Synergistic effect of ibuprofen with itraconazole and fluconazole against Cryptococcus neoformans

Abstract

The present study investigated the association of the non-steroidal anti-inflammatory drug ibuprofen with itraconazole, fluconazole and amphotericin B against Cryptococcus neoformans isolates. The minimal inhibitory concentration (MIC) was found according to M27-A3 protocol and in vitro interactions were evaluated using checkerboard microdilution method. Synergism was demonstrated between azoles and ibuprofen for most isolates. However, no synergistic effects were seen when amphotericin B was combined with ibuprofen. Therefore, our results suggest that ibuprofen presents clinical potential when combined with azole drugs in the treatment of cryptococcosis.

Itraconazole in the treatment of basal cell carcinoma: A case‐based review of the literature

“…While there is evidence to suggest a degree of synergism between ibuprofen and itraconazole when used to treat fungal infections, it has also been recognised that itraconazole's binding of SMO protein is independent of its ability to inhibit CYP450-dependent ergosterol synthesis in fungi cell membranes. 5,10 Although innumerable review articles discuss the anti-Hh properties of intraconazole in molecular and murine studies, this systematic review highlights that the evidence on the clinical efficacy of intraconazole in the treatment of BCC remains sparse. Its use in locally advanced and/or metastatic BCC, where its application is most likely to be relevant, is limited to case reports/series as monotherapy, with the addition of small phase 2 proof of concept studies for when used in combination with other Hh pathway inhibitors.…”

“…Unlike itraconazole, COX‐2 inhibitors have not been shown to exhibit anti‐Hh pathway properties. While there is evidence to suggest a degree of synergism between ibuprofen and itraconazole when used to treat fungal infections, it has also been recognised that itraconazole’s binding of SMO protein is independent of its ability to inhibit CYP450‐dependent ergosterol synthesis in fungi cell membranes 5,10 …”

Fluconazole-COX Inhibitor Hybrids: A Dual-Acting Class of Antifungal Azoles

“… 41 It was shown that ibuprofen can alter the expression of the genes encoding the efflux pumps and that it may also act directly as an efflux pump blocker. 42 , 43 …”

“…albicans. , A similar effect was observed for a combination of FLC and FK506, a 23-membered-ring macrolide immunosuppressant, that also acts as a broad-spectrum inhibitor of pleiotropic drug resistance ATP-binding cassette transporters. ,, FLC -resistant isolates revert to FLC susceptible after incubation with ibuprofen yet retain high levels of expression of CDR1 and CDR2 efflux pumps . It was shown that ibuprofen can alter the expression of the genes encoding the efflux pumps and that it may also act directly as an efflux pump blocker. , …”

“…41 It was shown that ibuprofen can alter the expression of the genes encoding the efflux pumps and that it may also act directly as an efflux pump blocker. 42,43 The arachidonic acid pathway has been associated with the yeast-to-hyphae morphogenesis in several species of Candida, 44,45 the most commonly diagnosed pathogens causing fungal-born infectious diseases in humans. 46,47 In mammals, nonsteroidal anti-inflammatory drugs such as COX inhibitors reduce the formation of prostaglandins generated via the arachidonic acid pathway.…”