CIISA-Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisboa, Portugal.
PLoS One. 2019 Jul 24;14(7):e0220000. doi: 10.1371/journal.pone.0220000. eCollection 2019.
Diabetic foot infections (DFIs) are a frequent complication of Diabetes mellitus and a major cause of nontraumatic limb amputations. The Gram-positive bacterium Staphylococcus aureus, known for its resilient biofilms and antibiotic resistant profile, is the most frequent DFI pathogen. It is urgent to develop innovative treatments for these infections, being the antimicrobial peptide (AMP) nisin a potential candidate. We have previously proposed the use of a guar gum biogel as a delivery system for nisin. Here, we evaluated the potential of the nisin-biogel to enhance the efficacy of conventional antibiotics and antiseptics against DFIs S. aureus clinical isolates.
A collection of 23 S. aureus strains isolated from DFI patients, including multidrug- and methicillin-resistant strains, was used. The antimicrobial activity of the nisin-biogel was tested alone and in different combinations with the antiseptic chlorhexidine and the antibiotics clindamycin, gentamicin and vancomycin. Isolates' in vitro susceptibility to the different protocols was assessed using broth microdilution methods in order to determine their ability to inhibit and/or eradicate established S. aureus biofilms. Antimicrobials were added to the 96-well plates every 8 h to simulate a typical DFI treatment protocol. Statistical analysis was conducted using RCBD ANOVA in SPSS.
The nisin-biogel showed a high antibacterial activity against biofilms formed by DFI S. aureus. The combined protocol using nisin-biogel and chlorhexidine presented the highest efficacy in biofilm formation inhibition, significantly higher (p<0.05) than the ones presented by the antibiotics-based protocols tested. Regarding biofilm eradication, there were no significant differences (p>0.05) between the activity of the combination nisin-biogel plus chlorhexidine and the conventional antibiotic-based protocols.
Results provide a valuable contribution for the development of complementary strategies to conventional antibiotics protocols. A combined protocol including chlorhexidine and nisin-biogel could be potentially applied in medical centres, contributing for the reduction of antibiotic administration, selection pressure on DFI pathogens and resistance strains dissemination.
糖尿病足感染（DFI）是糖尿病的常见并发症，也是非创伤性肢体截肢的主要原因。金黄色葡萄球菌是革兰氏阳性菌，以其弹性生物膜和抗生素耐药性而闻名，是最常见的 DFI 病原体。迫切需要开发针对这些感染的创新治疗方法，抗菌肽（AMP）乳链菌肽是一种潜在的候选药物。我们之前提出使用瓜尔胶生物凝胶作为乳链菌肽的递送系统。在这里，我们评估了乳链菌肽-生物凝胶在增强传统抗生素和防腐剂对 DFI 金黄色葡萄球菌临床分离株疗效方面的潜力。
使用了从 DFI 患者中分离的 23 株金黄色葡萄球菌菌株的集合，包括多药和耐甲氧西林菌株。单独测试了乳链菌肽-生物凝胶的抗菌活性，并与防腐剂洗必泰以及抗生素克林霉素、庆大霉素和万古霉素进行了不同的组合测试。使用肉汤微量稀释法评估了分离物对不同方案的体外敏感性，以确定它们抑制和/或消除已建立的金黄色葡萄球菌生物膜的能力。每隔 8 小时向 96 孔板中添加抗菌药物，以模拟典型的 DFI 治疗方案。使用 SPSS 中的 RCBD ANOVA 进行统计分析。
乳链菌肽-生物凝胶对 DFI 金黄色葡萄球菌形成的生物膜表现出很高的抗菌活性。使用乳链菌肽-生物凝胶和洗必泰的联合方案在生物膜形成抑制方面表现出最高的疗效，明显高于（p<0.05）测试的基于抗生素的方案。关于生物膜清除，乳链菌肽-生物凝胶加洗必泰的组合活性与基于常规抗生素的方案之间没有显著差异（p>0.05）。
研究结果为开发针对常规抗生素方案的补充策略提供了有价值的贡献。包括洗必泰和乳链菌肽-生物凝胶的联合方案可在医疗中心中潜在应用，有助于减少抗生素的使用、对 DFI 病原体和耐药菌株传播的选择压力。
