Drug repurposing against Candida auris: A systematic review.

Candida auris is a drug-resistant pathogen with several reported outbreaks. The treatment of C. auris infections is difficult due to a limited number of available antifungal drugs. Thus, finding alternative drugs through repurposing approaches would be clinically beneficial. A systematic search in PubMed, Scopus and Web of Science databases, as well as Google Scholar up to 1 November 2021, was conducted to find all articles with data regarding the antifungal activity of non-antifungal drugs against the planktonic and biofilm forms of C. auris. During database and hand searching, 290 articles were found, of which 13 were eligible for inclusion in the present study. Planktonic and biofilm forms have been studied in 11 and 8 articles (with both forms examined in 6 articles), respectively. In total, 22 and 12 drugs/compounds have been reported as repositionable against planktonic and biofilm forms of C. auris, respectively. Antiparasitic drugs, with the dominance of miltefosine, were the most common repurposed drugs against both forms of C. auris, followed by anticancer drugs (e.g. alexidine dihydrochloride) against the planktonic form and anti-inflammatory drugs (e.g. ebselen) against the biofilm form of the fungus. A collection of other drugs from various classes have also shown promising activity against C. auris. Following drug repurposing approaches, a number of drugs/compounds from various classes have been found to inhibit the planktonic and biofilm forms of C. auris. Accordingly, drug repurposing is an encouraging approach for discovering potential alternatives to conventional antifungal agents to combat drug resistance in fungi, especially C. auris.

New weapons to fight a new enemy: A systematic review of drug combinations against the drug-resistant fungus Candida auris.

Candida auris is an emerging and drug-resistant pathogen. Drug combination is a promising approach against such pathogens. This study was conducted to provide an overview of all the studied drug combinations against C. auris. Relevant articles reporting results of any drug/non-drug combinations against C. auris were found by a systematic search in PubMed, Scopus and Web of Science (ISI), and in Google Scholar up to 1 October 2020. From 187 articles retrieved in the primary search, 23 met the inclusion criteria. In total, 124 different combinations including antifungal with antifungal (45), antifungal with other antimicrobials (11), antifungal with non-antimicrobials (32), antifungal with natural compounds (25) and between natural compounds (11) have been reported. Complete or partial synergistic effects have been reported for 3 out of 45 (6.67%) combinations of two antifungal agents, 8 out of 11 (72.73%) combinations involving antifungal agents and antimicrobials, 15 out of 32 (46.88%) of combinations between antifungal agents with non-antimicrobials, 16 out of 25 (64%) of combinations involving antifungal agents and natural compounds, and 3 out of 11 (22.27%) of combinations involving multiple natural compounds. Antagonistic interactions have been reported for 1 out of 32 (3.13%) and 8 out of 25 (32%) of combinations between antifungal drugs with non-antimicrobials and with natural compounds, respectively. Different drugs/compounds could potentiate the activity of antifungal drugs using this approach. However, despite the availability of this promising initial data, many more studies will be required to elucidate whether favourable interactions observed in vitro might translate into tangible clinical benefits.