含金属离子和天然产物的新型夫西地酸乳膏抗多重耐药菌研究

Novel Fusidic Acid Cream Containing Metal Ions and Natural Products against Multidrug-Resistant Bacteria.

作者信息

Naseef Hani, Sahoury Yousef, Farraj Mohammad, Qurt Moammal, Abukhalil Abdallah D, Jaradat Nidal, Sabri Israr, Rabba Abdullah K, Sbeih Mahmmoud

机构信息

Pharmacy Department, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine.

Master Program in Clinical Laboratory Science, Faculty of Pharmacy, Nursing and Health Professions, Birzeit University, Ramallah P.O. Box 14, Palestine.

出版信息

Pharmaceutics. 2022 Aug 5;14(8):1638. doi: 10.3390/pharmaceutics14081638.

DOI:10.3390/pharmaceutics14081638

PMID:36015264

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9414967/

Abstract

BACKGROUND

Drug design and development to overcome antimicrobial resistance continues to be an area of research due to the evolution of microbial resistance mechanisms and the necessity for new treatments. Natural products have been used since the dawn of medicine to heal skin infections. The antimicrobial properties of fusidic acid, zinc sulfate, and copper sulfate have been studied and are well known. Furthermore, these compounds have different mechanisms of action in targeting microorganisms, either by inhibiting protein synthesis or bacterial cell walls. Therefore, their combination is expected to have synergistic activity in killing bacteria. However, the synergistic antimicrobial activity has not been evaluated in a cream formulation. Therefore, the objectives of this in vitro study were to develop and evaluate the synergistic efficacy of fusidic acid in combinations with natural products, including oleuropein, thyme oil, zinc sulfate, and copper sulfate, as a cream to eradicate fusidic-acid-resistant microorganisms in skin infections.

METHODS

Three different cream formulations were developed, compared, and labeled F1, F2, and F3. The compounds were studied for their antibacterial activity. In addition, the stability of the cream was investigated at 25 °C and 40 °C in plastic jars over three months.

RESULTS

The F2 formula has adequate physicochemical properties. Furthermore, it displays stable and better results than the marketed trade product and has potential inhibition zones (ZOI). Interestingly, considerable numbers (9.5%) of fusidic-acid-resistant Staphylococcus aureus (FRSA) isolates possessed a high resistance pattern with MIC ≥ 128 μg/mL. In contrast, most tested FRSA isolates (90.5%) had a low resistance pattern with MIC ≤ 8 μg/mL.

CONCLUSION

In conclusion, the F2 cream made with fusidic acid, oleuropein, thyme oil, zinc sulfate, and copper sulfate in the right amounts has stable physical and chemical properties and has potential against FRSA as an antimicrobial agent.

摘要

背景

由于微生物耐药机制的演变以及新治疗方法的必要性，克服抗菌药物耐药性的药物设计与开发仍是一个研究领域。自医学诞生以来，天然产物就被用于治疗皮肤感染。夫西地酸、硫酸锌和硫酸铜的抗菌特性已得到研究且广为人知。此外，这些化合物通过抑制蛋白质合成或细菌细胞壁来靶向微生物的作用机制各不相同。因此，它们的组合有望在杀灭细菌方面具有协同活性。然而，尚未在乳膏制剂中评估其协同抗菌活性。因此，本体外研究的目的是开发并评估夫西地酸与包括橄榄苦苷、百里香油、硫酸锌和硫酸铜在内的天然产物组合作为乳膏根除皮肤感染中耐夫西地酸微生物的协同疗效。

方法

开发、比较了三种不同的乳膏制剂，并分别标记为F1、F2和F3。研究了这些化合物的抗菌活性。此外，在塑料罐中于25℃和40℃下对乳膏的稳定性进行了为期三个月的研究。

结果

F2配方具有适当的理化性质。此外，它比市售商品表现出更稳定且更好的结果，并有潜在的抑菌圈（ZOI）。有趣的是，相当数量（9.5%）的耐夫西地酸金黄色葡萄球菌（FRSA）分离株具有高耐药模式，MIC≥128μg/mL。相比之下，大多数测试的FRSA分离株（90.5%）具有低耐药模式，MIC≤8μg/mL。