Antifungal susceptibilities of bloodstream isolates of Candida species from nine hospitals in Korea: application of new antifungal breakpoints and relationship to antifungal usage.

Eun Jeong Won,Yeon-Joon Park,Young Uh,Shine-Young Kim,Dong Wook Ryang,Min Ji Choi,Jong Hee Shin,Mi-Kyung Lee,Soo Hyun Kim,Wee Gyo Lee,Myung Geun Shin,Soon Pal Suh,Vishnu Chaturvedi

doi:10.1371/journal.pone.0118770

Abstract

We applied the new clinical breakpoints (CBPs) of the Clinical and Laboratory Standards Institute (CLSI) to a multicenter study to determine the antifungal susceptibility of bloodstream infection (BSI) isolates of Candida species in Korea, and determined the relationship between the frequency of antifungal-resistant Candida BSI isolates and antifungal use at hospitals. Four hundred and fifty BSI isolates of Candida species were collected over a 1-year period in 2011 from nine hospitals. The susceptibilities of the isolates to four antifungal agents were determined using the CLSI M27 broth microdilution method. By applying the species-specific CBPs, non-susceptibility to fluconazole was found in 16.4% (70/428) of isolates, comprising 2.6% resistant and 13.8% susceptible-dose dependent isolates. However, non-susceptibility to voriconazole, caspofungin, or micafungin was found in 0% (0/370), 0% (0/437), or 0.5% (2/437) of the Candida BSI isolates, respectively. Of the 450 isolates, 72 (16.0%) showed decreased susceptibility to fluconazole [minimum inhibitory concentration (MIC) ≥4 μg/ml]. The total usage of systemic antifungals varied considerably among the hospitals, ranging from 190.0 to 7.7 defined daily dose per 1,000 patient days, and fluconazole was the most commonly prescribed agent (46.3%). By Spearman’s correlation analysis, fluconazole usage did not show a significant correlation with the percentage of fluconazole resistant isolates at hospitals. However, fluconazole usage was significantly correlated with the percentage of fluconazole non-susceptible isolates (r = 0.733; P = 0.025) or the percentage of isolates with decreased susceptibility to fluconazole (MIC ≥4 μg/ml) (r = 0.700; P = 0.036) at hospitals. Our work represents the first South Korean multicenter study demonstrating an association between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI.

Highlights

The incidence of Candida bloodstream infections (BSIs) has increased over the past several decades, and antifungal use has increased drastically worldwide [1, 2]
Several studies have evaluated the relationship between antifungal drug use and changes in the epidemiology of candidemia [4,5,6]; to date, few multicenter surveillance studies have been conducted on the relationship between antifungal drug use and the frequency of antifungal resistance of Candida BSI isolates at hospitals
Revised Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs) for fluconazole were applied to four common Candida isolates (C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata), and all C. krusei isolates are considered resistant to fluconazole irrespective of the minimum inhibitory concentration (MIC) [8]

Summary

Introduction

The incidence of Candida bloodstream infections (BSIs) has increased over the past several decades, and antifungal use has increased drastically worldwide [1, 2]. Antifungal Usage and Incidence of Candidemia between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI. We applied new species-specific CLSI CBPs in a multicenter study to determine the antifungal susceptibility of BSI isolates of Candida species in Korea, and investigated the relationship between the frequency of antifungal resistance of Candida BSI isolates and antifungal use at nine hospitals.

Results

Conclusion