PhD Scientific Days 2020

Pharmaceutical Sciences II. Lectures

In vitro and In Vivo Efficacy of Amphotericin B against Candida Auris Isolates

Előadó neve

Tóth, Zoltán, MSc

Előadó munkahelye

Department of Medical Microbiology, Faculty of Medicine, University of Debrecen

Előadó telefonszáma

+36206183086

Előadó e-mail címe

toth.zoltan@med.unideb.hu

Az előadás címe

In vitro and In Vivo Efficacy of Amphotericin B against Candida Auris Isolates

Szerző(k) neve és munkahelye

Zoltán Tóth1,2, Lajos Forgács1,2, Fruzsina Nagy1,2, Bence Balázs1,2, Renátó Kovács1, Gábor Kardos1, László Majoros1

1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen
2 Doctoral School of Pharmaceutical Sciences, University of Debrecen

Szekció

Pharmaceutical Sciences II. Lectures

Language of the presentation

Hungarian

Section, first choice

Pharmaceutical Sciences

Section, second choice

Pharmaceutical Sciences

Összefoglaló szövege

C. auris is a recently emerged fungal pathogen associated with hospital outbreaks and high mortality. Similarly to other pathogenic fungi, therapeutic options are very limited and antifungal resistance commonly found for C. auris further aggravates treatment. While amphotericin B is not the drug of choice for invasive Candida infections, it may be the last resort antifungal against echinocandin resistant C. auris isolates or in cases of central nervous or urinary tract involvement.
Aim of our study was to examine the pharmacodynamic activity of amphotericin B against different C. auris lineages.
In our experiments the in vitro activity of amphotericin B was assessed with time-kill methodology on clinically relevant concentrations (0,25, 0,5, 1, 2 mg/l) against nine C. auris isolates belonging to three different lineages (South-Asian, South-African, South American). In vivo efficacy was determined in tissue fungal burden experiments, performed in a neutropenic C. auris bloodstream infection mouse model against six isolates. Daily amphotericin B treatment (1 mg/kg) of the animals was started one day postinfection and continued for five days. Residual fungal cells in the kidneys of treated and control animals were compared using Mann-Whitney test at day six postinfection.
According to our results, amphotericin B exerted fungistatic activity against most of the isolates at concentrations between 0,25-1 mg/l while was fungicidal at 2 mg/l in vitro against six out of nine isolates tested. A high degree of variance in activity was observed against South-Asian isolates, while was comparable for the other two clades. Daily administration of 1 mg/kg resulted in significantly decreased kidney fungal burden compared to control at day six, however the activity was only fungistatic and while difference was significant, never exceeded two orders of magnitude. The better the in vitro activity was, the higher decrease in fungal burden was observed during in vivo experiments.
Based on our results in vitro activity of amphotericin B at 1 mg/l correlates best with the in vivo efficacy. While a significant decrease in fungal burden was observed, the slow elimination of fungal cells may necessitate a longer than standard course of amphotericin B treatment.

Additional Information

Zoltán Tóth, Fruzsina Nagy, Bence Balázs were supported by the ÚNKP-19-3 New National Excellence Program of the Ministry for Innovation and Technology

Zoltán Tóth, Fruzsina Nagy, Bence Balázs were supported by the EFOP-3.6.3-VEKOP-16-2017-00009 Program

Supervisor: Renátó Kovács
kovacs.renato@med.unideb.hu

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4739

Start

12:10

End

12:25

Authors (legacy)

Zoltán Tóth1,2, Lajos Forgács1,2, Fruzsina Nagy1,2, Bence Balázs1,2, Renátó Kovács1, Gábor Kardos1, László Majoros1

1 Department of Medical Microbiology, Faculty of Medicine, University of Debrecen
2 Doctoral School of Pharmaceutical Sciences, University of Debrecen