Antifungal Susceptibilities of Bloodstream Isolates of Candida Species from Nine Hospitals in Korea: Application of New Antifungal Breakpoints and Relationship to Antifungal Usage

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.

Resistance Mechanisms and Clinical Features of Fluconazole-Nonsusceptible Candida tropicalis Isolates Compared with Fluconazole-Less-Susceptible Isolates

“…tropicalis fungemia caused by FNS and FLS strains is uncommon in Korea (16). Among 565 C. tropicalis BSI isolates from Korean surveillance cultures between 2003 and 2013, only 6 (1.1%) displayed fluconazole MIC values of Ն4 g/ml, and 10 (1.8%) displayed fluconazole MIC values of 1 to 2 g/ml by the 24-h CLSI method.…”

“…Twenty-one FNS and FLS isolates were recovered from eight Korean university hospitals during performance of nationwide surveillance in Korea (2003Korea ( to 2013 (16,17) and were obtained from blood (n ϭ 16), urine (n ϭ 3), ear pus (n ϭ 1), and nasal swab (n ϭ 1). All 14 control isolates were obtained from blood cultures.…”

Multicenter Identification and Antifungal Susceptibility Patterns of Candida Species Isolated from Clinical Samples

“…Such a trend was reported using FLU and ITR as prophylaxis or treatment in patients, leading to resistant species, and treatment with other azoles failed. Resistance rate to FLU varied in different studies and for C. glabrata it was reported as 95% (38/40), 6.2% (1/16) and 10.3% (6/58 with 52/58 susceptible dose dependent) (6,11,23). These rates for C. krusei were 95.2% (59/62) (6).…”

Drug Resistance in Bacteria, Fungi, Malaria, and Cancer

“…3 isolates (16.6 %) (Fothergill et al 2014;Al-mamari et al 2014;Zhang et al 2015;Won et al 2015;83 isolates (Al-mamari et al 2014); C. glabrata, 111 isolates (Fothergill et al 2014); to VRC in C. albicans, i.e., 82 isolates (Fothergill et al 2014); C. glabrata, 258 isolates (Fothergill et al 2014); and C. tropicalis, 94 isolates (Fothergill et al 2014) (refer Table 2). 8 isolates (8.6 %); C. tropicalis i.e.…”