Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Sep;37(9):1962–1965. doi: 10.1128/aac.37.9.1962

Fluconazole resistance in Candida glabrata.

C A Hitchcock 1, G W Pye 1, P F Troke 1, E M Johnson 1, D W Warnock 1
PMCID: PMC188100  PMID: 8239613

Abstract

We report a case of infection with Candida glabrata in which the organism became resistant to fluconazole and in which pre- and posttreatment isolates were available for comparison. The organism was cross-resistant to ketoconazole and itraconazole, in common with other azole-resistant yeasts. Fluconazole was a potent inhibitor of cytochrome P-450-dependent 14 alpha-sterol demethylase (P-450DM) in lysates of cells from both susceptible and resistant cultures (50% inhibitory concentration, 0.2 microM), indicating that resistance was unrelated to changes in P-450DM. Instead, it appeared to arise from a permeability barrier to fluconazole, since resistant cells were unable to take up radiolabelled drug.

Full text

PDF
1964

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barrett-Bee K. J., Lane A. C., Turner R. W. The mode of antifungal action of tolnaftate. J Med Vet Mycol. 1986 Apr;24(2):155–160. doi: 10.1080/02681218680000221. [DOI] [PubMed] [Google Scholar]
  2. Connolly T. J., Carruthers A., Melchior D. L. Effect of bilayer cholesterol content on reconstituted human erythrocyte sugar transporter activity. J Biol Chem. 1985 Mar 10;260(5):2617–2620. [PubMed] [Google Scholar]
  3. Evans T. G., Mayer J., Cohen S., Classen D., Carroll K. Fluconazole failure in the treatment of invasive mycoses. J Infect Dis. 1991 Dec;164(6):1232–1235. doi: 10.1093/infdis/164.6.1232. [DOI] [PubMed] [Google Scholar]
  4. Fox R., Neal K. R., Leen C. L., Ellis M. E., Mandal B. K. Fluconazole resistant candida in AIDS. J Infect. 1991 Mar;22(2):201–204. doi: 10.1016/0163-4453(91)91767-r. [DOI] [PubMed] [Google Scholar]
  5. Fromtling R. A. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev. 1988 Apr;1(2):187–217. doi: 10.1128/cmr.1.2.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hitchcock C. A., Barrett-Bee K. J., Russell N. J. Inhibition of 14 alpha-sterol demethylase activity in Candida albicans Darlington does not correlate with resistance to azole. J Med Vet Mycol. 1987 Oct;25(5):329–333. [PubMed] [Google Scholar]
  7. Hitchcock C. A., Barrett-Bee K. J., Russell N. J. The lipid composition and permeability to the triazole antifungal antibiotic ICI 153066 of serum-grown mycelial cultures of Candida albicans. J Gen Microbiol. 1989 Jul;135(7):1949–1955. doi: 10.1099/00221287-135-7-1949. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Hitchcock C. A., Brown S. B., Evans E. G., Adams D. J. Cytochrome P-450-dependent 14 alpha-demethylation of lanosterol in Candida albicans. Biochem J. 1989 Jun 1;260(2):549–556. doi: 10.1042/bj2600549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hitchcock C. A. Cytochrome P-450-dependent 14 alpha-sterol demethylase of Candida albicans and its interaction with azole antifungals. Biochem Soc Trans. 1991 Aug;19(3):782–787. doi: 10.1042/bst0190782. [DOI] [PubMed] [Google Scholar]
  11. Hitchcock C. A., Dickinson K., Brown S. B., Evans E. G., Adams D. J. Interaction of azole antifungal antibiotics with cytochrome P-450-dependent 14 alpha-sterol demethylase purified from Candida albicans. Biochem J. 1990 Mar 1;266(2):475–480. doi: 10.1042/bj2660475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hitchcock C. A., Russell N. J., Barrett-Bee K. J. Sterols in Candida albicans mutants resistant to polyene or azole antifungals, and of a double mutant C. albicans 6.4. Crit Rev Microbiol. 1987;15(1):111–115. doi: 10.3109/10408418709104454. [DOI] [PubMed] [Google Scholar]
  13. Holt R. J., Azmi A. Miconazole-resistant Candida. Lancet. 1978 Jan 7;1(8054):50–51. doi: 10.1016/s0140-6736(78)90403-8. [DOI] [PubMed] [Google Scholar]
  14. Horsburgh C. R., Jr, Kirkpatrick C. H. Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole: experience with twenty-one patients. Am J Med. 1983 Jan 24;74(1B):23–29. doi: 10.1016/0002-9343(83)90511-9. [DOI] [PubMed] [Google Scholar]
  15. Kitchen V. S., Savage M., Harris J. R. Candida albicans resistance in AIDS. J Infect. 1991 Mar;22(2):204–205. doi: 10.1016/0163-4453(91)91789-z. [DOI] [PubMed] [Google Scholar]
  16. Pfaller M. A., Rinaldi M. G., Galgiani J. N., Bartlett M. S., Body B. A., Espinel-Ingroff A., Fromtling R. A., Hall G. S., Hughes C. E., Odds F. C. Collaborative investigation of variables in susceptibility testing of yeasts. Antimicrob Agents Chemother. 1990 Sep;34(9):1648–1654. doi: 10.1128/aac.34.9.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ryley J. F., Wilson R. G., Barrett-Bee K. J. Azole resistance in Candida albicans. Sabouraudia. 1984;22(1):53–63. [PubMed] [Google Scholar]
  18. Smith D., Boag F., Midgley J., Gazzard B. Fluconazole resistant candida in AIDS. J Infect. 1991 Nov;23(3):345–346. doi: 10.1016/0163-4453(91)93584-y. [DOI] [PubMed] [Google Scholar]
  19. Smith K. J., Warnock D. W., Kennedy C. T., Johnson E. M., Hopwood V., Van Cutsem J., Vanden Bossche H. Azole resistance in Candida albicans. J Med Vet Mycol. 1986 Apr;24(2):133–144. [PubMed] [Google Scholar]
  20. Smith R. A., Hitchcock C. A., Evans E. G., Lacey C. J., Adams D. J. The identification of Candida albicans strains by restriction fragment length polymorphism analysis of DNA. J Med Vet Mycol. 1989;27(6):431–434. [PubMed] [Google Scholar]
  21. Warnock D. W., Burke J., Cope N. J., Johnson E. M., von Fraunhofer N. A., Williams E. W. Fluconazole resistance in Candida glabrata. Lancet. 1988 Dec 3;2(8623):1310–1310. doi: 10.1016/s0140-6736(88)92919-4. [DOI] [PubMed] [Google Scholar]
  22. Warnock D. W., Johnson E. M., Richardson M. D., Vickers C. F. Modified response to ketoconazole of Candida albicans from a treatment failure. Lancet. 1983 Mar 19;1(8325):642–643. doi: 10.1016/s0140-6736(83)91809-3. [DOI] [PubMed] [Google Scholar]
  23. Willocks L., Leen C. L., Brettle R. P., Urquhart D., Russell T. B., Milne L. J. Fluconazole resistance in AIDS patients. J Antimicrob Chemother. 1991 Dec;28(6):937–939. doi: 10.1093/jac/28.6.937. [DOI] [PubMed] [Google Scholar]
  24. Yeagle P. L., Martin R. B., Lala A. K., Lin H. K., Bloch K. Differential effects of cholesterol and lanosterol on artificial membranes. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4924–4926. doi: 10.1073/pnas.74.11.4924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. de Kruyff B., de Greef W. J., van Eyk R. V., Demel R. A., van Deenen L. L. The effect of different fatty acid and sterol composition on the erythritol flux through the cell membrane of Acholeplasma laidlawii. Biochim Biophys Acta. 1973 Mar 16;298(2):479–499. doi: 10.1016/0005-2736(73)90375-1. [DOI] [PubMed] [Google Scholar]
  26. vanden Bossche H., Marichal P., Odds F. C., Le Jeune L., Coene M. C. Characterization of an azole-resistant Candida glabrata isolate. Antimicrob Agents Chemother. 1992 Dec;36(12):2602–2610. doi: 10.1128/aac.36.12.2602. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES