In vitro susceptibilities of yeasts to a new antifungal triazole, SCH 39304: Effects of test conditions and relation to in vivo efficacy

K. A. McIntyre, J. N. Galgiani

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23 Scopus citations


We used six candidal strains (two Candida albicans and one each of four other species) to study the effects of test conditions on the activity of SCH 39304 compared with that of fluconazole in broth macro- and microdilution assays. Increasing the inoculum from 102 to 105 yeasts per ml raised the MICs for all isolates up to > 512-fold. In contrast, results with a 50% turbidimetric endpoint (50% inhibitory concentration; IC( 1/2 )) varied no more than twofold. Similar effects were seen with fluconazole, and both drugs were found to have an associated delay in onset of action. Acidity was found to increase both MICs and IC( 1/2 )s. Other effects were observed among four synthetic media, but a consistent pattern was not identified. Incubation temperatures of 37, 35 and 30°C yielded equivalent results. Broth microdilution IC( 1/2 )s against most of 40 isolates of C. albicans were 0.31 μg/ml ± fourfold for SCH 39304 and 0.16 μg/ml ± twofold for fluconazole. Treatment of experimental candidiasis in rats with SCH 39304 and fluconazole resulted in 50% effective doses of 0.33 and 0.49 mg/kg per day, respectively. In contrast, another C. albicans isolate, previously identified as resistant to other azoles, had IC( 1/2 )s of 20 μg of SCH 39304 per ml and, in vivo, a 50% effective dose of 2.25 mg/kg per day. We conclude that the in vivo efficacy of SCH 39304 correlates with MIC results when broth macrodilution testing is performed with a small inoculum and with IC( 1/2 ) results which are independent of inoculum size.

Original languageEnglish (US)
Pages (from-to)1095-1100
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Issue number7
StatePublished - Jan 1 1989


ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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