In vitro antifungal activity of a novel topical triazole PC945 against emerging yeast Candida auris
Open accessAbstract
Objectives: 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. Methods: 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)]. Results: 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 correlation could be established with the MIC of PC945. Tentative epidemiological cut-off values (ECOFFs) evaluated by CLSI’s ECOFF Finder (at 99%) with 24 h reading of MICs were 1, 4 and 1 mg/L for PC945, voriconazole and posaconazole, respectively. MIC values for quality control strains of all triazoles were in the normal ranges. Conclusions: PC945 was found to be a more potent inhibitor than posaconazole, voriconazole and fluconazole of C. auris isolates collected globally, warranting further laboratory and clinical evaluations.
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PC945 is the first topical, inhaled triazole, designed primarily for invasive pulmonary aspergillosis, with prolonged lung tissue retention without significant systemic absorption and activity against posaconazole- and pan-azole-resistant A. fumigatus and C. auris.
“PC945 is the first topical, inhaled triazole. Developed by Pulmocide, this drug is designed primarily for the treatment of IPA, boasting prolonged lung tissue retention without significant systemic absorption. Its antifungal spectrum is analogous to systemic triazoles but with significantly greater potency maintaining activity against posaconazole and pan-azole-resistant A. fumigatus, as well as C”
From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [82]
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- Authors
- Rudramurthy, S. M., Colley, T., Abdolrasouli, A., Ashman, J., Dhaliwal, M., Kaur, H., Armstrong-James, D., Strong, P., Rapeport, G., Schelenz, S., Ito, K., & Chakrabarti, A.
- Affiliations
- Post Graduate Institute of Medical Education and Research (IN)
- Pulmocide Ltd, London, UK
- Imperial College Healthcare NHS Trust (GB)
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- Corresponding author
- Ito, Kazuhiro
- ORCID
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-07-19
- Volume
- 74
- Issue
- 10
- Pages
- 2943-2949
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- PMC
- PMC6753477
- OpenAlex
- W2963538331
- Cited by
- 44
- References
- 29
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 6
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc)
- Funders
- Pulmocide Ltd
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Keywords
- Candida auris, triazole antifungals, topical antifungal agents, antifungal susceptibility, fluconazole resistance, voriconazole, posaconazole, cross-resistance, ERG11 mutations, epidemiological cut-off values, emerging fungal infections
- MeSH terms
- Candida parapsilosis, Antifungal Agents, Asia, Benzamides, Candida, Candidiasis, United Kingdom, Humans, Microbial Sensitivity Tests, Triazoles, United States, Tertiary Care Centers
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