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Antimicrobial Agents and Chemotherapy, April 2006, p. 1293-1297, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1293-1297.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Assessment of the Paradoxical Effect of Caspofungin in Therapy of Candidiasis

Karl V. Clemons,1,2,3* Marife Espiritu,1 Rachana Parmar,1 and David A. Stevens1,2,3

California Institute for Medical Research, San Jose, California 95128,1 Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, California 95128,2 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, California 943053

Received 31 January 2006/ Accepted 4 February 2006

Paradoxical growth of some Candida albicans isolates in the presence of caspofungin (CAS) in vitro has been demonstrated previously. We sought to determine whether a similar phenomenon occurred in vivo. A systemic model of candidiasis was studied in CD-1 mice by intravenous inoculation of different isolates of C. albicans. Infected animals were treated with CAS at various dosages (0.01 to 20 mg/kg) and CFU remaining in the kidneys determined. Four clinical isolates that showed paradoxical growth in vitro and one that did not were tested. Recovery of CFU from the kidneys showed that dosages of CAS at 0.1 mg/kg and above were efficacious in the reduction of C. albicans, but were not curative. Against isolates that show paradoxical growth in vitro, CAS was efficacious, but lacked dose responsiveness above 0.5 mg/kg against three of the four. One isolate, 95-68, showed paradoxical growth in vivo with significantly higher CFU recovered from mice given CAS at 20 mg/kg than those given CAS at 5 mg/kg, but the effect was not reproducible in a subsequent experiment. When CAS was given prophylactically and therapeutically, improved efficacy and cure rate were observed. Overall, these data indicate that CAS is highly efficacious against systemic murine candidiasis and a paradoxical effect was not reproducibly demonstrated in vivo.

* Corresponding author. Mailing address: Division of Infectious Diseases, Santa Clara Valley Medical Center, 751 South Bascom Ave., San Jose, CA 95128. Phone: (408) 998-4557. Fax: (408) 998-2723. E-mail: clemons{at}cimr.org.

Antimicrobial Agents and Chemotherapy, April 2006, p. 1293-1297, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1293-1297.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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