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. 1997 Jan;41(1):180–183. doi: 10.1128/aac.41.1.180

In vitro studies of activities of the antifungal triazoles SCH56592 and itraconazole against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts.

J N Galgiani 1, M L Lewis 1
PMCID: PMC163681  PMID: 8980776

Abstract

We investigated the effects of various assay conditions on the activities of two antifungal drugs, SCH56592 and itraconazole, against seven species of fungi by the broth macrodilution testing procedure proposed by the National Committee for Clinical Laboratory Standards (NCCLS). For both drugs, which are insoluble in water, the concentration and type of solubilizing agent produced differences in drug activity. Starting inoculum size differences from 10(2) to 10(5) yeast cells per ml resulted in approximately a fourfold effect on the MIC of both drugs, but other significant differences were not observed with variations in synthetic medium composition, pH, buffering reagent, or incubation temperature. Under standardized conditions of reference method M27-T with 1% polyethylene glycol as the solubilizing agent, median MICs of SCH56592 and itraconazole of 60 and 125 mg/ml, respectively, were demonstrated for 110 strains (12 to 23 strains for each of seven species). Broth microdilution results were typically severalfold higher than broth macrodilution results. We conclude that the NCCLS standard reference method can be applied without modification to the testing of SCH56592 and itraconazole, but particular attention to solubilizing the agents is critical to obtaining consistent results.

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Selected References

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  1. Calhoun D. L., Galgiani J. N. Analysis of pH and buffer effects on flucytosine activity in broth dilution susceptibility testing of Candida albicans in two synthetic media. Antimicrob Agents Chemother. 1984 Sep;26(3):364–367. doi: 10.1128/aac.26.3.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clemons K. V., Homola M. E., Stevens D. A. Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo. Antimicrob Agents Chemother. 1995 May;39(5):1169–1172. doi: 10.1128/aac.39.5.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cook R. A., McIntyre K. A., Galgiani J. N. Effects of incubation temperature, inoculum size, and medium on agreement of macro- and microdilution broth susceptibility test results for yeasts. Antimicrob Agents Chemother. 1990 Aug;34(8):1542–1545. doi: 10.1128/aac.34.8.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Denning D. W., Lee J. Y., Hostetler J. S., Pappas P., Kauffman C. A., Dewsnup D. H., Galgiani J. N., Graybill J. R., Sugar A. M., Catanzaro A. NIAID Mycoses Study Group Multicenter Trial of Oral Itraconazole Therapy for Invasive Aspergillosis. Am J Med. 1994 Aug;97(2):135–144. doi: 10.1016/0002-9343(94)90023-x. [DOI] [PubMed] [Google Scholar]
  5. Dismukes W. E., Bradsher R. W., Jr, Cloud G. C., Kauffman C. A., Chapman S. W., George R. B., Stevens D. A., Girard W. M., Saag M. S., Bowles-Patton C. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med. 1992 Nov;93(5):489–497. doi: 10.1016/0002-9343(92)90575-v. [DOI] [PubMed] [Google Scholar]
  6. Espinel-Ingroff A., Rodríguez-Tudela J. L., Martínez-Suárez J. V. Comparison of two alternative microdilution procedures with the National Committee for Clinical Laboratory Standards reference macrodilution method M27-P for in vitro testing of fluconazole-resistant and -susceptible isolates of Candida albicans. J Clin Microbiol. 1995 Dec;33(12):3154–3158. doi: 10.1128/jcm.33.12.3154-3158.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Galgiani J. N., Stevens D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob Agents Chemother. 1976 Oct;10(4):721–728. doi: 10.1128/aac.10.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Galgiani J. N. Susceptibility testing of fungi: current status of the standardization process. Antimicrob Agents Chemother. 1993 Dec;37(12):2517–2521. doi: 10.1128/aac.37.12.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galgiant J. N., Stevens D. A. Turbidimetric studies of growth inhibition of yeasts with three drugs: inquiry into inoculum-dependent susceptibility testing, time of onset of drug effect, and implications for current and newer methods. Antimicrob Agents Chemother. 1978 Feb;13(2):249–254. doi: 10.1128/aac.13.2.249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graybill J. R., Stevens D. A., Galgiani J. N., Dismukes W. E., Cloud G. A. Itraconazole treatment of coccidioidomycosis. NAIAD Mycoses Study Group. Am J Med. 1990 Sep;89(3):282–290. doi: 10.1016/0002-9343(90)90339-f. [DOI] [PubMed] [Google Scholar]
  11. Karyotakis N. C., Dignani M. C., Anaissie E. J. SCH 51048, a new antifungal triazole active against hematogenous Candida krusei infections in neutropenic mice. Antimicrob Agents Chemother. 1995 Mar;39(3):775–777. doi: 10.1128/AAC.39.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McIntyre K. A., Galgiani J. N. In vitro susceptibilities of yeasts to a new antifungal triazole, SCH 39304: effects of test conditions and relation to in vivo efficacy. Antimicrob Agents Chemother. 1989 Jul;33(7):1095–1100. doi: 10.1128/aac.33.7.1095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McIntyre K. A., Galgiani J. N. pH and other effects on the antifungal activity of cilofungin (LY121019). Antimicrob Agents Chemother. 1989 May;33(5):731–735. doi: 10.1128/aac.33.5.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pfaller M. A., Bale M. J., Buschelman B., Rhomberg P. Antifungal activity of a new triazole, D0870, compared with four other antifungal agents tested against clinical isolates of Candida and Torulopsis glabrata. Diagn Microbiol Infect Dis. 1994 Jun;19(2):75–80. doi: 10.1016/0732-8893(94)90116-3. [DOI] [PubMed] [Google Scholar]
  15. Pfaller M. A., Barry A. L. In vitro susceptibilities of clinical yeast isolates to three antifungal agents determined by the microdilution method. Mycopathologia. 1995;130(1):3–9. doi: 10.1007/BF01104343. [DOI] [PubMed] [Google Scholar]
  16. Pfaller M. A., Burmeister L., Bartlett M. S., Rinaldi M. G. Multicenter evaluation of four methods of yeast inoculum preparation. J Clin Microbiol. 1988 Aug;26(8):1437–1441. doi: 10.1128/jcm.26.8.1437-1441.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pfaller M. A., Cabezudo I., Hollis R., Huston B., Wenzel R. P. The use of biotyping and DNA fingerprinting in typing Candida albicans from hospitalized patients. Diagn Microbiol Infect Dis. 1990 Nov-Dec;13(6):481–489. doi: 10.1016/0732-8893(90)90080-f. [DOI] [PubMed] [Google Scholar]
  18. Pfaller M. A., Grant C., Morthland V., Rhine-Chalberg J. Comparative evaluation of alternative methods for broth dilution susceptibility testing of fluconazole against Candida albicans. J Clin Microbiol. 1994 Feb;32(2):506–509. doi: 10.1128/jcm.32.2.506-509.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pfaller M. A., Messer S. A., Coffmann S. Comparison of visual and spectrophotometric methods of MIC endpoint determinations by using broth microdilution methods to test five antifungal agents, including the new triazole D0870. J Clin Microbiol. 1995 May;33(5):1094–1097. doi: 10.1128/jcm.33.5.1094-1097.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reagan D. R., Pfaller M. A., Hollis R. J., Wenzel R. P. Characterization of the sequence of colonization and nosocomial candidemia using DNA fingerprinting and a DNA probe. J Clin Microbiol. 1990 Dec;28(12):2733–2738. doi: 10.1128/jcm.28.12.2733-2738.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rex J. H., Bennett J. E., Sugar A. M., Pappas P. G., van der Horst C. M., Edwards J. E., Washburn R. G., Scheld W. M., Karchmer A. W., Dine A. P. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. Candidemia Study Group and the National Institute. N Engl J Med. 1994 Nov 17;331(20):1325–1330. doi: 10.1056/NEJM199411173312001. [DOI] [PubMed] [Google Scholar]
  22. Rogers T. E., Galgiani J. N. Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother. 1986 Sep;30(3):418–422. doi: 10.1128/aac.30.3.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sewell D. L., Pfaller M. A., Barry A. L. Comparison of broth macrodilution, broth microdilution, and E test antifungal susceptibility tests for fluconazole. J Clin Microbiol. 1994 Sep;32(9):2099–2102. doi: 10.1128/jcm.32.9.2099-2102.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stevens D. A. Itraconazole and fluconazole for treatment of coccidioidomycosis. Clin Infect Dis. 1994 Mar;18(3):470–470. doi: 10.1093/clinids/18.3.470. [DOI] [PubMed] [Google Scholar]
  25. Sugar A. M., Picard M. Treatment of murine pulmonary blastomycosis with SCH 51048, a broad-spectrum triazole antifungal agent. Antimicrob Agents Chemother. 1995 Apr;39(4):996–997. doi: 10.1128/aac.39.4.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Villareal K. M., Cook R. A., Galgiani J. N., Wenzel R. P., Pappas P. G., Pottage J. C., Jr, Gallis H. A., Crane L. R. Comparative analysis of three antifungal susceptibility test methods against prospectively collected Candida species. Diagn Microbiol Infect Dis. 1994 Feb;18(2):89–94. doi: 10.1016/0732-8893(94)90071-x. [DOI] [PubMed] [Google Scholar]
  27. Wheat J., Hafner R., Korzun A. H., Limjoco M. T., Spencer P., Larsen R. A., Hecht F. M., Powderly W. Itraconazole treatment of disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trial Group. Am J Med. 1995 Apr;98(4):336–342. doi: 10.1016/s0002-9343(99)80311-8. [DOI] [PubMed] [Google Scholar]
  28. Wheat J., Hafner R., Wulfsohn M., Spencer P., Squires K., Powderly W., Wong B., Rinaldi M., Saag M., Hamill R. Prevention of relapse of histoplasmosis with itraconazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1993 Apr 15;118(8):610–616. doi: 10.7326/0003-4819-118-8-199304150-00006. [DOI] [PubMed] [Google Scholar]
  29. Witt M. D., Lewis R. J., Larsen R. A., Milefchik E. N., Leal M. A., Haubrich R. H., Richie J. A., Edwards J. E., Jr, Ghannoum M. A. Identification of patients with acute AIDS-associated cryptococcal meningitis who can be effectively treated with fluconazole: the role of antifungal susceptibility testing. Clin Infect Dis. 1996 Feb;22(2):322–328. doi: 10.1093/clinids/22.2.322. [DOI] [PubMed] [Google Scholar]
  30. 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]

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