Indifferent Effect of Nonsteroidal Antiinflammatory Drugs (Nsaids) Combined With Fluconazole Against Multidrugresistant Candida Auris

Background and purpose: emergence and development of antifungal drug resistance in candida species constitute a serious concern. candida auris as an emerging multidrugresistant 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 antiinflammatory drugs (nsaids), such as ibuprofen, diclofenac and aspirin with fluconazole against fluconazoleresistant c. auris in comparison to other fluconazoleresistant candida species, including c. albicans, c. glabrata, c. parapsilosis, c. tropicalis, and c. krusei originating from patients with candidiasis. results: the mic ranges of fluconazoleibuprofen and fluconazolediclofenac decreased from 32256 to 32128 and 16256 μg/ml, respectively and remained the same for fluconazoleaspirin 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 23 log2 dilutions. conclusion: although the interaction of nsaids with fluconazole was not synergistic against fluconazoleresistant c. auris isolates, no antagonism was observed for any combinations. therefore, combination with newer azole agents needs to be conducted.