Antifungal activity of ibuprofen alone and in combination with fluconazoleagainst Candida species

Ibuprofen, a non-steroidal anti-inflammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg/ml, ib uprofen showed a rapid cidal activity against exponential growth phase C, a lbicans, accompanied by rapid and extensive leakage of intracellular K+, pe rmeation to propidium iodide, lysis of spheroplasts and severe membrane ult rastructural alterations. These results indicate that the killing of Candid a cells is due to direct damage to the cytoplasmic membrane. At 5 mg/ml, ib uprofen inhibited growth; however, it did not kill the yeasts and did not d irectly affect the cytoplasmic membrane. Evaluation of yeast metabolic vita lity with the fluorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. Th e combination of ibuprofen with fluconazole resulted in synergic activity w ith eight of the 12 Candida strains studied, including four of the five flu conazole-resistant strains. The MICs of fluconazole for the fluconazole-res istant strains decreased 2-128-fold when the drug was associated with ibupr ofen, When in combination with fluconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the p racticability of using ibuprofen, alone or in combination with azoles, in t he treatment of candidosis, particularly when applied topically, taking adv antage of the drug's antifungal and antiinflammatory properties.