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. 1994 Jul;38(7):1604–1607. doi: 10.1128/aac.38.7.1604

Treatment of disseminated Torulopsis glabrata infection with DO870 and amphotericin B.

B A Atkinson 1, R Bocanegra 1, A L Colombo 1, J R Graybill 1
PMCID: PMC284599  PMID: 7979293

Abstract

Torulopsis glabrata, an opportunist pathogen in immunosuppressed patients, is resistant to many antifungal agents, and there are no established treatment regimens for this organism. The mouse model was used to evaluate treatment with DO870, amphotericin B, fluconazole, and their combination. Mice were immunosuppressed with 5 mg of gold sodium thiomalate given intraperitoneally 1 day prior to intravenous infection with 10(8) T. glabrata cells. Treatment with a new antifungal triazole, DO870, at doses ranging from 1 to 50 mg/kg of body weight administered per os either daily or on alternate days; fluconazole at 100 mg/kg twice a day per os; or amphotericin B at 3 mg/kg/day intraperitoneally was begun 1 day after infection. Treatment for 5 days was followed by sacrifice 2 days later for determining CFU counts in spleen and kidney tissue. For a fluconazole-sensitive isolate (MIC of DO870, < 1.25 micrograms/ml), DO870 at 5 mg/kg/day significantly reduced counts in kidney and spleen tissue (P < 0.05), amphotericin B was modestly effective, and the combination of DO870 (25 mg/kg) and amphotericin B (3 mg/kg) was markedly more effective than either drug alone (P < 0.01). Three additional isolates were resistant in vitro to DO870 (MIC, 4 micrograms/ml). No reduction in CFU in kidney or spleen tissue was observed with DO870 when compared with counts in control tissue. DO870 is effective in vivo against at least some isolates of T. glabrata and when combined with amphotericin B can exert additive effects.

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Selected References

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  1. Bodey G. P. Candidiasis in cancer patients. Am J Med. 1984 Oct 30;77(4D):13–19. [PubMed] [Google Scholar]
  2. Fraser V. J., Jones M., Dunkel J., Storfer S., Medoff G., Dunagan W. C. Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis. 1992 Sep;15(3):414–421. doi: 10.1093/clind/15.3.414. [DOI] [PubMed] [Google Scholar]
  3. Jessop J. D., Vernon-Roberts B., Harris J. Effects of gold salts and prednisolone on inflammatory cells. I. Phagocytic activity of macrophages and polymorphs in inflammatory exudates studied by a "skin-window" technique in rheumatoid and control patients. Ann Rheum Dis. 1973 Jul;32(4):294–300. doi: 10.1136/ard.32.4.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Karyotakis N. C., Anaissie E. J., Hachem R., Dignani M. C., Samonis G. Comparison of the efficacy of polyenes and triazoles against hematogenous Candida krusei infection in neutropenic mice. J Infect Dis. 1993 Nov;168(5):1311–1313. doi: 10.1093/infdis/168.5.1311. [DOI] [PubMed] [Google Scholar]
  5. Kowanko I. C., Ferrante A., Harvey D. P., Carman K. L. Granulocyte-macrophage colony-stimulating factor augments neutrophil killing of Torulopsis glabrata and stimulates neutrophil respiratory burst and degranulation. Clin Exp Immunol. 1991 Feb;83(2):225–230. doi: 10.1111/j.1365-2249.1991.tb05619.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kullberg B. J., van 't Wout J. W., Poell R. J., van Furth R. Combined effect of fluconazole and recombinant human interleukin-1 on systemic candidiasis in neutropenic mice. Antimicrob Agents Chemother. 1992 Jun;36(6):1225–1229. doi: 10.1128/aac.36.6.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Meunier-Carpentier F., Kiehn T. E., Armstrong D. Fungemia in the immunocompromised host. Changing patterns, antigenemia, high mortality. Am J Med. 1981 Sep;71(3):363–370. doi: 10.1016/0002-9343(81)90162-5. [DOI] [PubMed] [Google Scholar]
  8. Peng T., Galgiani J. N. In vitro studies of a new antifungal triazole, D0870, against Candida albicans, Cryptococcus neoformans, and other pathogenic yeasts. Antimicrob Agents Chemother. 1993 Oct;37(10):2126–2131. doi: 10.1128/aac.37.10.2126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Persellin R. H., Ziff M. The effect of gold salt on lysosomal enzymes of the peritoneal macrophage. Arthritis Rheum. 1966 Feb;9(1):57–65. doi: 10.1002/art.1780090107. [DOI] [PubMed] [Google Scholar]
  10. van't Wout J. W., Linde I., Leijh P. C., van Furth R. Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritoneal leukocytes in mice under normal conditions and during acute inflammatory reaction. Inflammation. 1989 Feb;13(1):1–14. doi: 10.1007/BF00918959. [DOI] [PubMed] [Google Scholar]

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