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Their extensive use has led to the emergence of drug resistance, complicating antifungal therapy for yeast infections in critically ill patients. Combination therapy has become popular in clinical practice as a potential strategy to fight resistant fungal isolates. Recently, amphiphilic tobramycin analogues, <jats:bold>C<\/jats:bold><jats:sub><jats:bold>12<\/jats:bold><\/jats:sub> and <jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub>, were shown to display antifungal activities. Herein, the antifungal synergy of <jats:bold>C<\/jats:bold><jats:sub><jats:bold>12<\/jats:bold><\/jats:sub> and <jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub> with four azoles, fluconazole (FLC), itraconazole (ITC), posaconazole (POS) and voriconazole (VOR), was examined against seven <jats:italic>Candida albicans<\/jats:italic> strains. All tested strains were synergistically inhibited by <jats:bold>C<\/jats:bold><jats:sub><jats:bold>12<\/jats:bold><\/jats:sub> when combined with azoles, with the exception of <jats:italic>C. albicans<\/jats:italic> 64124 and MYA-2876 by FLC and VOR. Likewise, when combined with POS and ITC, <jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub> exhibited synergistic growth inhibition of all <jats:italic>C. albicans<\/jats:italic> strains, except <jats:italic>C. albicans<\/jats:italic> MYA-2876 by ITC. The combinations of FLC-<jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub> and VOR-<jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub> showed synergistic antifungal effect against three <jats:italic>C. albicans<\/jats:italic> and four <jats:italic>C. albicans<\/jats:italic> strains, respectively. Finally, synergism between <jats:bold>C<\/jats:bold><jats:sub><jats:bold>12<\/jats:bold><\/jats:sub>\/<jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub> and POS were confirmed by time-kill and disk diffusion assays. These results suggest the possibility of combining <jats:bold>C<\/jats:bold><jats:sub><jats:bold>12<\/jats:bold><\/jats:sub> or <jats:bold>C<\/jats:bold><jats:sub><jats:bold>14<\/jats:bold><\/jats:sub> with azoles to treat invasive fungal infections at lower administration doses or with a higher efficiency.<\/jats:p>","DOI":"10.1038\/srep17070","type":"journal-article","created":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T11:05:20Z","timestamp":1448276720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["A combination approach to treating fungal infections"],"prefix":"10.1038","volume":"5","author":[{"given":"Sanjib K.","family":"Shrestha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Y.","family":"Fosso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Garneau-Tsodikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,23]]},"reference":[{"key":"BFsrep17070_CR1","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1086\/599039","volume":"48","author":"DL Horn","year":"2009","unstructured":"Horn, D. 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