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1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris

BACKGROUND: Candida auris is an emerging multiresistant nosocomial pathogen responsible for outbreaks around the world. It is associated with therapeutic failure and high mortality rates. Echinocandins are the empiric treatment choice for C. auris infections. However, clinical reports show that some...

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Autores principales: Dudiuk, Catiana, Berrio, Indira, Theill, Laura, Morales-Lopez, Soraya, Salcedo, Soraya, Rodriguez, Jose, Gamarra, Soledad, Garcia-Effron, Guillermo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253957/
http://dx.doi.org/10.1093/ofid/ofy210.1243
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author Dudiuk, Catiana
Berrio, Indira
Theill, Laura
Morales-Lopez, Soraya
Salcedo, Soraya
Rodriguez, Jose
Gamarra, Soledad
Garcia-Effron, Guillermo
author_facet Dudiuk, Catiana
Berrio, Indira
Theill, Laura
Morales-Lopez, Soraya
Salcedo, Soraya
Rodriguez, Jose
Gamarra, Soledad
Garcia-Effron, Guillermo
author_sort Dudiuk, Catiana
collection PubMed
description BACKGROUND: Candida auris is an emerging multiresistant nosocomial pathogen responsible for outbreaks around the world. It is associated with therapeutic failure and high mortality rates. Echinocandins are the empiric treatment choice for C. auris infections. However, clinical reports show that some patients respond poorly to this therapy. The aim of this study was to determine the in vitro activity of Caspofungin and Anidulafungin against C. auris by time–kill curves method. METHODS: Twenty C. auris strains were studied. They were isolated from patients with proven invasive fungal infection. Susceptibility testing was performed following the Clinical and Laboratory Standards Institute (CLSI) M27-A3 and S4 documents. Time-killing experiments were conducted for 10 of the 20 isolates (in duplicate on 2 separate days) using RPMI-1640 buffered with MOPS. Caspofungin and anidulafungin tested concentrations were 0.12, 0.25, 0.50, 1.00 and 8.00 µg/mL. The inoculum was adjusted to 1 × 10(5) CFU/mL using a Neubauer chamber. A 0.05 mL aliquot of each dilution was taken at different time points (0, 2, 4, 6, 8, 10, 24 and 48 hours). These aliquots were serially diluted in sterile water, spread onto Sabouraud plates and incubated at 35°C to determine the numbers of CFU per milliliter. The killing kinetics and the fungicidal activity were analyzed by fitting the mean data at each time point to an exponential equation: N(t) = N(0) × e(−kt) (N(t) viable yeasts at time t; N(0) starting inoculum; K killing rate; t incubation time). RESULTS: Anidulafungin and caspofungin MICs geometric means were 1.68 µg/mL (range: 0.5–8.0 µg/mL) and 2.55 µg/mL (range 0.25–8.0 μg/mL), respectively. None of the drugs were able to reach fungicidal activity (no 99.9% inhibition). The mean time to reach 50% growth reduction were 1.74 ± 0.45 hours and 5.30 ± 2.81 hours for the MIC values of each strain for anidulafungin and caspofungin, respectively CONCLUSION: The tested echinocandins showed no in vitro fungicidal activity against C. auris at concentrations reached in serum despite strain’s MICs. Caspofungin exhibited a significant lowest killing rate. DISCLOSURES: All authors: No reported disclosures.
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spelling pubmed-62539572018-11-28 1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris Dudiuk, Catiana Berrio, Indira Theill, Laura Morales-Lopez, Soraya Salcedo, Soraya Rodriguez, Jose Gamarra, Soledad Garcia-Effron, Guillermo Open Forum Infect Dis Abstracts BACKGROUND: Candida auris is an emerging multiresistant nosocomial pathogen responsible for outbreaks around the world. It is associated with therapeutic failure and high mortality rates. Echinocandins are the empiric treatment choice for C. auris infections. However, clinical reports show that some patients respond poorly to this therapy. The aim of this study was to determine the in vitro activity of Caspofungin and Anidulafungin against C. auris by time–kill curves method. METHODS: Twenty C. auris strains were studied. They were isolated from patients with proven invasive fungal infection. Susceptibility testing was performed following the Clinical and Laboratory Standards Institute (CLSI) M27-A3 and S4 documents. Time-killing experiments were conducted for 10 of the 20 isolates (in duplicate on 2 separate days) using RPMI-1640 buffered with MOPS. Caspofungin and anidulafungin tested concentrations were 0.12, 0.25, 0.50, 1.00 and 8.00 µg/mL. The inoculum was adjusted to 1 × 10(5) CFU/mL using a Neubauer chamber. A 0.05 mL aliquot of each dilution was taken at different time points (0, 2, 4, 6, 8, 10, 24 and 48 hours). These aliquots were serially diluted in sterile water, spread onto Sabouraud plates and incubated at 35°C to determine the numbers of CFU per milliliter. The killing kinetics and the fungicidal activity were analyzed by fitting the mean data at each time point to an exponential equation: N(t) = N(0) × e(−kt) (N(t) viable yeasts at time t; N(0) starting inoculum; K killing rate; t incubation time). RESULTS: Anidulafungin and caspofungin MICs geometric means were 1.68 µg/mL (range: 0.5–8.0 µg/mL) and 2.55 µg/mL (range 0.25–8.0 μg/mL), respectively. None of the drugs were able to reach fungicidal activity (no 99.9% inhibition). The mean time to reach 50% growth reduction were 1.74 ± 0.45 hours and 5.30 ± 2.81 hours for the MIC values of each strain for anidulafungin and caspofungin, respectively CONCLUSION: The tested echinocandins showed no in vitro fungicidal activity against C. auris at concentrations reached in serum despite strain’s MICs. Caspofungin exhibited a significant lowest killing rate. DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2018-11-26 /pmc/articles/PMC6253957/ http://dx.doi.org/10.1093/ofid/ofy210.1243 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Dudiuk, Catiana
Berrio, Indira
Theill, Laura
Morales-Lopez, Soraya
Salcedo, Soraya
Rodriguez, Jose
Gamarra, Soledad
Garcia-Effron, Guillermo
1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris
title 1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris
title_full 1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris
title_fullStr 1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris
title_full_unstemmed 1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris
title_short 1412. Caspofungin and Anidulafungin Behave as Fungistatic Agents Against Candida auris
title_sort 1412. caspofungin and anidulafungin behave as fungistatic agents against candida auris
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253957/
http://dx.doi.org/10.1093/ofid/ofy210.1243
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