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. 1997 Jul;41(7):1455–1459. doi: 10.1128/aac.41.7.1455

Efficacy of D0870 treatment of experimental Candida vaginitis.

P L Fidel Jr 1, J L Cutright 1, J D Sobel 1
PMCID: PMC163939  PMID: 9210665

Abstract

In this study, oral administration of the triazole D0870 was compared to oral administration of fluconazole in the treatment of experimental vaginal candidiasis. With an estrogen-dependent murine model of Candida albicans vaginal infection, the effects of D0870 on several isolates, including fluconazole-susceptible and -resistant isolates, were tested. D0870, at doses of 0.5 and 2.5 mg/kg of body weight given once over the course of a 10-day infection, was effective in eradicating vaginitis caused by fluconazole-susceptible laboratory and clinical isolates, respectively. In contrast, a stricter treatment regimen (every 24 to 48 h) with 10 and 25 mg of fluconazole per kg was required to achieve similar reductions in vaginal fungal titers induced by the same isolates. Whereas fluconazole was consistently ineffective in infections induced by fluconazole-resistant isolates, as predicted by in vitro susceptibility tests, D0870 was effective, although a daily regimen of 25 mg/kg was required. Additional studies showed that despite the in vitro activity of D0870 against two clinical Candida glabrata isolates, neither D0870 nor fluconazole was effective at daily doses as high as 100 and 125 mg/kg, respectively. Taken together, although D0870 failed to show efficacy against experimental C. glabrata vaginitis, D0870 was superior to fluconazole in the treatment of experimental C. albicans vaginitis caused by isolates that were either susceptible or resistant to fluconazole.

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Selected References

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  1. Arilla M. C., Carbonero J. L., Schneider J., Regúlez P., Quindós G., Pontón J., Cisterna R. Vulvovaginal candidiasis refractory to treatment with fluconazole. Eur J Obstet Gynecol Reprod Biol. 1992 Mar 23;44(1):77–80. doi: 10.1016/0028-2243(92)90317-r. [DOI] [PubMed] [Google Scholar]
  2. Bart-Delabesse E., Boiron P., Carlotti A., Dupont B. Candida albicans genotyping in studies with patients with AIDS developing resistance to fluconazole. J Clin Microbiol. 1993 Nov;31(11):2933–2937. doi: 10.1128/jcm.31.11.2933-2937.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Case C. P., MacGowan A. P., Brown N. M., Reeves D. S., Whitehead P., Felmingham D. Prophylactic oral fluconazole and candida fungaemia. Lancet. 1991 Mar 30;337(8744):790–790. doi: 10.1016/0140-6736(91)91406-k. [DOI] [PubMed] [Google Scholar]
  4. Clemons K. V., Hanson L. H., Stevens D. A. Activities of the triazole D0870 in vitro and against murine blastomycosis. Antimicrob Agents Chemother. 1993 May;37(5):1177–1179. doi: 10.1128/aac.37.5.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clemons K. V., Stevens D. A. Efficacy of the triazole D0870 in a murine model of systemic histoplasmosis. Antimicrob Agents Chemother. 1995 Mar;39(3):778–780. doi: 10.1128/AAC.39.3.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clemons K. V., Stevens D. A. Utility of the triazole D0870 in the treatment of experimental systemic coccidioidomycosis. J Med Vet Mycol. 1994;32(4):323–326. doi: 10.1080/02681219480000411. [DOI] [PubMed] [Google Scholar]
  7. Clift R. A. Candidiasis in the transplant patient. Am J Med. 1984 Oct 30;77(4D):34–38. [PubMed] [Google Scholar]
  8. Correa A. L., Velez G., Albert M., Luther M., Rinaldi M. G., Graybill J. R. Comparison of D0870 and fluconazole in the treatment of murine cryptococcal meningitis. J Med Vet Mycol. 1995 Nov-Dec;33(6):367–374. doi: 10.1080/02681219580000721. [DOI] [PubMed] [Google Scholar]
  9. Dunn P. L., North R. J. Resolution of primary murine listeriosis and acquired resistance to lethal secondary infection can be mediated predominantly by Thy-1+ CD4- CD8- cells. J Infect Dis. 1991 Nov;164(5):869–877. doi: 10.1093/infdis/164.5.869. [DOI] [PubMed] [Google Scholar]
  10. Fan-Havard P., Capano D., Smith S. M., Mangia A., Eng R. H. Development of resistance in candida isolates from patients receiving prolonged antifungal therapy. Antimicrob Agents Chemother. 1991 Nov;35(11):2302–2305. doi: 10.1128/aac.35.11.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fidel P. L., Jr, Cutright J. L., Tait L., Sobel J. D. A murine model of Candida glabrata vaginitis. J Infect Dis. 1996 Feb;173(2):425–431. doi: 10.1093/infdis/173.2.425. [DOI] [PubMed] [Google Scholar]
  12. Fidel P. L., Jr, Lynch M. E., Sobel J. D. Candida-specific Th1-type responsiveness in mice with experimental vaginal candidiasis. Infect Immun. 1993 Oct;61(10):4202–4207. doi: 10.1128/iai.61.10.4202-4207.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fidel P. L., Jr, Lynch M. E., Sobel J. D. Candida-specific cell-mediated immunity is demonstrable in mice with experimental vaginal candidiasis. Infect Immun. 1993 May;61(5):1990–1995. doi: 10.1128/iai.61.5.1990-1995.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fleury F. J. Adult vaginitis. Clin Obstet Gynecol. 1981 Jun;24(2):407–438. doi: 10.1097/00003081-198106000-00008. [DOI] [PubMed] [Google Scholar]
  15. Geiger A. M., Foxman B., Sobel J. D. Chronic vulvovaginal candidiasis: characteristics of women with Candida albicans, C glabrata and no candida. Genitourin Med. 1995 Oct;71(5):304–307. doi: 10.1136/sti.71.5.304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Graybill J. R., Najvar L. K., Holmberg J. D., Luther M. F. Fluconazole, D0870, and flucytosine treatment of disseminated Candida tropicalis infections in mice. Antimicrob Agents Chemother. 1995 Apr;39(4):924–929. doi: 10.1128/aac.39.4.924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Humphrey M. J., Jevons S., Tarbit M. H. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985 Nov;28(5):648–653. doi: 10.1128/aac.28.5.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Karabinis A., Hill C., Leclercq B., Tancrède C., Baume D., Andremont A. Risk factors for candidemia in cancer patients: a case-control study. J Clin Microbiol. 1988 Mar;26(3):429–432. doi: 10.1128/jcm.26.3.429-432.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Karyotakis N. C., Dignani M. C., Hachem R., Anaissie E. J. Activities of D0870, a novel triazole, against Candida lusitaniae and Trichosporon beigelii in experimental murine infections. Antimicrob Agents Chemother. 1995 Feb;39(2):571–573. doi: 10.1128/aac.39.2.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Klein R. S., Harris C. A., Small C. B., Moll B., Lesser M., Friedland G. H. Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N Engl J Med. 1984 Aug 9;311(6):354–358. doi: 10.1056/NEJM198408093110602. [DOI] [PubMed] [Google Scholar]
  21. Lynch M. E., Sobel J. D., Fidel P. L., Jr Role of antifungal drug resistance in the pathogenesis of recurrent vulvovaginal candidiasis. J Med Vet Mycol. 1996 Sep-Oct;34(5):337–339. doi: 10.1080/02681219680000571. [DOI] [PubMed] [Google Scholar]
  22. Macher A. M. The pathology of AIDS. Public Health Rep. 1988 May-Jun;103(3):246–254. [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Redondo-Lopez V., Lynch M., Schmitt C., Cook R., Sobel J. D. Torulopsis glabrata vaginitis: clinical aspects and susceptibility to antifungal agents. Obstet Gynecol. 1990 Oct;76(4):651–655. [PubMed] [Google Scholar]
  25. Ruhnke M., Eigler A., Engelmann E., Geiseler B., Trautmann M. Correlation between antifungal susceptibility testing of Candida isolates from patients with HIV infection and clinical results after treatment with fluconazole. Infection. 1994 Mar-Apr;22(2):132–136. doi: 10.1007/BF01739024. [DOI] [PubMed] [Google Scholar]
  26. Saag M. S., Dismukes W. E. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988 Jan;32(1):1–8. doi: 10.1128/aac.32.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sandven P., Bjørneklett A., Maeland A. Susceptibilities of Norwegian Candida albicans strains to fluconazole: emergence of resistance. The Norwegian Yeast Study Group. Antimicrob Agents Chemother. 1993 Nov;37(11):2443–2448. doi: 10.1128/aac.37.11.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sangeorzan J. A., Bradley S. F., He X., Zarins L. T., Ridenour G. L., Tiballi R. N., Kauffman C. A. Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Am J Med. 1994 Oct;97(4):339–346. doi: 10.1016/0002-9343(94)90300-x. [DOI] [PubMed] [Google Scholar]
  29. Sobel J. D. Management of recurrent vulvovaginal candidiasis with intermittent ketoconazole prophylaxis. Obstet Gynecol. 1985 Mar;65(3):435–440. [PubMed] [Google Scholar]
  30. Sobel J. D. Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann N Y Acad Sci. 1988;544:547–557. doi: 10.1111/j.1749-6632.1988.tb40450.x. [DOI] [PubMed] [Google Scholar]
  31. Sobel J. D., Vazquez J. A. Symptomatic vulvovaginitis due to fluconazole-resistant Candida albicans in a female who was not infected with human immunodeficiency virus. Clin Infect Dis. 1996 Apr;22(4):726–727. doi: 10.1093/clinids/22.4.726. [DOI] [PubMed] [Google Scholar]
  32. Wardle H. M., Law D., Moore C. B., Mason C., Denning D. W. In vitro activity of D0870 compared with those of other azoles against fluconazole-resistant Candida spp. Antimicrob Agents Chemother. 1995 Apr;39(4):868–871. doi: 10.1128/aac.39.4.868. [DOI] [PMC free article] [PubMed] [Google Scholar]

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