Interactions of Posaconazole and Flucytosine against Cryptococcus neoformans
Open Access
- 1 May 2001
- journal article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 45 (5), 1355-1359
- https://doi.org/10.1128/aac.45.5.1355-1359.2001
Abstract
A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of Cryptococcus neoformans . Synergy, defined as a fractional inhibitory concentration (FIC) index of 4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of C. neoformans 486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination. While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against C. neoformans in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections.Keywords
This publication has 23 references indexed in Scilit:
- Itraconazole and flucytosine+itraconazole combination in the treatment of experimental cryptococcosis in hamstersMycoses, 1995
- Use of amphotericin B with azole antifungal drugs: what are we doing?Antimicrobial Agents and Chemotherapy, 1995
- Antagonistic interactions between azoles and amphotericin B with yeasts depend on azole lipophilia for special test conditions in vitroAntimicrobial Agents and Chemotherapy, 1995
- Cross-resistance to polyene and azole drugs in Cryptococcus neoformansAntimicrobial Agents and Chemotherapy, 1995
- Fluconazole Combined with Flucytosine for Treatment of Cryptococcal Meningitis in Patients with AIDSClinical Infectious Diseases, 1994
- Therapy of experimental meningeal and disseminated cryptococcosisMycoses, 1993
- Combination Therapy in Experimental Invasive AspergillosisThe Journal of Infectious Diseases, 1993
- Treatment of murine cryptococcal meningitis with an SCH 39304-amphotericin B combinationAntimicrobial Agents and Chemotherapy, 1991
- Combination Therapy of Experimental Candidiasis, Cryptococcosis, Aspergillosis and Wangiellosis in MiceChemotherapy, 1987
- A Comparison of Amphotericin B Alone and Combined with Flucytosine in the Treatment of Cryptoccal MeningitisNew England Journal of Medicine, 1979