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

Background And Purpose: Emergence and development of antifungal drug resistance in species constitute a serious concern. as an emerging multidrug-resistant fungus is the most important public health threat with high levels of mortality and morbidity. Almost all 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 combination of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazole-resistant in comparison to other fluconazole-resistant species, including , , and 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 . However, the combination of fluconazole with ibuprofen resulted in a synergistic effect for 5 strains, including (n=2), (n=1), (n=1), and (n=1), by decreasing the MIC of fluconazole by 2-3 log dilutions.

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