In vitro susceptibility and sterol biosynthesis of Candida albicans strains after long-term treatment with azoles in HIV-infected patients.
Over a period of 6 to 24 months a long term follow up of the in vitro antifungal susceptibility of 306 Candida 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).
Hundt
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Dermatologische Klinik und Poliklinik, Technischen Universität, München, Germany.
Hofmann
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D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000382:microbiology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D002180:Candidiasis, Oral / Q000188:drug therapy / Q000382:microbiology*; D002855:Chromatography, Thin Layer; D004352:Drug Resistance, Microbial; D005069:Evaluation Studies as Topic; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology / Q000627:therapeutic use*; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use*; D008826:Microbial Sensitivity Tests; D013261:Sterols / Q000096:biosynthesis*
D013261:Sterols; D017964:Itraconazole; D015725:Fluconazole; D007654:Ketoconazole