In Vivo Efficacy of Amphotericin B against Four Candida auris Clades

Lajos Forgács, Andrew M. Borman, Renátó Kovács, Dávid Balázsi, Zoltán Tóth, Bence Balázs, Chiu Chun-Ju, Gábor Kardos, Ilona Kovacs, László Majoros*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p < 0.01), kidneys (p < 0.01) and brain (p < 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system.

Original languageEnglish
Article number499
JournalJournal of Fungi
Volume8
Issue number5
DOIs
Publication statusPublished - May 2022
Externally publishedYes

Bibliographical note

Funding Information:
Funding: R. Kovács was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences. This research was supported by the Hungarian National Research, Development and Innovation Office (NKFIH FK138462). R. Kovács was supported by the UNKP-21-5-473 New National Excellence Program of the Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation Fund.

Funding Information:
Conflicts of Interest: L. Majoros has received conference travel grants from MSD, Cidara, Astellas and Pfizer.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • amphotericin B
  • Candida auris
  • histopathology
  • in vivo
  • mouse

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