Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 Aug;41(8):1775–1777. doi: 10.1128/aac.41.8.1775

Treatment of murine disseminated candidiasis with L-743,872.

J R Graybill 1, L K Najvar 1, M F Luther 1, A W Fothergill 1
PMCID: PMC164003  PMID: 9257759

Abstract

L-743,872 (M991), which is a pneumocandin derivative, was evaluated in a mouse model of disseminated candidiasis caused by a fluconazole-resistant isolate of Candida albicans. In immunocompetent mice M991 prolonged survival at doses as low as 0.0125 mg/kg of body weight per day. In neutropenic mice 0.05 mg/kg was the lowest effective dose. M991 is a very potent drug for treatment of disseminated candidiasis.

Full Text

The Full Text of this article is available as a PDF (159.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angiolella L., Simonetti N., Cassone A. The lipopeptide antimycotic, cilofungin modulates the incorporation of glucan-associated proteins into the cell wall of Candida albicans. J Antimicrob Chemother. 1994 Jun;33(6):1137–1146. doi: 10.1093/jac/33.6.1137. [DOI] [PubMed] [Google Scholar]
  2. Bartizal K., Abruzzo G., Trainor C., Krupa D., Nollstadt K., Schmatz D., Schwartz R., Hammond M., Balkovec J., Vanmiddlesworth F. In vitro antifungal activities and in vivo efficacies of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991, tetrahydroechinocandin B, and L-687,781, a papulacandin. Antimicrob Agents Chemother. 1992 Aug;36(8):1648–1657. doi: 10.1128/aac.36.8.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bartizal K., Scott T., Abruzzo G. K., Gill C. J., Pacholok C., Lynch L., Kropp H. In vitro evaluation of the pneumocandin antifungal agent L-733560, a new water-soluble hybrid of L-705589 and L-731373. Antimicrob Agents Chemother. 1995 May;39(5):1070–1076. doi: 10.1128/aac.39.5.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fisher M. A., Shen S. H., Haddad J., Tarry W. F. Comparison of in vivo activity of fluconazole with that of amphotericin B against Candida tropicalis, Candida glabrata, and Candida krusei. Antimicrob Agents Chemother. 1989 Sep;33(9):1443–1446. doi: 10.1128/aac.33.9.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Graybill J. R., Najvar L. K., Holmberg J. D., Correa A., Luther M. F. Fluconazole treatment of Candida albicans infection in mice: does in vitro susceptibility predict in vivo response? Antimicrob Agents Chemother. 1995 Oct;39(10):2197–2200. doi: 10.1128/aac.39.10.2197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hall G. S., Myles C., Pratt K. J., Washington J. A. Cilofungin (LY121019), an antifungal agent with specific activity against Candida albicans and Candida tropicalis. Antimicrob Agents Chemother. 1988 Sep;32(9):1331–1335. doi: 10.1128/aac.32.9.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Heinic G. S., Stevens D. A., Greenspan D., MacPhail L. A., Dodd C. L., Stringari S., Strull W. M., Hollander H. Fluconazole-resistant Candida in AIDS patients. Report of two cases. Oral Surg Oral Med Oral Pathol. 1993 Dec;76(6):711–715. doi: 10.1016/0030-4220(93)90039-7. [DOI] [PubMed] [Google Scholar]
  8. Kurtz M. B., Douglas C., Marrinan J., Nollstadt K., Onishi J., Dreikorn S., Milligan J., Mandala S., Thompson J., Balkovec J. M. Increased antifungal activity of L-733,560, a water-soluble, semisynthetic pneumocandin, is due to enhanced inhibition of cell wall synthesis. Antimicrob Agents Chemother. 1994 Dec;38(12):2750–2757. doi: 10.1128/aac.38.12.2750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kurtz M. B., Heath I. B., Marrinan J., Dreikorn S., Onishi J., Douglas C. Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activities against (1,3)-beta-D-glucan synthase. Antimicrob Agents Chemother. 1994 Jul;38(7):1480–1489. doi: 10.1128/aac.38.7.1480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee J. W., Kelly P., Lecciones J., Coleman D., Gordee R., Pizzo P. A., Walsh T. J. Cilofungin (LY121019) shows nonlinear plasma pharmacokinetics and tissue penetration in rabbits. Antimicrob Agents Chemother. 1990 Nov;34(11):2240–2245. doi: 10.1128/aac.34.11.2240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Newman S. L., Flanigan T. P., Fisher A., Rinaldi M. G., Stein M., Vigilante K. Clinically significant mucosal candidiasis resistant to fluconazole treatment in patients with AIDS. Clin Infect Dis. 1994 Oct;19(4):684–686. doi: 10.1093/clinids/19.4.684. [DOI] [PubMed] [Google Scholar]
  12. Persons D. A., Laughlin M., Tanner D., Perfect J., Gockerman J. P., Hathorn J. W. Fluconazole and Candida krusei fungemia. N Engl J Med. 1991 Oct 31;325(18):1315–1315. [PubMed] [Google Scholar]
  13. Redding S., Smith J., Farinacci G., Rinaldi M., Fothergill A., Rhine-Chalberg J., Pfaller M. Resistance of Candida albicans to fluconazole during treatment of oropharyngeal candidiasis in a patient with AIDS: documentation by in vitro susceptibility testing and DNA subtype analysis. Clin Infect Dis. 1994 Feb;18(2):240–242. doi: 10.1093/clinids/18.2.240. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Rex J. H., Rinaldi M. G., Pfaller M. A. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother. 1995 Jan;39(1):1–8. doi: 10.1128/aac.39.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rouse M. S., Tallan B. M., Steckelberg J. M., Henry N. K., Wilson W. R. Efficacy of cilofungin therapy administered by continuous intravenous infusion for experimental disseminated candidiasis in rabbits. Antimicrob Agents Chemother. 1992 Jan;36(1):56–58. doi: 10.1128/aac.36.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Van t Wout J. W., Mattie H., van Furth R. Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice. Antimicrob Agents Chemother. 1989 Feb;33(2):147–151. doi: 10.1128/aac.33.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Velez J. D., Allendoerfer R., Luther M., Rinaldi M. G., Graybill J. R. Correlation of in vitro azole susceptibility with in vivo response in a murine model of cryptococcal meningitis. J Infect Dis. 1993 Aug;168(2):508–510. doi: 10.1093/infdis/168.2.508. [DOI] [PubMed] [Google Scholar]
  20. White A., Goetz M. B. Azole-resistant Candida albicans: report of two cases of resistance to fluconazole and review. Clin Infect Dis. 1994 Oct;19(4):687–692. doi: 10.1093/clinids/19.4.687. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES