In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species

D Andes; D J Diekema; M A Pfaller; J Bohrmuller; K Marchillo; A Lepak

doi:10.1128/AAC.01584-09

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In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species

Journal article

Open access

Peer reviewed

In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species

D Andes, D J Diekema, M A Pfaller, J Bohrmuller, K Marchillo and A Lepak

Antimicrobial agents and chemotherapy, Vol.54(6), pp.2497-2506

06/2010

DOI: 10.1128/AAC.01584-09

PMCID: PMC2876357

PMID: 20385855

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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 microg/ml; caspofungin, 0.03 to 4.0 microg/ml; and micafungin, 0.008 to 1.0 microg/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.

Antifungal Agents - pharmacology

Lipopeptides - pharmacokinetics

Species Specificity

Lipopeptides - pharmacology

Echinocandins - pharmacokinetics

Candidiasis - microbiology

Mice, Inbred ICR

Echinocandins - administration & dosage

Microbial Sensitivity Tests

Candidiasis - metabolism

Kidney - microbiology

Animals

Candida albicans - drug effects

Candidiasis - drug therapy

Antifungal Agents - pharmacokinetics

Protein Binding

Female

Mice

Candida - drug effects

Lipopeptides - administration & dosage

Antifungal Agents - administration & dosage

Echinocandins - pharmacology

Candida glabrata - drug effects

Details

Title: Subtitle: In vivo comparison of the pharmacodynamic targets for echinocandin drugs against Candida species
Creators: D Andes - Department of Medicine and Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53792, USA. dra@medicine.wisc.edu
D J Diekema
M A Pfaller
J Bohrmuller
K Marchillo
A Lepak
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.54(6), pp.2497-2506
DOI: 10.1128/AAC.01584-09
PMID: 20385855
PMCID: PMC2876357
NLM abbreviation: Antimicrob Agents Chemother
ISSN: 1098-6596
eISSN: 1098-6596
Publisher: United States
Language: English
Date published: 06/2010
Academic Unit: Infectious Diseases; Epidemiology; Pathology; Internal Medicine
Record Identifier: 9983986257102771

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