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Antimicrobial Agents and Chemotherapy, May 2007, p. 1616-1620, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00105-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vivo Efficacy of Anidulafungin and Caspofungin against Candida glabrata and Association with In Vitro Potency in the Presence of Sera{triangledown}

Nathan P. Wiederhold,1,2* Laura K. Najvar,2 Rosie Bocanegra,2 Destiny Molina,2 Marcos Olivo,2 and John R. Graybill2

College of Pharmacy, The University of Texas at Austin, Austin, Texas,1 Department of Medicine/Infectious Diseases, The University of Texas Health Science Center at San Antonio, San Antonio, Texas2

Received 24 January 2007/ Returned for modification 30 January 2007/ Accepted 12 February 2007

In vitro studies have demonstrated that anidulafungin has greater potency than caspofungin against Candida glabrata. However, data from in vivo studies demonstrating that it has superior efficacy are lacking. The objective of this study was to compare the activities of anidulafungin and caspofungin against C. glabrata in a murine model of disseminated candidiasis. Two clinical C. glabrata isolates were used, including one with reduced caspofungin susceptibility. MICs were determined by broth microdilution in the presence and absence of sera. For the animal studies, mice were immunosuppressed with 5-fluorouracil one day prior to intravenous inoculation. Treatment with anidulafungin and caspofungin (0, 0.5, 1, 5, and 10 mg/kg of body weight per day) was begun 24 h later and was continued through day 7 postinoculation. The CFU were enumerated from kidney tissue. According to the standard microdilution methodology, anidulafungin had superior in vitro activity. However, this enhanced potency was attenuated by the addition of mouse and human sera. Caspofungin reduced the kidney fungal burden at lower doses compared to that achieved with anidulafungin in mice infected with the isolate with the lower MIC. Against the strain with the elevated caspofungin MIC, both anidulafungin and caspofungin were effective in reducing the kidney fungal burden at the higher doses studied. Despite the greater in vitro activity of anidulafungin in the absence of sera, both echinocandins were similarly effective in reducing the fungal burden in kidney tissue. The superior in vitro activity of anidulafungin did not confer enhanced in vivo efficacy against C. glabrata.

* Corresponding author. Mailing address: UTHSCSA, PERC, MSC 6220, 7703 Floyd Curl Drive, San Antonio, TX 78229. Phone: (210) 567-8340. Fax: (210) 567-8328. E-mail: wiederholdn{at}uthscsa.edu

{triangledown} Published ahead of print on 16 February 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1616-1620, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.00105-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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