Synergistic effect of ibuprofen with itraconazole and fluconazole against Cryptococcus neoformans

Letícia Fernandes Da Rocha,Adelina Mezzari,Bruna Pippi,Alexandre Meneghello Fuentefria

doi:10.1590/s2175-97902019000318599

Letícia Fernandes Da Rocha, Adelina Mezzari + Show 2 more

Open Access

https://doi.org/10.1590/s2175-97902019000318599

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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.

Highlights

Opportunistic pathogenic fungi such as Candida, Aspergillus and Cryptococcus species are responsible for systemic infections affecting mainly immunodeficient patients such as neonates, transplanted and patients with acquired immunodeficiency syndrome (AIDS) (Grimaldi et al, 2010)
The present study aims to test the association of ibuprofen with itraconazole, fluconazole and amphotericin B against C. neoformans isolates
The geometric mean of minimal inhibitory concentration (MIC) was lower for ITC (0.66 μg/mL) than for FLC (1.74 μg/mL) and amphotericin B (AMB) (6.17 μg/mL)

Summary

INTRODUCTION

Opportunistic pathogenic fungi such as Candida, Aspergillus and Cryptococcus species are responsible for systemic infections affecting mainly immunodeficient patients such as neonates, transplanted and patients with acquired immunodeficiency syndrome (AIDS) (Grimaldi et al, 2010). Cryptococcosis is an infection mainly caused by encapsulated yeast fungus such as Cryptococcus neoformans. This microorganism is found in bird droppings and contaminated soil with higher prevalence in tropical and subtropical regions (Ramose-Silva et al, 2012). Combination therapy with two or more antifungals has the potential to reduce antifungal resistance and decrease toxicity of each drug, but its side effects should be evaluated with caution (Hatipoglu, Hatipoglu, 2013). Ibuprofen is accessible because it is inexpensive and has shown synergistic effect when combined with fluconazole in Candida strains (Hatipoglu, Hatipoglu, 2013; Liu et al, 2014). The present study aims to test the association of ibuprofen with itraconazole, fluconazole and amphotericin B against C. neoformans isolates

MATERIAL AND METHODS

RESULTS AND DISCUSSION

CONCLUSION

CONFLICT OF INTEREST