Abstract
Infections with fluconazole-resistant Candida albicans isolate have rarely been described in clinical settings other than oropharyngeal candidiasis in patients with late-stage AIDS. We report on two patients with leukemia who developed fungemia caused by fluconazole-resistant C. albicans after receiving fluconazole prophylaxis (400 mg/day) and empiric amphotericin B therapy (0.5 mg/kg of body weight per day). The fluconazole MICs for the isolates were > or = 64 micrograms/ml, and the isolates were resistant to other azoles and had membrane sterol changes consistent with a mutation in the delta 5,6-sterol desaturase gene. The lack of ergosterol in the cytoplasmic membrane of the fluconazole-resistant strains also imparted resistance to amphotericin B. Both patients were successfully treated with high-dose amphotericin B (1 to 1.25 mg/kg/day) and flucytosine (150 mg/kg/day).
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- Goodman J. L., Winston D. J., Greenfield R. A., Chandrasekar P. H., Fox B., Kaizer H., Shadduck R. K., Shea T. C., Stiff P., Friedman D. J. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992 Mar 26;326(13):845–851. doi: 10.1056/NEJM199203263261301. [DOI] [PubMed] [Google Scholar]
- Hitchcock C. A., Barrett-Bee K. J., Russell N. J. The lipid composition of azole-sensitive and azole-resistant strains of Candida albicans. J Gen Microbiol. 1986 Sep;132(9):2421–2431. doi: 10.1099/00221287-132-9-2421. [DOI] [PubMed] [Google Scholar]
- Howell S. A., Mallet A. I., Noble W. C. A comparison of the sterol content of multiple isolates of the Candida albicans Darlington strain with other clinically azole-sensitive and -resistant strains. J Appl Bacteriol. 1990 Nov;69(5):692–696. doi: 10.1111/j.1365-2672.1990.tb01564.x. [DOI] [PubMed] [Google Scholar]
- Lott T. J., Kuykendall R. J., Welbel S. F., Pramanik A., Lasker B. A. Genomic heterogeneity in the yeast Candida parapsilosis. Curr Genet. 1993 May-Jun;23(5-6):463–467. doi: 10.1007/BF00312635. [DOI] [PubMed] [Google Scholar]
- Marriott M. S. Inhibition of sterol biosynthesis in Candida albicans by imidazole-containing antifungals. J Gen Microbiol. 1980 Mar;117(1):253–255. doi: 10.1099/00221287-117-1-253. [DOI] [PubMed] [Google Scholar]
- Parkinson T., Falconer D. J., Hitchcock C. A. Fluconazole resistance due to energy-dependent drug efflux in Candida glabrata. Antimicrob Agents Chemother. 1995 Aug;39(8):1696–1699. doi: 10.1128/aac.39.8.1696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Price M. F., LaRocco M. T., Gentry L. O. Fluconazole susceptibilities of Candida species and distribution of species recovered from blood cultures over a 5-year period. Antimicrob Agents Chemother. 1994 Jun;38(6):1422–1424. doi: 10.1128/aac.38.6.1422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rex J. H., Cooper C. R., Jr, Merz W. G., Galgiani J. N., Anaissie E. J. Detection of amphotericin B-resistant Candida isolates in a broth-based system. Antimicrob Agents Chemother. 1995 Apr;39(4):906–909. doi: 10.1128/aac.39.4.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rex J. H., Rinaldi M. G., Pfaller M. A. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother. 1995 Jan;39(1):1–8. doi: 10.1128/aac.39.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanglard D., Kuchler K., Ischer F., Pagani J. L., Monod M., Bille J. Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob Agents Chemother. 1995 Nov;39(11):2378–2386. doi: 10.1128/aac.39.11.2378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vanden Bossche H., Marichal P., Gorrens J., Bellens D., Moereels H., Janssen P. A. Mutation in cytochrome P-450-dependent 14 alpha-demethylase results in decreased affinity for azole antifungals. Biochem Soc Trans. 1990 Feb;18(1):56–59. doi: 10.1042/bst0180056. [DOI] [PubMed] [Google Scholar]
- Wanger A., Mills K., Nelson P. W., Rex J. H. Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for antifungal susceptibility testing: enhanced ability to detect amphotericin B-resistant Candida isolates. Antimicrob Agents Chemother. 1995 Nov;39(11):2520–2522. doi: 10.1128/aac.39.11.2520. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wingard J. R., Merz W. G., Rinaldi M. G., Johnson T. R., Karp J. E., Saral R. Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med. 1991 Oct 31;325(18):1274–1277. doi: 10.1056/NEJM199110313251803. [DOI] [PubMed] [Google Scholar]
- Wingard J. R., Merz W. G., Rinaldi M. G., Miller C. B., Karp J. E., Saral R. Association of Torulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. Antimicrob Agents Chemother. 1993 Sep;37(9):1847–1849. doi: 10.1128/aac.37.9.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]