Skip to main content

Advertisement

SpringerLink
Log in

In vitro susceptibility and sterol biosynthesis ofCandida albicans strains after long term treatment with azoles in HIV-infected patients

In-vitro-Empfindlichkeit und Sterolbiosynthese vonCandida albicans-Isolaten nach Langzeittherapie mit Azolen bei HIV-infizierten Patienten

  • Special Addendum
  • Recent Trends In Antimycotic Chemotherapy
  • Published:
Infection Aims and scope Submit manuscript

Summary

Over a period of 6 to 24 months a long term follow up of thein vitro antifungal susceptibility of 306Candida albicans strains from 49 HIV-infected patients was performed. Using a microdilution test, the strains were tested against the azoles ketoconazole, itraconazole and fluconazole. The susceptibility range for fluconazole was between 1 and 128 mg/l, for itraconazole between 0.015 and 32 mg/l and for ketoconazole between 0.007 and 16 mg/l. 11.7% of the strains showed elevated IC30-values against ketoconazole, 9.1% against itraconazole and 10.1% against fluconazole. Sterol biosynthesis was examined by thin layer chromatography in 18 less sensitive strains and nine sensitive strains in the presence of ketoconazole. The proportion of ergosterol in the presence of ketoconazole at a concentration of 0.003 mg/l varied between 7.6% and 21.1% in sensitive strains and between 11.1% and 86.6% in less sensitive strains. In resistant control strains the proportion of ergosterol was 73% and 94.2%, respectively. Without ketoconazole the ergosterol proportion was >85% in all strains. There was a significant correlation between the IC30-values and the inhibition of ergosterol biosynthesis (p=0.05).

Zusammenfassung

Über einen Zeitraum von 6–24 Monaten wurde dieIn-vitro-Empfindlichkeit von 306Candida albicans-Isolaten von 49 HIV-infizierten Patienten untersucht. Die Empfindlichkeitsprüfungen erfolgten mittels Mikrodilutionstest unter Verwendung von Ketoconazol, Itraconazol und Fluconazol. Die IC30-Werte für Fluconazol lagen zwischen 1 mg/l und 128 mg/l, für Itraconazol zwischen 0,015 mg/l und 32 mg/l und für Ketoconazol zwischen 0,007 mg/l und 16 mg/l. 11,7% der Isolate zeigten eine verringerte Empfindlichkeit gegenüber Ketoconazol, 9,1% der Isolate gegen Itraconazol und 10,1% der Isolate gegen Fluconazol. Bei 18 Isolaten mit verminderter Empfindlichkeit und 9 empfindlichen Isolaten wurde die Sterolbiosynthese nach Zusatz von Ketoconazol dünnschichtchromatographisch untersucht. Der Ergosterolanteil lag in Gegenwart von 0,003 mg/l Ketoconazol zwischen 7,6% und 21,1% bei empfindlichen Isolaten und zwischen 11,1% und 86,6% bei weniger empfindlichen Isolaten. Resistente Kontrollstämme zeigten einen Ergosterolanteil von 73% bzw. 94,2%. Ohne Ketoconazolzusatz lag der Ergosterolanteil bei den Isolaten über 85%. Insgesamt zeigten die Untersuchungen eine gute Korrelation zwischen den IC30-Werten (Mikrodilutionstest) und der Inhibition der Ergosterolbiosynthese (p=0,05).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Horsburgh, C. R., Kirkpatrick, C. H., Teutsch, C. B. Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole: experience with twenty-one patients. Am. J. Med. 74 (1983) 23–29.

    Google Scholar 

  2. Holt, R. J., Azini, A. Miconazole resistantCandida. Lancet i (1978) 50–51.

    Google Scholar 

  3. Warnock, D. W., Warnock, E. M., Richardson, M. D., Vickers, C. F. H. Modified response to ketoconazole ofCandida albicans from a treatment failure. Lancet i (1983) 642–643.

    Google Scholar 

  4. Fox, R., Neal, K. R. Fluconazole resistantCandida in AIDS. Infection 22 (1991) 201–204.

    Google Scholar 

  5. Kitchen, V. S., Savage, M., Harris, J. R. W. Candida albicans resistance in AIDS. Infection 22 (1991) 204–205.

    Google Scholar 

  6. Parente, F., Cernuschi, M., Rizzardini, G. Opportunistic infections of the esophagus not responding to oral systemic antifungals in patients with AIDS: their frequency and treatment. Am. J. Gastroenterol. 86 (1991) 1729–1734.

    Google Scholar 

  7. Patty, F-H., Capano, D., Smith, S., Mangia, A. Development of resistance inCandida isolates from patients receiving prolonged antifungal therapy. Antimicrob. Agents Chemother. 34 (1991) 2302–2305.

    Google Scholar 

  8. Warnock, D. W., Burke, J. Fluconazole resistance inCandida glabrata. Lancet ii (1988) 1310.

    Google Scholar 

  9. Odds, F. C. Laboratory evaluation of antifungal agents: a comparative study of five imidazole derivates of clinical importance. J. Antimicrob. Chemother. 6 (1980) 749–761.

    Google Scholar 

  10. Ryley, J. F., Wilson, R. G., Barrett-Bee, K. J. Azole resistance inCandida albicans. Sabouraudia 22 (1993) 53–63.

    Google Scholar 

  11. Galgiani, J. N., Stevensen, D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob. Agents Chemother. 10 (1976) 721–726.

    Google Scholar 

  12. Hundt, W.: Verhalten derin vitro Antimykotikaempfindlichkeit und der Sterolbiosynthese vonCandida albicans unter einer Langzeittherapie mit Polyenen und Azolen bei HIV-infizierten Patienten mit Candida-Stomatitis und -Oesophagitis. Dissertation 1992. Universität des Saarlandes.

  13. Johnson, E. M., Richardson, M. D., Warnock, D. W. In-vitro resistance to imidazole antifungals inCandida albicans. Antimicrob. Chemother. 13 (1984) 547–558.

    Google Scholar 

  14. Hofmann, H., Hundt, W., Pees, H. Oral candidiasis in HIV-infected patients —in vitro-susceptibility ofCandida strains after long term antimycotic treatment. Z. Klin. Med. 45 (1990) 329–331.

    Google Scholar 

  15. Galgiani, J. N. Minireview: antifungal susceptibility tests. Antimicrob. Agents Chemother. 31 (1987) 1867–1870.

    Google Scholar 

  16. Korting, H. C., Georgii, A. Antimykotikatestung dermatovenerologisch bedeutsamer Hefen. Methoden, Ergebnisse und klinische Relevanz. Hautarzt 39 (1988) 343–347.

    Google Scholar 

  17. Radetsky, M., Wheeler, R. C., Roe, M. H., Todd, J. K. Microtiter broth dilution method for yeast susceptibility testing with validation by clinical outcome. J. Clin. Microb. 24 (1986) 600–606.

    Google Scholar 

  18. Graybill, J. R., Palou, E., Ahrens, J. Treatment of murine histoplasmosis with UK 49,858 (fluconazole). Am. Rev. Respir. Dis. 134 (1986) 768–770.

    Google Scholar 

  19. Rogers, T. E., Galgiani, J. N. Acitivity of fluconazole (UK 49,858) and ketoconazole againstCandida albicans in vitro andin vivo. Antimicrob. Agents Chemother. 30 (1986) 418–422.

    Google Scholar 

  20. Pye, G. W., Marriott, M. S. Inhibition of sterol C14 demethylation by imidazole-containing antifungals. Sabouraudia 20 (1982) 325–329.

    Google Scholar 

  21. Marriott, M. S. Inhibition of sterol biosynthesis inCandida albicans by imidazole-containing antifungals. J. Gen. Microbiol. 117 (1980) 253–255.

    Google Scholar 

  22. Van den Bossche, H., Willemsens, G., Colls, W., Lauwers, W. F. J., Jeune, L. Inhibition of ergosterol biosynthesis inCandida albicans by miconazole. In:W. Siegenthaler, R. Lüthy (eds.), Current chemotherapy. Proceedings of the 10th International Congress of Chemotherapy. American Society for Microbiology, Washington, D. C. 1978, pp. 228–231.

    Google Scholar 

  23. Van den Bossche, H., Lauwers, W., Willemsens, G., Marichal, P., Cornelissen, F., Cools, W. Molecular basis for the antimycotic and antibacterial activity of N-substituted imidazoles and triazoles: inhibition of isoprenoid biosynthesis. Pestic. Sci. 15 (1984) 188–198.

    Google Scholar 

  24. Van den Bossche, H., Willemsens, G., Cools, W., Cornelissen, F., Lauwers, W. F., Van Cutsem, J. In vitro andin vivo effects of the antimycotic drug ketoconazole on sterol synthesis. Antimicrob. Agents Chemother. 17 (1980) 922–928.

    Google Scholar 

  25. Yeagle, P. L., Martin, R. B., Lala, A. K., Lin, H. K., Block, K. Differential effect of cholesterol and lanosterol on artificial membranes. Proc. Natl. Acad. Sci. USA 74 (1977) 4924–4926.

    Google Scholar 

  26. Demel, R., Bruckdorfer, K. R., Van Deenen, L. L. M. Structural requirements of sterols for the interaction with lecithin at the air-water interface. Biochim. Biophys. Acta 255 (1972) 311–320.

    Google Scholar 

  27. Hitchcock, C. A., Brown, S. B., Evans, E. G. V., Adams, D. J. Cytochrome P-450-dependent 14a demethylation of lanosterol inCandida albicans. Biochem. J. 260 (1989) 549–556.

    Google Scholar 

  28. Willemsens, G., Cools, W., Van den Bossche, H. Effects of miconazole and ketoconazole on sterol synthesis in a subcellular fraction of yeast and mammalian cells. In:H. van den Bossche (ed.), The host invader interplay. Elsevier/North-Holland Biomedical Press, Amsterdam 1980, pp. 691–694.

    Google Scholar 

  29. Polak, A.: Mode of action studies. In:J. F. Ryley (ed.), Chemotherapy of fungal diseases. Springer Verlag 1990, pp. 153–182.

Download references

Author information

Authors and Affiliations

  1. Dermatologische Klinik und Poliklinik der Technischen Universität, Biedersteinerstraße 29, D-80805, München, Germany

    W. Hundt &  Heidelore Hofmann

Authors
  1. W. Hundt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heidelore Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hundt, W., Hofmann, H. In vitro susceptibility and sterol biosynthesis ofCandida albicans strains after long term treatment with azoles in HIV-infected patients. Infection 22, 124–131 (1994). https://doi.org/10.1007/BF01739023

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01739023

Keywords

Search

Navigation