Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. Candida invasive infections represent an increasing challengefor clinicians, with an assigned mortality rate of around 40% (1–3). The extensive use of fluconazole in both prophylaxis and therapy has resulted in the emergence of resistance (4–6). Knowledge of the mechanisms underlying resistance is of cru-cial importance, since it might support approaches to achieve re-version, leading to the development of new therapeutic strategies. Alterations in the Candida albicans transcriptome induced by az-ole exposure have been extensively reported (5, 7, 8). However, few studies have tackled antifungal resistance reversion. Previously, we showed that the antifungal resistance conferre