Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms.
Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms.
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DOI：
10.1371/journal.pone.0234832
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Williams DL
中科院分区：
文献类型：
--
作者：
Miller M;Rogers JC;Badham MA;Cadenas L;Brightwell E;Adams J;Tyler C;Sebahar PR;Haussener TJ;Reddy HRK;Looper RE;Williams DL
生物膜受损的组织是糖尿病足溃疡等慢性伤口的一个重要因素。大多数（如果不是全部）临床使用的抗生素都针对浮游表型进行了优化。在这项研究中，进行了体外评估，以确定一流的抗生物膜抗生素系列的潜在功效，并将结果与当前的临床护理标准进行比较。该试剂 CZ-01179 被配制成水凝胶，并使用两种不同的方法针对耐甲氧西林金黄色葡萄球菌和铜绿假单胞菌 ATCC 27853 临床分离株的成熟生物膜进行测试。在第一种方法中，生物膜生长在琼脂表面的纤维素盘上。将外用制剂铺在纱布上并放置在生物膜上 24 小时。使用共焦和扫描电子显微镜对生物膜进行量化和成像。在第二种方法中，生物膜在改良的 CDC 生物膜反应器中的生物可吸收胶原试片上生长。将优惠券浸入处理中24小时。第一种方法评估疗效的能力有限。针对胶原蛋白上生长的生物膜的功效更加明确，与临床标准相比，CZ-01179 凝胶可以更大程度地消除已建立的生物膜。总之，CZ-01179 可能是一种有前途的针对生物膜表型的外用制剂。目前正在进行临床前工作以确定 CZ-01179 凝胶的可翻译潜力。
Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel.
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影响因子：
3.1
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