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Antimicrobial Agents and Chemotherapy, September 2005, p. 3616-3623, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3616-3623.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Caspofungin Susceptibility Testing of Isolates from Patients with Esophageal Candidiasis or Invasive Candidiasis: Relationship of MIC to Treatment Outcome

Nicholas Kartsonis,* John Killar, Lori Mixson, Chao-Min Hoe, Carole Sable, Kenneth Bartizal, and Mary Motyl

Merck Research Laboratories, West Point, Pennsylvania

Received 12 April 2005/ Returned for modification 16 May 2005/ Accepted 28 June 2005

The caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidiasis and two studies of invasive candidiasis. The MICs of caspofungin for all baseline isolates were measured at a central laboratory using NCCLS criteria (document M-27A); MICs for caspofungin were defined as the lowest concentration inhibiting prominent growth at 24 h. MICs were then compared to clinical and microbiological outcomes across the two diseases. Susceptibility testing for caspofungin was performed on 515 unique baseline isolates of Candida spp. obtained from patients with esophageal candidiasis. MICs for caspofungin ranged from 0.008 to 4 µg/ml; the MIC50 and MIC90 were 0.5 and 1.0 µg/ml, respectively. Susceptibility testing was also performed on 231 unique baseline isolates of Candida spp. from patients with invasive candidiasis. The majority (~96%) of MICs were between 0.125 and 2 µg/ml, with MIC50 and MIC90 for caspofungin being 0.5 and 2.0 µg/ml, respectively. Overall, caspofungin demonstrated potent in vitro activity against clinical isolates of Candida species. A relationship between MIC for caspofungin and treatment outcome was not seen for patients with either esophageal candidiasis or invasive candidiasis. Patients with isolates for which the MICs were highest (>2 µg/ml) had better outcomes than patients with isolates for which the MICs were lower (<1 µg/ml). Additionally, no correlation between MIC and outcome was identified for specific Candida species.

* Corresponding author. Mailing address: Merck Research Laboratories, Merck & Co., Inc., BL 3-4, P.O. Box 4, West Point, PA 19486-0004. Phone: (484) 344-7301. Fax: (484) 344-3370. E-mail: nicholas_kartsonis{at}merck.com.

Antimicrobial Agents and Chemotherapy, September 2005, p. 3616-3623, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3616-3623.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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