Catiana Dudiuk1,2, Indira Berrio3,4, Florencia Leonardelli1,2, Soraya Morales-Lopez5,6, Laura Theill1, Daiana Macedo1,2, José Yesid-Rodriguez7, Soraya Salcedo8, Adriana Marin8, Soledad Gamarra1, Guillermo Garcia-Effron1,2. 1. Laboratorio de Micología y Diagnóstico Molecular, Cátedra de Parasitología y Micología, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina. 2. Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), CCT, Santa Fe, Argentina. 3. Medical and Experimental Mycology Group, Corporación para Investigaciones Biológicas (CIB), Medellín, Colombia. 4. Hospital general de Medellin 'Luz Castro de Gutiérrez' ESE, Medellín, Colombia. 5. Universidad de Santander, Facultad de Ciencias de la Salud, Grupo de Investigación CIENCIA UDES, Valledupar, Colombia. 6. Laboratorios Nancy Flórez García S.A.S., Valledupar, Colombia. 7. Centro de Investigaciones Microbiológicas del Cesar, CIMCE, Valledupar, Colombia. 8. Clínica General del Norte, Barranquilla, Colombia.
Abstract
BACKGROUND: Candida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking. OBJECTIVES: Our aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time-kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species. METHODS: The susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose-response and time-kill patterns were determined. RESULTS: Echinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively). CONCLUSIONS: Amphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.
BACKGROUND:Candida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking. OBJECTIVES: Our aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time-kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species. METHODS: The susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose-response and time-kill patterns were determined. RESULTS:Echinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively). CONCLUSIONS:Amphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.
Authors: Zoltán Papp; Andrew M Borman; Lajos Forgács; Renátó Kovács; Zoltán Tóth; Chiu Chun-Ju; Gábor Kardos; Béla Juhász; Judit Szilvássy; László Majoros Journal: Pathogens Date: 2021-08-06
Authors: Lajos Forgács; Andrew M Borman; Renátó Kovács; Dávid Balázsi; Zoltán Tóth; Bence Balázs; Chiu Chun-Ju; Gábor Kardos; Ilona Kovacs; László Majoros Journal: J Fungi (Basel) Date: 2022-05-11
Authors: Zoltán Tóth; Lajos Forgács; Tamás Kardos; Renátó Kovács; Jeffrey B Locke; Gábor Kardos; Fruzsina Nagy; Andrew M Borman; Awid Adnan; László Majoros Journal: J Fungi (Basel) Date: 2020-08-17
Authors: Renátó Kovács; Zoltán Tóth; Jeffrey B Locke; Lajos Forgács; Gábor Kardos; Fruzsina Nagy; Andrew M Borman; László Majoros Journal: Microorganisms Date: 2021-04-16