Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs

Kirsten Nielsen; Priya Vedula; Kyle D. Smith; David B. Meya; Edward P. Garvey; William J. Hoekstra; Robert J. Schotzinger; David R Boulware

doi:10.1093/mmy/myw089

Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs

Kirsten Nielsen, Priya Vedula, Kyle D. Smith, David B. Meya, Edward P. Garvey, William J. Hoekstra, Robert J. Schotzinger, David R Boulware

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16-32 μg/ml) or resistant (MIC ≥ 64 μg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 μg/ml. The VT-1129 MIC50 was 0.05 μg/ml and 0.25 μg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.

Original language	English (US)
Pages (from-to)	453-456
Number of pages	4
Journal	Medical mycology
Volume	55
Issue number	4
DOIs	https://doi.org/10.1093/mmy/myw089
State	Published - Jun 1 2017

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Publisher Copyright:
© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Keywords

CYP51
Cryptococcus
VT-1129
antifungal
azole

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title = "Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs",

abstract = "Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16-32 μg/ml) or resistant (MIC ≥ 64 μg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 μg/ml. The VT-1129 MIC50 was 0.05 μg/ml and 0.25 μg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.",

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doi = "10.1093/mmy/myw089",

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AU - Nielsen, Kirsten

AU - Vedula, Priya

AU - Smith, Kyle D.

AU - Meya, David B.

AU - Garvey, Edward P.

AU - Hoekstra, William J.

AU - Schotzinger, Robert J.

AU - Boulware, David R

N1 - Publisher Copyright: © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16-32 μg/ml) or resistant (MIC ≥ 64 μg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 μg/ml. The VT-1129 MIC50 was 0.05 μg/ml and 0.25 μg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.

AB - Although antifungal drug resistance in the human fungal pathogen Cryptococcus neoformans is relatively uncommon, fluconazole-resistant strains are problematic for preemptive treatment of cryptococcal antigenemia or during cryptococcal meningitis consolidation therapy. We analyzed activity of the experimental antifungal VT-1129 on 51 clinical Cryptococcus neoformans isolates previously screened for fluconazole resistance; with an emphasis on fluconazole dose-dependent (MIC 16-32 μg/ml) or resistant (MIC ≥ 64 μg/ml) isolates. Overall, the VT-1129 geometric mean MIC was 0.027 μg/ml. The VT-1129 MIC50 was 0.05 μg/ml and 0.25 μg/ml for dose-dependent (n = 27) and resistant isolates (n = 6), respectively. These data suggest VT-1129 shows potential for use against fluconazole-resistant Cryptococcus.

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KW - azole

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Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs

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