Synergism of the Antimicrobial Agents Miconazole, Bacitracin and Polymyxin B

The antibacterial activity of a combination of miconazole with bacitracin against Staphylococcus epidermidis or Staphylococcus aureus, was greater than the sum of the effects observed with the two drugs independently. Since no uptake changes were observed, this synergism may originate from a combined effect of miconazole and bacitracin on the biosynthesis of the carrier lipid, undecaprenyl-phosphate, resulting in an impairment of cell wall integrity. The synergism between these drugs and polymyxin B may be due to an increased accessibility of the cell membrane to polymyxin B. Miconazole and bacitracin, alone or in combination, are completely inactive against Escherichia coli. Since polymyxin B disturbs the permeability barrier and stimulates the uptake of miconazole, the synergism of polymyxin B, miconazole and bacitracin may originate from the ability of miconazole and bacitracin to penetrate the bacterial membranes in the presence of polymyxin B.