Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabrata-infected p47phox-/- knockout mice

Justina Y. Ju, Cynthia Polhamus, Kieren Marr, Steven M. Holland, John E. Bennett

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1240-1245
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume46
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

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caspofungin
Candida glabrata
Fluconazole
Amphotericin B
Knockout Mice
Spleen
Infection
Kidney
Candidemia
Gene Knockout Techniques
Candida albicans
Inbred C57BL Mouse
Pharmaceutical Preparations
Injections

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabrata-infected p47phox-/- knockout mice. / Ju, Justina Y.; Polhamus, Cynthia; Marr, Kieren; Holland, Steven M.; Bennett, John E.

In: Antimicrobial Agents and Chemotherapy, Vol. 46, No. 5, 2002, p. 1240-1245.

Research output: Contribution to journalArticle

Ju, Justina Y. ; Polhamus, Cynthia ; Marr, Kieren ; Holland, Steven M. ; Bennett, John E. / Efficacies of fluconazole, caspofungin, and amphotericin B in Candida glabrata-infected p47phox-/- knockout mice. In: Antimicrobial Agents and Chemotherapy. 2002 ; Vol. 46, No. 5. pp. 1240-1245.
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