Affiliation:
1. Department of Medicine and Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin
2. Department of Pathology, University of Iowa, Iowa City, Iowa
Abstract
ABSTRACT
Previous pharmacodynamic studies using
in vivo
candidiasis models have demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC is a good descriptor of the echinocandin exposure-response relationship. Further studies investigating the 24-h AUC/MIC target for a stasis endpoint identified free-drug 24-h AUC/MIC against
Candida albicans
and were similar for two echinocandins, anidulafungin and micafungin. The current studies expand investigation of a third echinocandin (caspofungin) and compare the pharmacodynamic target among
C. albicans
,
Candida glabrata
, and
Candida parapsilosis
. Treatment studies were conducted with six
C. albicans
, nine
C. glabrata
, and 15
C. parapsilosis
strains with various MICs (anidulafungin, 0.015 to 4.0 μg/ml; caspofungin, 0.03 to 4.0 μg/ml; and micafungin, 0.008 to 1.0 μg/ml). Efficacy was closely tied to MIC and the 24-h AUC/MIC. Therapy against
C. parapsilosis
required more of each echinocandin on a mg/kg basis. Caspofungin required less drug on a mg/kg basis for efficacy against all of the organisms than did the other two drugs. However, the 24-h AUC/MIC targets were similar among the echinocandins when free drug concentrations were considered, suggesting the relevance of protein binding. The targets for
C. parapsilosis
(mean, 7) and
C. glabrata
(mean, 7) were significantly lower than those for
C. albicans
(mean, 20) for each echinocandin. The results suggest that current susceptibility breakpoints and the consideration of organism species in these determinations should be reexplored.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
195 articles.
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