Comparative in vitro antifungal activity of amphotericin B lipid complex, amphotericin B and fluconazole |
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Authors: | Carrillo-Muñoz A J Quindós G Tur C Ruesga M Alonso R del Valle O Rodriguez V Arévalo M P Salgado J Martin-Mazuelos E Bornay-Llinares F J del Palacio A Cuétara M Gasser I Hernández-Molina J M Pemán J |
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Affiliation: | Departamento de Microbiología, ACIA, Barcelona, Spain. acjm.acia@bcn.servicom.es |
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Abstract: | Amphotericin B (AMB) is considered the gold standard in the treatment of serious systemic mycoses in spite of its nephrotoxicity and adverse effects. Association with lipids enables larger doses of AMB to be given with a longer t((1/2)) and C(max), without the toxic effects at lower concentrations. Liposome-encapsulated AMB shows a lower affinity for mammalian cells and improves V(d), thus decreasing toxicity. Amphotericin B lipid complex (ABLC) is an AMB formulation associated with a biodegradable phospholipid matrix (5% molar) from which the drug is released by cell phospholipases. ABLC is recommended for serious mycoses refractory to conventional antifungal therapy or when AMB is contraindicated. We compared the in vitro antifungal activity of ABLC, AMB and fluconazole (FLZ) against 328 strains of clinically significant opportunistic fungi using a microdilution method (NCCLS, M-27A). 64.9% of the yeasts were inhibited by MIC of ABLC = AMB resulting in a similar or slightly superior efficacy compared to AMB when tested against Candida albicans, C. glabrata, C. guilliermondii, C. parapsilosis and C. tropicalis. Effectiveness against C. krusei was lower for ABLC (5.99 microg/ml for ABLC, 1.58 microg/ml for AMB). However, for Aspergillus fumigatus, the activities of AMB and ABLC were 1.62 and 2.46 microg/ml, respectively; A. niger 0.72 microg/ml, 0.76 microg/ml (ABLC and AMB, respectively); A. clavatus, A. candidus, A. tenuissima, A. corymbifera and Exophiala jeanselmei, Scedosporium spp. and Miceliophtora spp. showed a low susceptibility to both AMB formulations. ABLC is a useful alternative to AMB or FLZ for the treatment of severe fungal infections, due to the broad spectrum of antifungal actions observed in this study. |
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