Van de Vliet Lauren, Vackier Thijs, Thevissen Karin, Decoster David, Steenackers Hans P
MiCA Lab, Centre of Microbial and Plant Genetics (CMPG), Department Microbial and Molecular Systems, KU Leuven, 3001 Leuven, Belgium.
CMPG-PFI (Plant-Fungus Interactions Group of Centre of Microbial and Plant Genetics), Department Microbial and Molecular Systems, KU Leuven, 3001 Leuven, Belgium.
Antibiotics (Basel). 2024 Oct 10;13(10):949. doi: 10.3390/antibiotics13100949.
BACKGROUND/OBJECTIVES: The rise and spread of antimicrobial resistance complicates the treatment of bacterial wound pathogens, further increasing the need for newer, effective therapies. Azoles such as miconazole have shown promise as antibacterial compounds; however, they are currently only used as antifungals. Previous research has shown that combining azoles with quaternary ammonium compounds yields synergistic activity against fungal pathogens, but the effect on bacterial pathogens has not been studied yet.
In this study, the focus was on finding active synergistic combinations of imidazoles and quaternary ammonium compounds against (multidrug-resistant) bacterial pathogens through checkerboard assays. Experimental evolution in liquid culture was used to evaluate the possible emergence of resistance against the most active synergistic combination.
Several promising synergistic combinations were identified against an array of Gram-positive pathogens: miconazole/domiphen bromide, ketoconazole/domiphen bromide, clotrimazole/domiphen bromide, fluconazole/domiphen bromide and miconazole/benzalkonium chloride. Especially, miconazole with domiphen bromide exhibits potential, as it has activity at a low concentration against a broad range of pathogens and shows an absence of strong resistance development over 11 cycles of evolution.
This study provides valuable insight into the possible combinations of imidazoles and quaternary ammonium compounds that could be repurposed for (topical) wound treatment. Miconazole with domiphen bromide shows the highest application potential as a possible future wound therapy. However, further research is needed into the mode of action of these compounds and their efficacy and toxicity in vivo.
背景/目的：抗菌药物耐药性的出现和传播使细菌性伤口病原体的治疗变得复杂，进一步增加了对更新、有效疗法的需求。咪康唑等唑类已显示出作为抗菌化合物的潜力；然而，它们目前仅用作抗真菌剂。先前的研究表明，将唑类与季铵化合物联合使用可产生针对真菌病原体的协同活性，但对细菌病原体的影响尚未得到研究。
在本研究中，重点是通过棋盘法找到咪唑类和季铵化合物针对（多重耐药）细菌病原体的活性协同组合。使用液体培养中的实验进化来评估对最具活性的协同组合产生耐药性的可能性。
针对一系列革兰氏阳性病原体确定了几种有前景的协同组合：咪康唑/度米芬溴铵、酮康唑/度米芬溴铵、克霉唑/度米芬溴铵、氟康唑/度米芬溴铵和咪康唑/苯扎氯铵。特别是，咪康唑与度米芬溴铵表现出潜力，因为它在低浓度下对多种病原体具有活性，并且在11个进化周期中未显示出强烈的耐药性发展。
本研究为咪唑类和季铵化合物可能重新用于（局部）伤口治疗的组合提供了有价值的见解。咪康唑与度米芬溴铵作为未来可能的伤口治疗方法显示出最高的应用潜力。然而，需要进一步研究这些化合物的作用方式及其在体内的功效和毒性。
