Indifferent effect of nonsteroidal anti-inflammatory drugs (NSAIDs) combined with fluconazole against multidrug-resistant Candida auris

Fatemeh   Ahangarkani; Sadegh Khodavaisy; Shahram   Mahmoudi; Tahereh   Shokohi; Mohammad Sadegh  Rezai; Hamed  Fakhim; Eric   Dannaoui; Saharnaz  Faraji; Anuradha  Chowdhary; Jacques   F.Meis; Hamid   Badali

doi:10.18502/cmm.5.3.1743

Fatemeh Ahangarkani
Sadegh Khodavaisy
Shahram Mahmoudi
Tahereh Shokohi
Mohammad Sadegh Rezai
Hamed Fakhim
Eric Dannaoui
Saharnaz Faraji
Anuradha Chowdhary
Jacques F.Meis
Hamid Badali

DOI: https://doi.org/10.18502/cmm.5.3.1743

Keywords: Antifungal drugs, Candida auris, Multidrug-resistant, NSAIDs

Abstract

Background and Purpose: Emergence and development of antifungal drug resistance in Candida species constitute a serious concern. Candida auris as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all C. auris isolates are resistant to fluconazole, and there have been reports of elevated minimum inhibitory concentrations (MICs) to amphotericin B and echinocandins. To overcome the growing challenge of antifungal resistance, a valuable alternative option would be the use of drug combination.

Materials and Methods: The present study evaluated the in vitro combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant C. auris in comparison to other fluconazole-resistant Candida species, including C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei originating from patients with candidiasis.

Results: The MIC ranges of fluconazole-ibuprofen and fluconazole-diclofenac decreased from 32-256 to 32-128 and 16-256 µg/ml, respectively and remained the same for fluconazole-aspirin against C. auris. However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including C. albicans (n=2), C. tropicalis (n=1), C. glabrata (n=1), and C. krusei (n=1), by decreasing the MIC of fluconazole by 2-3 log₂ dilutions.

Conclusion: Although the interaction of NSAIDs with fluconazole was not synergistic against fluconazole-resistant C. auris isolates, no antagonism was observed for any combinations. Therefore, combination with newer azole agents needs to be conducted.