These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Efungumab and caspofungin: pre-clinical data supporting synergy.
    Author: Hodgetts S, Nooney L, Al-Akeel R, Curry A, Awad S, Matthews R, Burnie J.
    Journal: J Antimicrob Chemother; 2008 May; 61(5):1132-9. PubMed ID: 18299636.
    Abstract:
    OBJECTIVES: Heat shock protein 90 (hsp90) is targeted by the humoral response in invasive candidiasis. This paper tests for synergy between caspofungin and efungumab--a human antibody fragment against hsp90. METHODS: The MIC-0, MIC-2 values and FICI were determined for a range of yeasts against efungumab and caspofungin. These yeasts were injected intravenously into mice with: 100 microL of saline plus 100 microL of formulation buffer; 100 microL of caspofungin (1 or 4 mg/kg) plus 100 microL of formulation buffer; or 100 microL of caspofungin (1 or 4 mg/kg) plus 100 microL of efungumab 2 mg/kg. Yeast counts were determined for kidney, liver and spleen. Electron microscopy was performed on efungumab-stained Candida grown with and without caspofungin. RESULTS: The FICIs of efungumab and caspofungin at MIC-0 and MIC-2, respectively, were: fluconazole-susceptible Candida albicans: 0.5, 0.52; fluconazole-resistant C. albicans, Candida tropicalis and Candida krusei: 0.5, 0.5; Candida parapsilosis: 2, 0.5; Candida glabrata: 0.26, 0.28; and Candida guilliermondii: 2, 0.27. A statistically significant reduction in colony counts or increase in the number of negative biopsies (P < 0.05) was seen in mice on combination therapy at 1 mg/kg caspofungin for the renal biopsies of C. glabrata, liver biopsies of fluconazole-resistant C. albicans, C. krusei and C. guilliermondii and spleen biopsies of C. guilliermondii, and at 4 mg/kg for the renal biopsies of C. tropicalis, the liver biopsies of C. parapsilosis and the spleen biopsies of C. guilliermondii and C. glabrata. Electron microscopy confirmed extracellular hsp90 up-regulated by growth in caspofungin. CONCLUSIONS: Efungumab increased the susceptibility of Candida to caspofungin.
    [Abstract] [Full Text] [Related] [New Search]