result of experimental infection. The ASP-105 therapy facilitated natural healing in the absence of MRSA infection. Results of this study suggests that that the novel "ASP" combinatory topical antiseptic can be used directly in wounds as a potent, broad-spectrum microbicide against drug resistant S. aureus without injury to the wound bed and impediment of natural restorative processes associated with wound healing. Further studies are warranted to test the effectiveness of this biocidal formulation against other recalcitrant bacterial and fungal pathogens in the context of serious wound infections, and to assess utility of use in both clinical and self-treat scenarios.

中文翻译:

在小鼠伤口感染模型中,新型杀菌剂的原位治疗可抑制耐甲氧西林的金黄色葡萄球菌。

皮肤和软组织感染中抗生素抗药性的增加是当前医学界面临的有关公共卫生的挑战。已经开发了组合的广谱杀生物防腐剂(“ ASP”)作为在这种情况下可能遇到的潜在的耐药性和被微生物感染的伤口的局部应用的解决方案。通过确定针对不同菌株的耐甲氧西林金黄色葡萄球菌(MRSA)的最低抑菌浓度(MIC)和最低杀菌浓度(MBC),对ASP-105指定物进行了体外评估,得出的估计值近似于阳性对照(细菌素) 。为了评估体内杀微生物剂的功效,我们利用鼠类全厚度伤口模型研究细菌感染和伤口愈合动力学。实验性地将小鼠背部受伤,并用生物发光的MRSA感染。将感染的伤口夹板,包扎并用ASP-105,溶媒(对照)或杆菌肽进行局部治疗。使用体内成像系统监测细菌负担和伤口愈合,并使用伤口敷料的扫描电子显微镜评估生物膜形成。用ASP-105处理可显着减少感染前3天的细菌负担,并抑制手术敷料上的MRSA生物膜形成。值得注意的是,ASP-105的治疗在几乎所有治疗组(80%; 4/5)中均产生了任何可检测的MRSA的灭菌效果。作为实验感染的结果,接受媒介物对照的所有小鼠均产生高度MRSA发光和脓性伤口床。在没有MRSA感染的情况下,ASP-105疗法有助于自然愈合。这项研究的结果表明,新型“ ASP”组合型局部防腐剂可以直接作为抗药性金黄色葡萄球菌的有效,广谱杀菌剂用于伤口,而不会损害伤口床,也不会阻碍与伤口相关的自然修复过程康复。在进一步的严重伤口感染的情况下,有必要进行进一步的研究来测试这种杀菌剂对其他顽固细菌和真菌病原体的有效性,并评估其在临床和自我治疗中的实用性。抗药性金黄色葡萄球菌的广谱杀菌剂,不会损伤伤口床,也不会阻碍与伤口愈合相关的自然恢复过程。在进一步的严重伤口感染的情况下,有必要进行进一步的研究来测试这种杀菌剂对其他顽固细菌和真菌病原体的有效性,并评估其在临床和自我治疗中的实用性。抗药性金黄色葡萄球菌的广谱杀菌剂,不会损伤伤口床,也不会阻碍与伤口愈合相关的自然恢复过程。在进一步的严重伤口感染的情况下,有必要进行进一步的研究来测试这种杀菌剂对其他顽固性细菌和真菌病原体的有效性,并评估其在临床和自我治疗中的实用性。
更新日期:2020-01-23
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