In vitro antifungal activity of a novel topical triazole PC945 against emerging yeast Candida auris.

The Journal of Antimicrobial Chemotherapy
Shivaprakash M RudramurthyArunaloke Chakrabarti

Abstract

Management of Candida auris infection is difficult as this yeast exhibits resistance to different classes of antifungals, necessitating the development of new antifungals. The aim of this study was to investigate the susceptibility of C. auris to a novel antifungal triazole, PC945, optimized for topical delivery. A collection of 50 clinical isolates was obtained from a tertiary care hospital in North India. Nine isolates from the UK, 10 from a CDC panel (USA) and 3 from the CBS-KNAW culture collection (Japanese and South Korean isolates) were also obtained. MICs (azole endpoint) of PC945 and other triazoles were determined in accordance with CLSI M27 (third edition). Quality control strains were included [Candida parapsilosis (ATCC 22019) and Candida krusei (ATCC 6258)]. Seventy-four percent of isolates tested showed reduced susceptibility to fluconazole (≥64 mg/L). PC945 (geometric mean MIC = 0.058 mg/L) was 7.4-fold and 1.5-fold more potent than voriconazole and posaconazole, respectively (both P < 0.01). PC945 MIC values correlated with those of voriconazole or posaconazole, and only three isolates were found to be cross-resistant between PC945 and other azoles. ERG11 sequence analysis revealed several mutations, but no corr...Continue Reading

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Citations

Jun 3, 2020·Antimicrobial Agents and Chemotherapy·Laís Salomão AriasJason L Brown
Jul 6, 2020·Current Topics in Medicinal Chemistry·Christophe Tratrat
May 1, 2021·International Journal of Molecular Sciences·Lucia ČernákováCélia F Rodrigues
Jun 3, 2021·Current Fungal Infection Reports·Garret T Seiler, Luis Ostrosky-Zeichner

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Methods Mentioned

BETA
bronchoalveolar
lavage
PCR

Software Mentioned

GraphPad
ECOFF Finder
PRISM

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