Abstract
The susceptibility of Candida albicans to a new antifungal triazole, voriconazole (UK-109,496), was investigated in 105 isolates obtained from the oral cavities of patients with human immunodeficiency virus (HIV) infection to study this drug's activity against fluconazole-susceptible and -resistant isolates. MICs were determined by a broth microdilution technique according to document M27-T from the National Committee for Clinical Laboratory Standards and by using a broth microdilution technique and a synthetic high-resolution medium. These antifungal susceptibility testing methods showed high levels of agreement (93% for fluconazole and 86% for voriconazole). Data from in vitro studies showed that voriconazole has good activity against fluconazole-susceptible and -resistant C. albicans isolates; the MICs at which 90% of all isolates were inhibited were 0.19 to 0.39 microgram/ml. We found that for isolates for which fluconazole MICs were high, voriconazole MICs were proportionally higher than those for fluconazole-susceptible C.albicans (P < 0.001). Pretreatment isolates from six patients with fluconazole-refractory esophageal candidiasis were included in the study. For these isolates the MICs were < or = 0.39 microgram/ml, and all patients responded to voriconazole. These results suggest that voriconazole is effective even in the treatment of fluconazole-refractory esophageal candidiasis and should be studied further to determine its clinical relevance in patients with HIV infection.
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- Barchiesi F., Colombo A. L., McGough D. A., Fothergill A. W., Rinaldi M. G. In vitro activity of a new antifungal triazole, D0870, against Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1994 Nov;38(11):2553–2556. doi: 10.1128/aac.38.11.2553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barchiesi F., Colombo A. L., McGough D. A., Fothergill A. W., Rinaldi M. G. In vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1994 Jul;38(7):1530–1533. doi: 10.1128/aac.38.7.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barry A. L., Brown S. D. In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species. Antimicrob Agents Chemother. 1996 Aug;40(8):1948–1949. doi: 10.1128/aac.40.8.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cameron M. L., Schell W. A., Bruch S., Bartlett J. A., Waskin H. A., Perfect J. R. Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1. Antimicrob Agents Chemother. 1993 Nov;37(11):2449–2453. doi: 10.1128/aac.37.11.2449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cartledge J. D., Midgley J., Youle M., Gazzard B. G. Itraconazole cyclodextrin solution--effective treatment for HIV-related candidosis unresponsive to other azole therapy. J Antimicrob Chemother. 1994 May;33(5):1071–1073. doi: 10.1093/jac/33.5.1071. [DOI] [PubMed] [Google Scholar]
- Johnson E. M., Warnock D. W., Luker J., Porter S. R., Scully C. Emergence of azole drug resistance in Candida species from HIV-infected patients receiving prolonged fluconazole therapy for oral candidosis. J Antimicrob Chemother. 1995 Jan;35(1):103–114. doi: 10.1093/jac/35.1.103. [DOI] [PubMed] [Google Scholar]
- Pfaller M. A., Dupont B., Kobayashi G. S., Müller J., Rinaldi M. G., Espinel-Ingroff A., Shadomy S., Troke P. F., Walsh T. J., Warnock D. W. Standardized susceptibility testing of fluconazole: an international collaborative study. Antimicrob Agents Chemother. 1992 Sep;36(9):1805–1809. doi: 10.1128/aac.36.9.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Redding S., Smith J., Farinacci G., Rinaldi M., Fothergill A., Rhine-Chalberg J., Pfaller M. Resistance of Candida albicans to fluconazole during treatment of oropharyngeal candidiasis in a patient with AIDS: documentation by in vitro susceptibility testing and DNA subtype analysis. Clin Infect Dis. 1994 Feb;18(2):240–242. doi: 10.1093/clinids/18.2.240. [DOI] [PubMed] [Google Scholar]
- Rex J. H., Pfaller M. A., Barry A. L., Nelson P. W., Webb C. D. Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia. NIAID Mycoses Study Group and the Candidemia Study Group. Antimicrob Agents Chemother. 1995 Jan;39(1):40–44. doi: 10.1128/aac.39.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruhnke M., Eigler A., Tennagen I., Geiseler B., Engelmann E., Trautmann M. Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection. J Clin Microbiol. 1994 Sep;32(9):2092–2098. doi: 10.1128/jcm.32.9.2092-2098.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vanden Bossche H., Marichal P., Odds F. C. Molecular mechanisms of drug resistance in fungi. Trends Microbiol. 1994 Oct;2(10):393–400. doi: 10.1016/0966-842x(94)90618-1. [DOI] [PubMed] [Google Scholar]