Pharmacodynamic Optimization for the Treatment of Invasive Candida auris Infection
Advanced Search
Select up to three search categories and corresponding keywords using the fields to the right. Refer to the Help section for more detailed instructions.

Search our Collections & Repository

For very narrow results

When looking for a specific result

Best used for discovery & interchangable words

Recommended to be used in conjunction with other fields



Document Data
Clear All
Clear All

For additional assistance using the Custom Query please check out our Help Page


Pharmacodynamic Optimization for the Treatment of Invasive Candida auris Infection

Filetype[PDF-181.06 KB]


  • Alternative Title:
    Open Forum Infect Dis
  • Personal Author:
  • Description:

    Candida auris is an emerging, nosocomial multidrug-resistant threat with high treatment failure rate and mortality. The optimal antifungal agent to use and susceptibility breakpoints are based on limited clinical data.


    Nine clinical C. auris strains were used. MICs were determined by CLSI standards. Drug treatment studies consisted of: fluconazole (FLC) dose range 0.78–200 mg/kg/12 h, micafungin (MFG) dose range 0.3125–80 mg/kg/24 h, or amphotericin B deoxycholate (AMB) dose range 0.0.78–20 mg/kg/24 hours. Plasma PK was previously determined in the murine model for all three drugs. A 96 h neutropenic murine model of invasive candidiasis (IC) was used for all studies. The Emax Hill equation was used to model the dose–response data to PK/PD index AUC/MIC (FLC and MFG) and Cmax/MIC (AMB). The static and 1 log kill doses (when achieved) and the associated PK/PD targets (AUC/MIC or Cmax/MIC) were determined and compared with previous murine IC studies with C. albicans, C. glabrata, and C. parapsilosis.


    MIC range: FLC 2–256 mg/l, MFG 0.125–4 mg/l, and AMB 0.38–6 mg/l. Dose-dependent activity was observed with all three drugs. Net stasis was achieved against seven strains for FLC, eight strains for MFG, and eight strains for AMB. However, MFG performed significantly better than comparators for cidal endpoints. A 1 log kill endpoint was achieved in eight strains for MFG, whereas this endpoint was only achieved in one strain for FLC and three strains for AMB. PK/PD analyses demonstrated a strong relationship between AUC/MIC and treatment outcome for FLC (R2 0.61) and MFG (R2 0.77); and Cmax/MIC and treatment outcome for AMB (R2 0.64). The median static dose and 1 log kill dose (MFG only) and associated AUC/MIC or Cmax/MIC values are shown (Table).


    MFG was the most potent drug over the dose range achieving up to 2 log kill against eight of nine strains. PK/PD targets for C. auris against FLC and AMB were similar to other Candida species; however, MFG targets were ≥20-fold lower than C. albicans, C. glabrata, and C. parapsilosis. Using the median stasis targets and human PK for each drug, resistance thresholds could be 16 mg/l for FLC, 2–4 mg/l for MFG, and 1–2 mg/l for AMB.


    All authors: No reported disclosures.

  • Subjects:
  • Source:
  • Pubmed Central ID:
  • Document Type:
  • Collection(s):
  • Main Document Checksum:
  • Download URL:
  • File Type:

Supporting Files

More +

You May Also Like

Checkout today's featured content at