Antifungal activity of ibuprofen alone and in combination with fluconazole against Candida species

Abstract

Ibuprofen, a non-steroidal anti-in¯ammatory drug, exhibited antimicrobial activity against Candida albicans and non-albicans strains. At 10 mg=ml, ibuprofen showed a rapid cidal activity against exponential growth phase C. albicans, accompanied by rapid and extensive leakage of intracellular K , permeation to propidium iodide, lysis of spheroplasts and severe membrane ultrastructural alterations. These results indicate that the killing of Candida cells is due to direct damage to the cytoplasmic membrane. At 5 mg=ml, ibuprofen inhibited growth; however, it did not kill the yeasts and did not directly affect the cytoplasmic membrane. Evaluation of yeast metabolic vitality with thē uorescent probe FUN-1 showed that growth inhibition induced by the fungistatic drug concentration was due to metabolic alterations. The combination of ibuprofen with uconazole resulted in synergic activity with eight of the 12 Candida strains studied, including four of the ®ve¯uconazole-resistant strains. The MICs of¯uconazole for thē uconazole-resistant strains decreased 2±128-fold when the drug was associated with ibuprofen. When in combination with¯uconazole, MICs for ibuprofen decreased by up to 64-fold for all the 12 strains studied. These results point to the practicability of using ibuprofen, alone or in combination with azoles, in the treatment of candidosis, particularly when applied topically, taking advantage of the drug's antifungal and antiin¯ammatory properties.

Effect of Some Non steroidal Anti-Inflammatory Drugs on Growth, Adherence and Mature Biofilms of <i>Candida spp</i><i>.</i>

“…especially C. krusei that agree with several studies [38,44]. The mechanism proposed for fungicidal activity of ibuprofen is in conformity with its lipophilic character [45].…”

Characterization of women with a history of recurrent vulvovaginal candidosis

“…fluconazole. There is an efflux of the drug in fluconazole-resistant Candida strains (26). However, in our study population fluconazole had only been used by a few of our patients.…”

In vitro Synergistic Effects of Anthracycline Antitumor Agents and Fluconazole Against Azole-Resistant Candida albicans Clinical Isolates

“…This structural difference may also influence the uptake of these compounds into fungal cells. However, the synergistic effects of aclarubicin and daunorubicin with fluconazole were similar, i.e., the FICIs of aclarubicin and daunorubicin were 0.0083-0.0162 and [4][5][6][7], HMG-CoA reductase inhibitors (statins) [8,9], and non-steroidal antiinflammatory drugs [10,11]. In addition to their synergistic effect with fluconazole, anthracyclines have a unique function.…”

“…Consequently, research on compounds that have synergistic effects with azole agents has flourished. Calcineurin inhibitors [4][5][6][7], HMGCoA reductase inhibitors (statins) [8,9], and non-steroidal antiinflammatory drugs (NSAIDs) are representative examples [10,11]. Low-molecular-weight antitumor agents are divided into six classes based on their mechanism of action: antimetabolites, alkylating agents, topoisomerase inhibitors, microtubule inhibitors, microtubule depolymerizing agents, and molecular target agents.…”