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

Autor:	Rudramurthy SM; Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India., Colley T; Pulmocide Ltd, London, UK., Abdolrasouli A; Department of Medical Microbiology, North West London Pathology, Imperial College Healthcare NHS Trust, London, UK.; National Heart and Lung Institute, Imperial College School of Medicine, London, UK., Ashman J; Pulmocide Ltd, London, UK., Dhaliwal M; Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India., Kaur H; Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India., Armstrong-James D; National Heart and Lung Institute, Imperial College School of Medicine, London, UK.; Department of Microbiology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Trust, London, UK., Strong P; Pulmocide Ltd, London, UK., Rapeport G; Pulmocide Ltd, London, UK., Schelenz S; Department of Microbiology, Royal Brompton Hospital, Royal Brompton and Harefield NHS Trust, London, UK., Ito K; Pulmocide Ltd, London, UK., Chakrabarti A; Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Jazyk:	angličtina
Zdroj:	The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2019 Oct 01; Vol. 74 (10), pp. 2943-2949.
DOI:	10.1093/jac/dkz280
Abstrakt:	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. (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu