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大蒜素与选定抗生素协同组合的杀菌效力动力学。

Kinetics of bactericidal potency with synergistic combination of allicin and selected antibiotics.

机构信息

Department of Chemical Engineering, Jadavpur University, Kolkata 700032, India.

Department of Chemical Engineering, Heritage Institute of Technology, Kolkata 700107, India.

出版信息

J Biosci Bioeng. 2022 Jun;133(6):567-578. doi: 10.1016/j.jbiosc.2022.02.007. Epub 2022 Mar 24.

Abstract

Synergistic therapy against the resurgence of bacterial pathogenesis is a modern trend for antibacterial chemotherapy. The phytochemical allicin, found in garlic extract is a commendable antimicrobial agent that can be used in synergistic combination with modern antibiotics. Determination of optimal antibacterial combination for the target species is vital for maximizing efficacy, lowering toxicity, total eradication of the bacterial cells and minimization of the risk of resistance generation. In this present investigation, Hill function-based pharmacodynamics models were employed to elaborate various time-kill kinetics parameters. The bactericidal potency of the synergistic combinations of allicin and individual antibiotic was assessed in comparison to their monotherapy application viz. using sole allicin and sole antibiotics (levofloxacin, ciprofloxacin, oxytetracycline, rifaximin, ornidazole and azithromycin) on actively growing Bacillus subtilis and Escherichia coli bacteria. Here, all the synergistic combinations showed significantly better (t-test p-value < 0.05) killing effect and biofilm reduction potential compared to their respective monotherapy application, where the highest killing effect was observed with rifaximin-allicin combination (kill rate was more than 5.5 h). Moreover, the average inhibition potential to protein denaturation by the synergistic combination group was significantly higher (3.4 fold) than the sole antibiotic's group manifests reduction in the dose-related toxicity. The potential of synergism between antibiotics and allicin combination demonstrated greater killing efficiency at significantly lower concentration compared to monotherapy with increased kill rates in all cases.

摘要

协同治疗细菌发病机制的反弹是抗菌化疗的现代趋势。大蒜提取物中的植物化学物质大蒜素是一种值得称赞的抗菌剂,可与现代抗生素联合使用。确定目标物种的最佳抗菌组合对于最大限度地提高疗效、降低毒性、彻底消灭细菌细胞和最小化产生耐药性的风险至关重要。在本研究中,基于 Hill 函数的药效动力学模型被用于阐述各种时间杀伤动力学参数。协同组合的杀菌效力大蒜素和单独抗生素与他们的单药应用相比进行了评估,即单独使用大蒜素和单独抗生素(左氧氟沙星、环丙沙星、土霉素、利福昔明、奥硝唑和阿奇霉素)对生长中的枯草芽孢杆菌和大肠杆菌进行评估。在这里,所有协同组合与各自的单药应用相比,显示出明显更好的(t 检验 p 值<0.05)杀菌效果和生物膜减少潜力,其中利福昔明-大蒜素组合的杀菌效果最高(杀菌率超过 5.5 小时)。此外,协同组合组对蛋白质变性的平均抑制潜力明显高于单独抗生素组(提高了 3.4 倍),表明降低了剂量相关的毒性。抗生素和大蒜素组合之间的协同作用潜力显示出在显著更低的浓度下具有更高的杀菌效率,在所有情况下都提高了杀菌率。

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