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Antimicrobial Agents and Chemotherapy, May 2002, p. 1240-1245, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1240-1245.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Efficacies of Fluconazole, Caspofungin, and Amphotericin B in Candida glabrata-Infected p47phox-/- Knockout Mice

Justina Y. Ju,1 Cynthia Polhamus,1 Kieren A. Marr,2 Steven M. Holland,3 and John E. Bennett1*

Clinical Mycology Section, Laboratory of Clinical Investigation,1 Laboratory of Host Defense, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,3 Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington 981092

Received 24 August 2001/ Returned for modification 10 October 2001/ Accepted 22 January 2002

Candida glabrata is the second leading cause of adult candidemia, resulting in high mortality. Amphotericin B is considered the treatment of choice, while the efficacy of fluconazole is controversial and caspofungin efficacy is unknown. To ascertain drug efficacy in vivo, the utility of a murine model of C. glabrata infection was investigated. C. glabrata was found to cause progressive, lethal infection when injected intravenously into C57BL/6 mice with reduced oxidative microbicidal capacity due to knockout of the p47phox gene. Spleen and kidney organ CFU counts were determined in groups of mice 2 days after the mice completed 6 days of daily intraperitoneal drug treatment, which began on the day of infection. Daily injections of fluconazole at 80 mg/kg did not reduce spleen or kidney CFU counts after infection with C. glabrata strains having in vitro fluconazole MICs of 2, 32, or 256 µg/ml compared to saline-treated controls. However, this fluconazole regimen reduced spleen CFU counts in mice infected with Candida albicans, an infection that is known to be responsive to fluconazole. Caspofungin at 5 mg/kg and amphotericin B at 5 mg/kg were both effective in reducing fungal burden in spleens and kidneys of C. glabrata-infected mice. Ten mice treated for 6 days with caspofungin at 1 mg/kg survived for 15 days, though all 10 saline-injected mice died or were so ill that they had to be sacrificed by 96 h postinfection. This murine model provided evidence of the efficacy of amphotericin B and caspofungin but not of fluconazole against C. glabrata infection.

* Corresponding author. Mailing address: Clinical Center, Rm. 11C304, NIH, Bethesda, MD 20892. Phone: (301) 496-3461. Fax: (301) 480-0050. E-mail: jb46y{at}nih.gov.

Antimicrobial Agents and Chemotherapy, May 2002, p. 1240-1245, Vol. 46, No. 5
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.5.1240-1245.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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