Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection

Alexander J Lepak; Miao Zhao; Elizabeth L Berkow; Shawn R Lockhart; David R Andes

doi:10.1128/AAC.00791-17

Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection

Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00791-17. doi: 10.1128/AAC.00791-17. Print 2017 Aug.

Authors

Alexander J Lepak¹, Miao Zhao^{1

2}, Elizabeth L Berkow³, Shawn R Lockhart³, David R Andes^{4

2}

Affiliations

¹ Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
² Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA.
³ Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁴ Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA [email protected].

Abstract

Candida auris is an emerging multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine C. auris strains was explored using a murine invasive candidiasis model. The total drug median pharmacodynamic (PD) target associated with net stasis was a fluconazole AUC/MIC (the area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 26, an amphotericin B C_max/MIC (maximum concentration of drug in serum divided by the MIC) of 0.9, and a micafungin AUC/MIC of 54. The micafungin PD targets for C. auris were ≥20-fold lower than those of other Candida species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes.

Keywords: C. auris; antifungal resistance; antifungal therapy; pharmacodynamics.

MeSH terms

Amphotericin B / blood
Amphotericin B / pharmacokinetics*
Amphotericin B / therapeutic use*
Animals
Antifungal Agents / blood
Antifungal Agents / pharmacokinetics
Antifungal Agents / therapeutic use*
Candida / drug effects*
Candida / isolation & purification
Candida / pathogenicity
Candidiasis / drug therapy*
Candidiasis / microbiology
Candidiasis, Invasive / drug therapy*
Candidiasis, Invasive / microbiology
Disease Models, Animal
Drug Resistance, Multiple, Fungal
Echinocandins / blood
Echinocandins / pharmacokinetics*
Echinocandins / therapeutic use*
Fluconazole / blood
Fluconazole / pharmacokinetics*
Fluconazole / therapeutic use*
Humans
Lipopeptides / blood
Lipopeptides / pharmacokinetics*
Lipopeptides / therapeutic use*
Micafungin
Mice
Microbial Sensitivity Tests

Substances

Antifungal Agents
Echinocandins
Lipopeptides
Amphotericin B
Fluconazole
Micafungin

Supplementary concepts

Systemic candidiasis