In vitro activity of 2-cyclohexylidenhydrazo-4-phenyl-thiazole compared with those of amphotericin B and fluconazole against clinical isolates of Candida spp. and fluconazole-resistant Candida albicans

Autor: De Logu, Alessandro, Saddi, Manuela, Cardia, Maria Cristina, Borgna, Rita, Sanna, Clara, Saddi, Barbara, Maccioni, Elias
Zdroj: Journal of Antimicrobial Chemotherapy (JAC); May 2005, Vol. 55 Issue: 5 p692-692, 1p
Abstrakt: <it>Objectives</it>: The aim of this study was to investigate the <it>in vitro</it> antifungal activity of an isothiosemicarbazone cyclic analogue against isolates of <it>Candida</it> spp. including fluconazole-resistant <it>Candida albicans</it>. <it>Methods</it>: We investigated the activity of 2-cyclohexylidenhydrazo-4-phenyl-thiazole (EM-01D2) against 114 clinical isolates of <it>Candida</it> spp., representing five different species, by microdilution, according to the NCCLS method 27-A. The activity against <it>C. albicans</it> biofilms was also investigated. Toxicity <it>in vitro</it> was evaluated by MTT reduction assay. <it>Results</it>: EM-01D2 demonstrated low toxicity, broad spectrum, fungicidal activity and was active against <it>C. albicans</it> and <it>Candida krusei</it> at concentrations lower than those shown by amphotericin B and fluconazole (<it>P</it> < 0.05). It maintained potent <it>in vitro</it> activity against fluconazole-resistant <it>C. albicans</it> isolates. Fungicidal activity occurred at concentrations 1–2 doubling dilutions greater than the corresponding MICs, and time–kill analysis indicated that a 99.9% loss of <it>C. albicans</it> viability occurred after 6 h of incubation in the presence of EM-01D2 at concentrations equal to four times the MIC. EM-01D2 was also active in inhibiting the growth of <it>C. albicans</it> ATCC 10231 biofilms, even though such inhibition occurred at concentrations higher than the MICs determined under planktonic growth conditions. However, when <it>C. albicans</it> biofilms were pre-exposed to subinhibitory concentrations of EM-01D2, a reduction of MIC<inf>50</inf> of amphotericin B was observed. <it>Conclusions</it>: Based on these results, EM-01D2 could represent a template for the development of novel fungicidal agents.
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