Masadeh Majed M, Alzoubi Karem H, Masadeh Majd M, Aburashed Zainah O
Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Clin Pharmacol. 2021 May 11;13:83-90. doi: 10.2147/CPAA.S297903. eCollection 2021.
The continuous increase in the incidence of bacterial resistance to existing antibiotics represents a worldwide health burden. A surrogate strategy to combat such crisis is to find compounds that restore the antimicrobial activity of the already existing antibiotics against multidrug resistant bacteria. Metformin is a commonly used antidiabetic medication. It has proven benefits in other diseases including cancer, aging-related and infectious diseases. In this study, the potential effect of metformin as an adjuvant therapy to antibiotics was investigated.
Two multidrug resistant bacterial strains were used; methicillin-resistant (MRSA; ATCC 33,591) and multidrug resistant (ATCC BAA-2114). To assess its efficacy, metformin was combined with several antibiotics: levofloxacin, chloramphenicol, rifampicin, ampicillin, and doxycycline. The antibacterial effect of metformin was tested using the micro broth dilution method. The minimum inhibitory concentration (MIC) was also measured. Cytotoxicity studies were also performed on mammalian cells to assess its safety.
Metformin exhibited an antibacterial effect when combined with the antibiotics on the two tested strains. It also showed low toxicity on the mammalian cells. Moreover, synergetic studies showed that metformin enhanced the effect of the combined antibiotics, as these combinations provide either a synergistic or additive effect with significant reduction in the MIC.
Metformin exerts an adjuvant antibacterial effect; thus, it could be a possible candidate as an adjuvant therapy to reduce antimicrobial resistance.
细菌对现有抗生素耐药性的发生率持续上升，这是一个全球性的健康负担。应对这一危机的替代策略是找到能够恢复现有抗生素对多重耐药菌抗菌活性的化合物。二甲双胍是一种常用的抗糖尿病药物。它在包括癌症、与衰老相关的疾病和传染病在内的其他疾病中已被证明具有益处。在本研究中，研究了二甲双胍作为抗生素辅助治疗的潜在效果。
使用了两种多重耐药菌株；耐甲氧西林金黄色葡萄球菌（MRSA；ATCC 33591）和多重耐药菌（ATCC BAA - 2114）。为了评估其疗效，将二甲双胍与几种抗生素联合使用：左氧氟沙星、氯霉素、利福平、氨苄西林和强力霉素。采用微量肉汤稀释法测试二甲双胍的抗菌效果。还测量了最低抑菌浓度（MIC）。对哺乳动物细胞进行了细胞毒性研究以评估其安全性。
二甲双胍与抗生素联合使用时，对两种测试菌株均表现出抗菌作用。它对哺乳动物细胞也显示出低毒性。此外，协同研究表明，二甲双胍增强了联合使用抗生素的效果，因为这些组合提供了协同或相加作用，MIC显著降低。
二甲双胍具有辅助抗菌作用；因此，它可能是一种作为辅助治疗以降低抗菌耐药性的潜在候选药物。
