Bayramov Danir, Li Zhenghao, Patel Esha, Izadjoo Mina, Kim Hosan, Neff Jennifer
Allvivo Vascular, Inc., 20914 Bake Parkway, Suite 100, Lake Forest, CA 92630.
Trideum Biosciences, 4539 Metropolitan Court, Frederick, MD 21704.
Mil Med. 2018 Mar 1;183(suppl_1):481-486. doi: 10.1093/milmed/usx135.
Wound infections are a common complication of combat-related injuries that significantly increase morbidity and mortality. Multi-drug resistant (MDR) organisms and their associated biofilms play a significant role in the pathogenicity and chronicity of wound infections. A critical barrier to progress in the treatment of traumatic wounds is the need for broad spectrum antimicrobials that are effective against biofilms and compatible with topical delivery. In this study, we present the in vitro efficacy of two de novo designed cationic, antimicrobial peptides and related topical formulations against single species and polymicrobial biofilms of MDR bacteria. Minimum biofilm eradication concentrations for peptides ranged from 0.7 μM for Staphylococcus aureus to 13.2 μM for Pseudomonas aeruginosa. Varying pH did not adversely impact peptide activity, however, in the presence of albumin, minimum biofilm eradication concentrations generally increased. When formulated into gels or dressings, both peptides eradicated mono- and polymicrobial biofilms of MDR pathogens. The biocompatibility index (BI) was found to be greater than one for both ASP-1 and ASP-2, with a slightly greater (more favorable) BI for ASP-2. The BIs for both peptides were greater than BIs previously reported for commonly used topical antimicrobial agents. The antimicrobial peptides and related formulations presented provide a promising platform for treatment of wound biofilms to improve outcomes for those injured in combat.
伤口感染是战斗相关损伤的常见并发症,会显著增加发病率和死亡率。多重耐药(MDR)微生物及其相关生物膜在伤口感染的致病性和慢性化过程中起着重要作用。创伤伤口治疗进展的一个关键障碍是需要对生物膜有效且与局部给药兼容的广谱抗菌药物。在本研究中,我们展示了两种新设计的阳离子抗菌肽及其相关局部制剂对MDR细菌单一菌种和多菌种生物膜的体外疗效。肽的最低生物膜根除浓度范围从金黄色葡萄球菌的0.7 μM到铜绿假单胞菌的13.2 μM。不同的pH值对肽活性没有不利影响,然而,在存在白蛋白的情况下,最低生物膜根除浓度通常会增加。当制成凝胶或敷料时,两种肽都能根除MDR病原体的单一菌种和多菌种生物膜。发现ASP - 1和ASP - 2的生物相容性指数(BI)均大于1,ASP - 2的BI略高(更有利)。两种肽的BI均大于先前报道的常用局部抗菌剂的BI。所呈现的抗菌肽及其相关制剂为治疗伤口生物膜提供了一个有前景的平台,以改善战斗中受伤人员的治疗效果。