Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

Michael A Pfaller; Cecilia Carvalhaes; Shawn A Messer; Paul R Rhomberg; Mariana Castanheira

doi:10.1128/AAC.00099-20

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Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

Journal article

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Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

Michael A Pfaller, Cecilia Carvalhaes, Shawn A Messer, Paul R Rhomberg and Mariana Castanheira

Antimicrobial agents and chemotherapy, Vol.64(4), e00099-20

03/24/2020

DOI: 10.1128/AAC.00099-20

PMCID: PMC7179261

PMID: 32015043

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Abstract

We evaluated the activity of rezafungin and comparators, using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, against a worldwide collection of 2,205 invasive fungal isolates recovered from 2016 to 2018. ( = 1,904 isolates; 6 species), ( = 73), ( = 183), and ( = 45) isolates were tested for their susceptibility (S) to rezafungin as well as the comparators caspofungin, anidulafungin, micafungin, and azoles. Interpretive criteria were applied following CLSI published clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs). Isolates displaying non-wild-type (non-WT) echinocandin MIC values were sequenced for hot spot (HS) mutations. Rezafungin inhibited 99.8% of isolates (MIC , 0.03/0.06 μg/ml), 95.7% of isolates (MIC , 0.06/0.12 μg/ml), 97.4% of isolates (MIC , 0.03/0.06 μg/ml), 100.0% of isolates (MIC , 0.03/0.06 μg/ml), and 100.0% of isolates (MIC , 0.06/0.12 μg/ml) at ≤0.12 μg/ml. All (329/329 [100.0%]) isolates (MIC ,1/2 μg/ml) were inhibited by rezafungin at ≤4 μg/ml. Fluconazole resistance was detected among 8.6% of isolates, 12.5% of isolates, 3.2% of isolates, and 2.6% of isolates. The activity of rezafungin against these 6 spp. was similar to the activity of the other echinocandins. Detection of the HS mutation was performed by sequencing echinocandin-resistant or non-WT isolates. Good activity against was observed for fluconazole and the other azoles, whereas the echinocandins, including rezafungin, displayed limited activity. Rezafungin displayed activity similar to that of the other echinocandins against and These data contribute to accumulating research demonstrating the potential of rezafungin for preventing and treating invasive fungal infections.

Anidulafungin - pharmacology

Antifungal Agents - pharmacology

Aspergillus flavus - drug effects

Aspergillus flavus - isolation & purification

Aspergillus fumigatus - drug effects

Aspergillus fumigatus - isolation & purification

Azoles - pharmacology

Candida - drug effects

Candida - isolation & purification

Caspofungin - pharmacology

Cryptococcus neoformans - drug effects

Cryptococcus neoformans - isolation & purification

Drug Resistance, Fungal - physiology

Echinocandins - pharmacology

Humans

Micafungin - pharmacology

Microbial Sensitivity Tests

Details

Title: Subtitle: Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)
Creators: Michael A Pfaller - University of Iowa
Cecilia Carvalhaes - JMI Laboratories
Shawn A Messer - JMI Laboratories
Paul R Rhomberg - JMI Laboratories
Mariana Castanheira - JMI Laboratories
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.64(4), e00099-20
DOI: 10.1128/AAC.00099-20
PMID: 32015043
PMCID: PMC7179261
NLM abbreviation: Antimicrob Agents Chemother
ISSN: 0066-4804
eISSN: 1098-6596
Grant note: DOI: 10.13039/100010643, name: Cidara Therapeutics
Language: English
Date published: 03/24/2020
Academic Unit: Epidemiology; Pathology
Record Identifier: 9984185173102771

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