Hoffmann Joseph P, Friedman Jessica K, Wang Yihui, McLachlan James B, Sammarco Mimi C, Morici Lisa A, Roy Chad J
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, United States.
Department of Surgery, Tulane University School of Medicine, New Orleans, LA, United States.
Front Microbiol. 2020 Jan 23;10:3106. doi: 10.3389/fmicb.2019.03106. eCollection 2019.
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 by determining the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), against different strains of methicillin-resistant (MRSA), resulting estimates of which approximated the positive control (bacitracin). To evaluate 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 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 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.
皮肤和软组织感染中抗生素耐药性的患病率增加是当前医学面临的一个令人担忧的公共卫生挑战。已开发出一种组合式广谱杀菌防腐剂（“ASP”），作为一种局部应用的解决方案，用于应对在此背景下可能遇到的潜在耐药和多微生物感染伤口。通过测定对不同耐甲氧西林（MRSA）菌株的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）来评估ASP - 105，其结果估计接近阳性对照（杆菌肽）。为了评估杀菌剂的疗效，我们利用小鼠全层伤口模型来研究细菌感染和伤口愈合动力学。小鼠背部经实验性创伤并感染生物发光的MRSA。感染的伤口进行固定、包扎，并用ASP - 105、赋形剂（阴性对照）或杆菌肽进行局部治疗。使用成像系统监测细菌负荷和伤口愈合情况，并通过对伤口敷料进行扫描电子显微镜检查来评估生物膜形成情况。用ASP - 105治疗在感染的前3天显著降低了细菌负荷，并抑制了手术敷料上MRSA生物膜的形成。值得注意的是，用ASP - 105治疗在几乎所有（80%；4/5）治疗组中对任何可检测到的MRSA都产生了杀菌效果。所有接受赋形剂对照的小鼠由于实验性感染而出现高度MRSA发光和化脓的伤口床。ASP - 105疗法在无MRSA感染的情况下促进了自然愈合。这项研究的结果表明，新型“ASP”组合式局部防腐剂可直接用于伤口，作为一种有效的广谱杀菌剂，对抗耐药菌，而不会损伤伤口床，也不会阻碍与伤口愈合相关的自然修复过程。有必要进一步研究该杀菌制剂在严重伤口感染情况下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场景中的实用性。
