BACKGROUND: A computerized machine, SPECTRAmax 340, was used to evaluate the recently reported phenomenon of antagonism of the polyene amphotericin B (AMB) in Candida albicans pre-exposed to the triazole fluconazole (FLZ). METHODS: We investigated growth inhibition by varying concentrations of AMB in seven isolates of C. albicans pre-exposed to FLZ (50 microg/ml) for 18 h. All isolates were obtained on sequential visits from human immunodeficiency virus-infected patients not treated with FLZ. RESULTS: Antagonism of AMB activity was observed in 5, 4, 2 and a single isolate for 0.5, 1, 2 and 3 microg/ml of the antifungal, respectively. In the majority of Candida isolates, antagonism was seen within a concentration range of 0.5-1.0 microg/ml AMB; 1 Candida strain (HK1-Sa) was resistant to 3 microg/ml AMB. Higher concentrations of AMB (>3 microg/ml) killed both the controls and FLZ-pre-exposed Candida cells. No significant differences were observed between the periods of antagonism observed for any of the sequential isolates or for any of the AMB concentrations or in the maxima of the growth curves obtained for all Candida isolates. CONCLUSION: We conclude that the SPECTRAmax system is a useful tool to evaluate in vitro pharmacodynamic interactions between antifungal regimens within a fluid culture system, and provides information that cannot be obtained using traditional plate assay systems.
BACKGROUND: A computerized machine, SPECTRAmax 340, was used to evaluate the recently reported phenomenon of antagonism of the polyene amphotericin B (AMB) in Candida albicans pre-exposed to the triazole fluconazole (FLZ). METHODS: We investigated growth inhibition by varying concentrations of AMB in seven isolates of C. albicans pre-exposed to FLZ (50 microg/ml) for 18 h. All isolates were obtained on sequential visits from human immunodeficiency virus-infectedpatients not treated with FLZ. RESULTS: Antagonism of AMB activity was observed in 5, 4, 2 and a single isolate for 0.5, 1, 2 and 3 microg/ml of the antifungal, respectively. In the majority of Candida isolates, antagonism was seen within a concentration range of 0.5-1.0 microg/ml AMB; 1 Candida strain (HK1-Sa) was resistant to 3 microg/ml AMB. Higher concentrations of AMB (>3 microg/ml) killed both the controls and FLZ-pre-exposed Candida cells. No significant differences were observed between the periods of antagonism observed for any of the sequential isolates or for any of the AMB concentrations or in the maxima of the growth curves obtained for all Candida isolates. CONCLUSION: We conclude that the SPECTRAmax system is a useful tool to evaluate in vitro pharmacodynamic interactions between antifungal regimens within a fluid culture system, and provides information that cannot be obtained using traditional plate assay systems.
Authors: Melissa D Johnson; Conan MacDougall; Luis Ostrosky-Zeichner; John R Perfect; John H Rex Journal: Antimicrob Agents Chemother Date: 2004-03 Impact factor: 5.191