Abstract
Cilofungin has potent in vitro activity against Candida albicans, but previous in vivo models using twice daily intermittent dosing regimens have not consistently demonstrated in vivo efficacy. Because of the pharmacokinetics of cilofungin in rabbits, it has been suggested that administration by continuous intravenous infusion might be more effective. We compared the in vivo efficacy of continuous intravenous infusion of cilofungin with that of amphotericin B in a rabbit model of disseminated candidiasis. Cilofungin prepared as previously described in phosphate-buffered 33% polyethylene glycol was lethal to infected rabbits in this model, as was phosphate-buffered 33% polyethylene glycol alone. In contrast, cilofungin in 26% polyethylene glycol and sterile water administered by continuous intravenous infusion was tolerated by rabbits, was significantly more effective than amphotericin therapy in reducing candida colony counts in kidney tissue, and was as effective as amphotericin therapy in lung and spleen tissue and in cardiac valvular vegetations. The dosage regimen and diluent used in some previous studies may have adversely affected outcome of treatment with cilofungin.
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Selected References
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- Bannatyne R. M., Cheung R., Devlin H. R. Microassay foramphotericin B. Antimicrob Agents Chemother. 1977 Jan;11(1):44–46. doi: 10.1128/aac.11.1.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freedman L. R., Johnson M. L. Experimental endocarditis. IV. Tricuspid and aortic valve infection with Candida albicans in rabbits. Yale J Biol Med. 1972 Apr;45(2):163–175. [PMC free article] [PubMed] [Google Scholar]
- Gordee R. S., Zeckner D. J., Ellis L. F., Thakkar A. L., Howard L. C. In vitro and in vivo anti-Candida activity and toxicology of LY121019. J Antibiot (Tokyo) 1984 Sep;37(9):1054–1065. doi: 10.7164/antibiotics.37.1054. [DOI] [PubMed] [Google Scholar]
- Hanson L. H., Stevens D. A. Evaluation of cilofungin, a lipopeptide antifungal agent, in vitro against fungi isolated from clinical specimens. Antimicrob Agents Chemother. 1989 Aug;33(8):1391–1392. doi: 10.1128/aac.33.8.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang A., Edwards F., Bernard E. M., Armstrong D., Schmitt H. J. In vitro activity of the new semi-synthetic polypeptide cilofungin (LY121019) against Aspergillus and Candida species. Eur J Clin Microbiol Infect Dis. 1990 Sep;9(9):697–699. doi: 10.1007/BF01964276. [DOI] [PubMed] [Google Scholar]
- 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]
- Morrison C. J., Stevens D. A. Comparative effects of cilofungin and amphotericin B on experimental murine candidiasis. Antimicrob Agents Chemother. 1990 May;34(5):746–750. doi: 10.1128/aac.34.5.746. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Padula A., Chambers H. F. Evaluation of cilofungin (LY121019) for treatment of experimental Candida albicans endocarditis in rabbits. Antimicrob Agents Chemother. 1989 Oct;33(10):1822–1823. doi: 10.1128/aac.33.10.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perfect J. R., Hobbs M. M., Wright K. A., Durack D. T. Treatment of experimental disseminated candidiasis with cilofungin. Antimicrob Agents Chemother. 1989 Oct;33(10):1811–1812. doi: 10.1128/aac.33.10.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith K. R., Lank K. M., Cobbs C. G., Cloud G. A., Dismukes W. E. Comparison of cilofungin and amphotericin B for therapy of murine candidiasis. Antimicrob Agents Chemother. 1990 Aug;34(8):1619–1621. doi: 10.1128/aac.34.8.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taft C. S., Stark T., Selitrennikoff C. P. Cilofungin (LY121019) inhibits Candida albicans (1-3)-beta-D-glucan synthase activity. Antimicrob Agents Chemother. 1988 Dec;32(12):1901–1903. doi: 10.1128/aac.32.12.1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walsh T. J., Lee J. W., Kelly P., Bacher J., Lecciones J., Thomas V., Lyman C., Coleman D., Gordee R., Pizzo P. A. Antifungal effects of the nonlinear pharmacokinetics of cilofungin, a 1,3-beta-glucan synthetase inhibitor, during continuous and intermittent intravenous infusions in treatment of experimental disseminated candidiasis. Antimicrob Agents Chemother. 1991 Jul;35(7):1321–1328. doi: 10.1128/aac.35.7.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
