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

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.