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

J Antimicrob Chemother 2019 Oct;74(10):2943-2949

Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

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.


Download full-text PDF

Source
https://academic.oup.com/jac/article/74/10/2943/5536332
Publisher Site
http://dx.doi.org/10.1093/jac/dkz280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753477PMC
October 2019
59 Reads
5.313 Impact Factor

Publication Analysis

Top Keywords

triazole pc945
8
candida auris
8
isolates mics
4
mics azole
4
japanese south
4
korean isolates
4
azole endpoint
4
south korean
4
endpoint pc945
4
m27 third
4
third edition
4
clsi m27
4
determined clsi
4
pc945 triazoles
4
triazoles determined
4
collection japanese
4
culture collection
4
tertiary care
4
care hospital
4
isolates tertiary
4

References

(Supplied by CrossRef)
Candida auris candidaemia in Indian ICUs: analysis of risk factors
Rudramurthy et al.
J Antimicrob Chemother 2017
Multidrug-resistant endemic clonal strain of Candida auris in India
Chowdhary et al.
Eur J Clin Microbiol Infect Dis 2014

Similar Publications