JAC Advance Access published online on July 25, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn304
Original research |
Evaluation of aminocandin and caspofungin against Candida glabrata including isolates with reduced caspofungin susceptibility
1 Division of Infectious Diseases, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 2 College of Pharmacy, The University of Texas at Austin, Austin, TX, USA 3 Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Received 3 April 2008; returned 2 May 2008; revised 30 June 2008; accepted 3 July 2008
* Correspondence address. Division of Infectious Diseases, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive (MC7881), San Antonio, TX 78229-3900, USA. Tel: +1-210-567-8340; Fax: +1-210-567-8328; E-mail: wiederholdn{at}uthscsa.edu
Background: Aminocandin is an investigational echinocandin with excellent activity against Candida species, including Candida albicans and Candida tropicalis. However, few data are available for this agent versus Candida glabrata. We compared the in vitro potency and in vivo efficacy of aminocandin and caspofungin against clinical isolates of C. glabrata including those with reduced caspofungin susceptibility (MIC > 2 mg/L).
Methods: In vitro activity was assessed using microdilution broth susceptibility testing. Three isolates, one with a low and two with elevated caspofungin MICs, were chosen and mice were infected with C. glabrata followed by a single dose of aminocandin or caspofungin (0.5–100 mg/kg), or daily doses of caspofungin (0.07–14.3 mg/kg) begun 1 day after inoculation. Reduction in fungal burden, assessed in kidney tissue on day 8 post-inoculation, was the marker of antifungal response.
Results: Aminocandin was more potent than caspofungin against each isolate with reduced caspofungin susceptibility. Mice infected with the caspofungin-susceptible isolate had significant decreases in tissue burden with low doses of either drug. Higher single doses of aminocandin (
10 mg/kg) were required to reduce fungal burden against the two isolates with elevated caspofungin MICs. Single dose administration of caspofungin was ineffective against one of these isolates, and higher daily doses were required to reduce fungal burden.
Conclusions: These studies suggest that aminocandin has the potential for extended interval dosing in the treatment of C. glabrata infections caused by susceptible isolates. However, higher doses may be required against isolates with reduced caspofungin susceptibility.
Key Words: echinocandin , candidiasis , murine model