Annual Report on the External Quality Assessment Scheme for Clinical Parasitology in Korea (2017)

Annual proficiency surveys were conducted in March, May, and August of 2017 as the Korean Association of External Quality Assessment Service. Overall, four image samples (MPI-17-01, MPI-17-02, MPI-17-03, MPI-17-04) in the first trial, three image samples (MPI-17-05, MPI-17-06 , MPI-17-07) in the second trial, and a slide specimen (MPS-17-01) using parasite samples in the third trial were distributed to participating institutions. The first and second trial specimens were prepared by photographing slides made of formalin-ether concentrate of positive samples stored for educational purposes. The slide distributed in the third trial was prepared using cellophane tape, which was stored after diagnosis of the patients infected with Enterobius vermicularis . There were 191 participating institutions in the first, 204 in the second, and 212 in the third trial. The correct identification rates were 27.2% for MPI-17-01 Diphyllobothrium species (sp.), 96.6% for MPI-17-02 no parasite, 67.5% for MPI-17-03 Metagonimus yokogawai , 71.2% for MPI-17-04 Balantidium coli , 99.0% for MPI-17-05 Taenia sp., 99.0% for MPI-17-06 Trichuris trichiura , 92.7% for MPI-17-07 Cryptosporidium sp., and 96.7% for MPS-17-01 E. vermicularis . The current external quality assessment for clinical parasitology was performed using image samples and standard slides. Surveys of parasitic infections should be accompanied by continuous education on various parasitic infections, for which there was lack of experience of inspection in clinical laboratories. In the future, it will be necessary to establish a standard material using parasitic samples, and ultimately to conduct a survey on whole series of tests for the diagnosis of parasitic diseases.

Internal Quality Assurance Status of Stool Examination as Assessed by a Questionnaire in Korean Clinical Laboratories

This study aimed to survey the status of quality control (QC) assurance for stool examinations at clinical laboratories in Korea. We sent a questionnaire related to QC practices in stool examination by electronic mail to Korean clinical laboratories that performed stool examination. Overall, 20 of the 39 laboratories (51.3%) reported performing stool concentration methods, and 28 (71.8%) examined the slides using only saline. A large proportion (74.4%) of respondents did not check the internal QC because of the restriction of appropriate control materials. Only four laboratories (10.3%) checked the reactivity of the dye solution routinely. For appropriate external QC systems, QC slides (43.6%) were preferred, followed by QC materials (30.8%), virtual slides (17.9%), and a combination of the above options (7.7%). The most commonly observed parasites in stool samples at the clinical laboratories were Clonorchis sinensis (75%), followed by Endolimax nana, Enterobius vermicularis, and Entamoeba coli. The present study describes the difficulties in internal QC assessment due to the absence of standardized QC materials and systems. We hope the findings of this report will provide a foundation for a QC assessment program for stool examinations in the near future.

Detection of Intestinal Parasites in Diarrhea Samples Using Various Diagnostic Methods and Evaluation of the Stability of In-house Quality Control Materials for Stool Examination

BACKGROUND: Because of a lack of quality control (QC) materials, stool examination has not been standardised. This study examined intestinal parasites in diarrhea specimens to manufacture and evaluate the performance stability of QC materials for stool examination. METHODS: This study examined diarrhea specimens submitted for stool culture. Microscopic examination was performed using the direct smear and formalin-ether concentration method (Military General Laboratory, MGL). Enzyme-linked immunosorbent assay (ELISA) kits (R-Biopharm AG, Germany) and xTAG Gastrointestinal Pathogen Panel (Luminex Corp., USA) were used for the three major protozoa: Cryptosporidium parvum, Giardia lamblia, and Entamoeba histolytica. Polymerase chain reaction (PCR) was performed for Dientamoeba fragilis and Blastocystis hominis. The QC materials for stool examination were generated using Diphyllobothrium nihonkaiense ova. The manufactured QC materials were evaluated under different storage conditions, with varying preservatives, temperatures, and storage times. RESULTS: From November 2015 to April 2016, 82 diarrhea specimens were collected and tested. All results from microscopy and ELISA were negative; C. parvum (n=2) and G. lamblia (n=1) were detected by xTAG, while D. fragilis (n=10) and B. hominis (n=2) were detected by PCR. High- and low-concentration QC materials were manufactured. Using the high-concentration QC material, ova were observed in all storage conditions using MGL. Using the low-concentration QC material, the ova were observed until 14 days, but not after 3 weeks. CONCLUSIONS: It should be considered for making QC materials for stool examinations that focus on D. fragilis and B. hominis frequently found in Korea and with the caution to the low-concentration of QC materials could be unstable.

Comparison of the Bruker Biotyper and VITEK MS Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Systems Using a Formic Acid Extraction Method to Identify Common and Uncommon Yeast Isolates

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows rapid and accurate identification of clinical yeast isolates. In-tube formic acid/acetonitrile (FA/ACN) extraction is recommended prior to the analysis with MALDI Biotyper, but the direct on-plate FA extraction is simpler. We compared the Biotyper with the VITEK MS for the identification of various clinically relevant yeast species, focusing on the use of the FA extraction method. METHODS: We analyzed 309 clinical isolates of 42 yeast species (four common Candida species, Cryptococcus neoformans, and 37 uncommon yeast species) using the Biotyper and VITEK MS systems. FA extraction was used initially for all isolates. If ‘no identification' result was obtained following the initial FA extraction, these samples were then retested by using FA (both systems, additive FA) or FA/ACN (Biotyper only, additive FA/ACN) extraction. These results were compared with those obtained by sequence-based identification. RESULTS: Both systems correctly identified all 158 isolates of the four common Candida species after the initial FA extraction. The Biotyper correctly identified 8.7%, 30.4%, and 100% of 23 C. neoformans isolates after performing initial FA, additive FA, and FA/ACN extractions, respectively, while VITEK MS identified all C. neoformans isolates after the initial FA extraction. Both systems had comparable identification rates of 37 uncommon yeast species (128 isolates), following the initial FA (Biotyper, 74.2%; VITEK MS, 73.4%) or additive FA (Biotyper, 82.0%; VITEK MS, 73.4%). CONCLUSIONS: The identification rate of most common and uncommon yeast isolates is comparable between simple FA extraction/Biotyper method and VITEK MS methods, but FA/ACN extraction is necessary for C. neoformans identification by Biotyper.

Increasing Burden of Nontuberculous Mycobacteria in Korea

No abstract available.

First Case Report of Bacteremia Due to Catabacter hongkongensis in a Korean Patient

No abstract available.

Performance Evaluation of Automated Clinical Chemistry Analyzer for Indocyanine Green (ICG) R15 Test

BACKGROUND: The conventional indocyanine green retention rate at 15 minutes (ICG R15) test is inefficient and inconvenient because it requires the use of a manual spectrophotometer and several samples per patient. This study aimed to establish the automation of the ICG R15 test using an automated clinical chemistry analyzer, and to evaluate the calculation of R15 with a small number of samples. METHODS: The performance of the AU5832 (Beckman Coulter, USA) for determining ICG concentration was evaluated in accordance with the Clinical Laboratory Standards Institute (CLSI) guidelines. The R15 results for 77 patients determined by spectrophotometry and AU5832 were compared. We evaluated the calculation of R15 with three samples, except for one sample in which the results had been obtained previously, at 5, 10, and 15 minutes after injection of ICG into the patients, and compared the results with those obtained with four samples. RESULTS: The automated ICG test using the AU5832 system showed proper performances according to CLSI. Although the difference in the R15 results between the two methods was within the 95% confidence interval, the R15 was adjusted by the regression equation because it was slightly lower according to the automated method compared with the manual method. The R15 with three samples (0, 5, and 15 minutes) showed the best correlation with conventional R15 with four samples (r2=0.996). Compared with the manual method, the R15 result using the AU5832 showed excellent agreement with four samples (kappa value 0.904) and with three samples (kappa value 0.880). CONCLUSIONS: The ICG R15 test using the AU5832 system is comparable with the conventional method in clinical use.

Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome

BACKGROUND: Little is known of the mutation and tumor spectrum of Korean patients with Li-Fraumeni syndrome (LFS). Owing to the rarity of LFS, few cases have been reported in Korea thus far. This study aimed to retrospectively review the mutations and clinical characteristics of Korean patients with LFS. METHODS: TP53 mutation was screened in 89 unrelated individuals at the Samsung Medical Center in Korea, from 2004 to 2015. Six additional mutation carriers were obtained from the literature. RESULTS: We identified nine different mutations in 14 Korean patients (male to female ratio=0.3:1). Two such frameshift mutations (p.Pro98Leufs*25, p.Pro27Leufs*17) were novel. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 (n=4; p.Arg273His and p.Arg273Cys). The median age at the first tumor onset was 25 yr. Ten patients (71%) developed multiple primary tumors. A diverse spectrum of tumors was observed, including breast (n=6), osteosarcoma (n=4), brain (n=4), leukemia (n=2), stomach (n=2), thyroid (n=2), lung (n=2), skin (n=2), bladder (n=1), nasal cavity cancer (n=1), and adrenocortical carcinoma (n=1). CONCLUSIONS: There was considerable heterogeneity in the TP53 mutations and tumor spectrum in Korean patients with LFS. Our results suggest shared and different LFS characteristics between Caucasian and Korean patients. This is the first report on the mutation spectrum and clinical characteristics from the largest series of Korean LFS patients.

Seroepidemiology of Toxocariasis and Its Clinical Implications in Gwangju and Jeonnam-province, Korea

We investigated the seroepidemiological, clinical, and laboratory characteristics of patients suspected to have toxocariasis in Gwangju and Jeonnam-province, Korea. In total, 228 specimens were analyzed for anti-Toxocara canis IgG at two university hospitals from 2010 to 2012. The overall seropositive rate was 67.1%, and the seropositive rates among the eosinophilic and non-eosinophilic groups were 76.1% (105/138) and 53.3% (48/90), respectively. Risk factors for eosinophilia and toxocariasis were male sex (odds ratios [OR]=2.632 and 3.477, respectively) and a history of ingesting raw meat (OR=2.884 and 3.274, respectively), especially raw cow liver (OR=2.089 and 10.038, respectively). T. canis seropositivity (OR=5.807, P=0.004) and a history of consuming raw cow liver (OR=2.766, P=0.052) were risk factors for organ involvement. The anti-T. canis IgG level showed weakly positive correlations with eosinophil counts (r=0.234, P<0.001) and the duration of eosinophilia (r=0.155, P=0.019). Although limited to the regions of Gwangju and Jeonnam-province, this study supports the opinion that toxocariasis is a reasonable focus as a cause of eosinophilia and that it is also associated with organ involvement.

Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry-Based VITEK MS System for the Identification of Acinetobacter Species from Blood Cultures: Comparison with VITEK 2 and MicroScan Systems

BACKGROUND: Acinetobacter species are the leading cause of bloodstream infection (BSI), but their correct identification is challenging. We evaluated the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS)-based VITEK MS (bioMerieux, France), and two automated systems, VITEK 2 (bioMerieux) and MicroScan (Siemens, USA) for identification of Acinetobacter BSI isolates. METHODS: A total of 187 BSI isolates recovered at a university hospital in Korea between 2010 and 2012 were analyzed. The identification results obtained using VITEK MS and two automated systems were compared with those of rpoB sequencing. RESULTS: Of 187 isolates analyzed, 176 were identified to the species level by rpoB sequencing: the Acinetobacter baumannii group (ABG; 101 A. baumannii, 43 A. nosocomialis, 10 A. pittii isolates) was most commonly identified (82.4%), followed by Acinetobacter genomic species 13BJ/14TU (5.3%), A. ursingii (2.1%), A. soli (2.1%), A. bereziniae (1.1%), and A. junii (1.1%). Correct identification rates to the species group (ABG) level or the species level was comparable among the three systems (VITEK MS, 90.3%; VITEK 2, 89.2%; MicroScan, 86.9%). However, VITEK MS generated fewer misidentifications (0.6%) than VITEK 2 (10.8%) and MicroScan (13.1%) (P<0.001). In addition, VITEK MS demonstrated higher specificity (100%) for discrimination between ABG and non-ABG isolates than the other systems (both, 31.8%) (P<0.001). CONCLUSIONS: The VITEK MS system is superior to the VITEK 2 and MicroScan systems for identification of Acinetobacter BSI isolates, with fewer misidentifications and better discrimination between the ABG and non-ABG isolates.

Cryptic e1a2 BCR-ABL1 Fusion With Complex Chromosomal Abnormality in de novo Myelodysplastic Syndrome

No abstract available.

Molecular Identification and Amphotericin B Susceptibility Testing of Clinical Isolates of Aspergillus From 11 Hospitals in Korea

BACKGROUND: We investigated the species distribution and amphotericin B (AMB) susceptibility of Korean clinical Aspergillus isolates by using two Etests and the CLSI broth microdilution method. METHODS: A total of 136 Aspergillus isolates obtained from 11 university hospitals were identified by sequencing the internal transcribed spacer (ITS) and beta-tubulin genomic regions. Minimal inhibitory concentrations (MICs) of AMB were determined in Etests using Mueller-Hinton agar (Etest-MH) and RPMI agar (Etest-RPG), and categorical agreement with the CLSI method was assessed by using epidemiological cutoff values. RESULTS: ITS sequencing identified the following six Aspergillus species complexes: Aspergillus fumigatus (42.6% of the isolates), A. niger (23.5%), A. flavus (17.6%), A. terreus (11.0%), A. versicolor (4.4%), and A. ustus (0.7%). Cryptic species identifiable by beta-tubulin sequencing accounted for 25.7% (35/136) of the isolates. Of all 136 isolates, 36 (26.5%) had AMB MICs of > or =2 microg/mL by the CLSI method. The categorical agreement of Etest-RPG with the CLSI method was 98% for the A. fumigatus, A. niger, and A. versicolor complexes, 87% for the A. terreus complex, and 37.5% for the A. flavus complex. That of Etest-MH was < or =75% for the A. niger, A. flavus, A. terreus, and A. versicolor complexes but was higher for the A. fumigatus complex (98.3%). CONCLUSIONS: Aspergillus species other than A. fumigatus constitute about 60% of clinical Aspergillus isolates, and reduced AMB susceptibility is common among clinical isolates of Aspergillus in Korea. Molecular identification and AMB susceptibility testing by Etest-RPG may be useful for characterizing Aspergillus isolates of clinical relevance.

Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

BACKGROUND: Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. METHODS: Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. RESULTS: Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. CONCLUSIONS: Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.

Constitutional Chromosomal Abnormality Identified in a Sibling Donor After Bone Marrow Stem Cell Transplantation in a Pediatric Patient with Acute Megakaryoblastic Leukemia

No abstract available.

Comparison of AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR for Detection of Mycobacterium tuberculosis Complex in Routine Clinical Practice

The AdvanSure tuberculosis/non-tuberculous mycobacterium (TB/NTM) PCR (LG Life Science, Korea) and COBAS TaqMan Mycobacterium tuberculosis (MTB) PCR (Roche Diagnostics, USA) are commonly used in clinical microbiology laboratories. We aimed to evaluate these two commercial real-time PCR assays for detection of MTB in a large set of clinical samples over a two-year period. AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR were performed on 9,119 (75.2%) and 3,010 (24.8%) of 12,129 (9,728 respiratory and 2,401 non-respiratory) MTB specimens, with 361 (4.0%) and 102 (3.4%) acid-fast bacilli (AFB)-positive results, respectively. In MTB culture, 788 (6.5%) MTB and 514 (4.2%) NTM were identified. The total sensitivity and specificity of the AdvanSure assay were 67.8% (95% confidence interval [CI], 63.9-71.6) and 98.3% (95% CI, 98.0-98.6), while those of the COBAS TaqMan assay were 67.2% (95% CI, 60.0-73.8) and 98.4% (95% CI, 97.9-98.9), respectively. The sensitivities and specificities of the AdvanSure and COBAS TaqMan assays for AFB-positive and AFB-negative samples were comparable. Furthermore, the AdvanSure assay showed fewer invalid results compared with the COBAS TaqMan assay (5.0 vs. 20.4 invalid results/1,000 tests, P<0.001). AdvanSure assay represents a comparable yet more reliable method than COBAS TaqMan for the identification of mycobacteria in routine clinical microbiology.

Presymptomatic Identification of CDH1 Germline Mutation in a Healthy Korean Individual with Family History of Gastric Cancer

Gastric cancer (GC) is one of the most common cancers with high morbidity and mortality. Familial GC is seen in 10% of cases, and approximately 3% of familial GC cases arise owing to hereditary diffuse gastric cancer (HDGC). CDH1, which encodes the protein E-cadherin, is the only gene whose mutations are associated with HDGC. Screening for the familial GC-predisposing gene has been neglected in high-risk countries such as Korea, China, and Japan, where all the cases have been attributed to Helicobacter pylori or other carcinogens. Screening for the GC-causing CDH1 mutation may provide valuable information for genetic counseling, testing, and risk-reduction management for the as-yet unaffected family members. An asymptomatic 44-yr-old Korean male visited our genetic clinic for consultation owing to his family history of GC. Eventually, c.1018A>G in CDH1, a known disease-causing mutation, was found. As of the publication time, the individual is alive without the evidence of GC, and is on surveillance. To our knowledge, this is the first Korean case of presymptomatic detection of CDH1 mutation, and it highlights the importance of genetic screening for individuals with a family history of GC, especially in high-risk geographical areas.

Direct Measurement of Serum Immunoglobulin Heavy and Light Chain Pairs for Identification of Monoclonal Gammopathy and a Performance Comparison with Capillary Electrophoresis

BACKGROUND: Determination of monoclonal gammopathy through conventional protein electrophoresis is sometimes difficult because of the presence of large proteins such as haptoglobin and transferrin, which may obscure the results. Ambiguity in an electrophoresis band can give rise to confusion or difficulty in interpretation. The heavy chain/light chain assay (HLC assay) using Hevylite antibody (The Binding Site, UK) has recently been developed for the accurate measurement of monoclonal proteins. We compared the immunotyping (IT) profiles to the immunoglobulin (Ig) heavy/light chain measurements obtained using the HLC assay and observed the ratios between intact Ig kappa and lambda. METHODS: We collected 35 and 28 sera from patients with suspicious and definitive monoclonal protein, respectively. Then we performed serum protein electrophoresis (SPEP) and IT by Capillarys2 (Sebia, USA). Monoclonal protein production was investigated using Freelite antibody (The Binding Site) and specific Ig(G, A)kappa and Ig(G, A)lambda Hevylite antibodies. The results were analyzed using PASW 18.0 for Windows (IBM, USA). RESULTS: Direct measurement of Ig heavy/light chains showed discordant IT results for 12 (34.2%) of 35 patients' sera with suspicious SPEP pattern and identical IT results for 28 patients' sera with definitive monoclonal peak in the SPEP results. Overall, the results of the HLC assay and IT showed good agreement (kappa=0.718, P=0.000 by cross-tabulation Gamma, Kappa analysis). CONCLUSIONS: The results of direct measurement of serum Ig heavy chain/light chain pairs were comparable to those of IT and were helpful for determination of monoclonality in the case of ambiguous electrophoresis results. Measurement of the heavy chain/light chain pair ratio also allowed precise quantification of the monoclonal Igs with ambiguous electrophoresis patterns and identification or discrimination of clonality.

Comparison between V-Tubes and BD Vacutainer Tubes for Use in Laboratory Tests

BACKGROUND: Vacuum tubes are widely used in clinical laboratories for routine tests. We compared a newly developed V-tube (AB Medical, Korea) and BD tubes (BD, USA) in common clinical assays, i.e., hematological, chemical, and immunological tests. METHODS: In total, 100 volunteers comprising 79 patients and 21 healthy volunteers were recruited and peripheral blood samples were collected with 2 brands of EDTA tubes and serum-separating tubes (SSTs). EDTA-tube samples were evaluated using 16 routine hematological tests. The SST samples were analyzed for 32 routine chemical parameters and 3 thyroid hormones. The results were statistically analyzed using the paired t-test and Bland-Altman plot. In addition, the stability of each analyte in 2 brands of vacutainers was evaluated. The results of the hematological tests at t=0 hr were compared with those at t=72+/-2 hr, and the results of the chemical parameters and thyroid hormones at t=0 hr were compared with those at t=72+/-2 hr and t=168+/-2 hr for each tube. RESULTS: Paired t-test analysis revealed that the test results of 16 routine hematological parameters, 32 routine chemical parameters, and 3 thyroid hormones showed clinically allowable differences between the 2 brands of vacuum tubes (t=0 hr). The results obtained when using V-tubes showed a statistically significant correlation with those obtained when using BD tubes. The stability of each analyte was similar in both vacuum tubes. Except for 10 parameters (white blood cell count, mean corpuscular volume, basophils [%], mean corpuscular hemoglobin concentration, monocytes [%], phospholipid, sodium, potassium, chloride, and free T4), all parameters showed significant but clinically allowable differences with regard to storage duration. CONCLUSIONS: The newly developed V-tube vacutainers provide a suitable alternative to BD tubes in common clinical laboratories.

In Vitro Fluconazole and Voriconazole Susceptibilities of Candida Bloodstream Isolates in Korea: Use of the CLSI and EUCAST Epidemiological Cutoff Values

BACKGROUND: At present, the clinical breakpoints (CBPs) of both fluconazole and voriconazole are available only for 3 common Candida species in the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methods. Epidemiological cutoff values (ECVs) were recently applied to both methods to detect the emergence of acquired resistance (i.e., non-wild-type isolates) among 5 common Candida species. METHODS: We performed a nationwide study to determine the fluconazole and voriconazole susceptibility of Candida bloodstream isolates (BSIs) using both the CLSI and EUCAST methods. A total of 423 BSIs of 5 Candida species were collected from 8 hospitals. The azole susceptibilities were assessed on the basis of the species-specific CBPs and ECVs. RESULTS: Of the 341 BSIs of 3 common Candida species (i.e., C. albicans, C. tropicalis, and C. parapsilosis), 0.3% and 0.9%, 0.0% and 1.5% of isolates were categorized as fluconazole and voriconazole resistant according to the CLSI and EUCAST CBPs, respectively. Of 423 total BSIs, 1.4% and 2.6% had fluconazole minimum inhibitory concentrations (MICs) exceeding the ECVs according to the CLSI and EUCAST, respectively; 1.0% and 2.1% had voriconazole MICs exceeding the ECVs according to the CLSI and EUCAST, respectively. Categorical agreement between the methods using ECVs was 98.3% for fluconazole and 98.3% for voriconazole. CONCLUSIONS: The EUCAST and CLSI methods using ECVs provide highly concordant results. Moreover, non-wild-type isolates with possibly acquired azole resistance were rare among the BSIs of 5 common Candida species in Korea.

In Vitro Fluconazole and Voriconazole Susceptibilities of Candida Bloodstream Isolates in Korea: Use of the CLSI and EUCAST Epidemiological Cutoff Values

BACKGROUND: At present, the clinical breakpoints (CBPs) of both fluconazole and voriconazole are available only for 3 common Candida species in the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) methods. Epidemiological cutoff values (ECVs) were recently applied to both methods to detect the emergence of acquired resistance (i.e., non-wild-type isolates) among 5 common Candida species. METHODS: We performed a nationwide study to determine the fluconazole and voriconazole susceptibility of Candida bloodstream isolates (BSIs) using both the CLSI and EUCAST methods. A total of 423 BSIs of 5 Candida species were collected from 8 hospitals. The azole susceptibilities were assessed on the basis of the species-specific CBPs and ECVs. RESULTS: Of the 341 BSIs of 3 common Candida species (i.e., C. albicans, C. tropicalis, and C. parapsilosis), 0.3% and 0.9%, 0.0% and 1.5% of isolates were categorized as fluconazole and voriconazole resistant according to the CLSI and EUCAST CBPs, respectively. Of 423 total BSIs, 1.4% and 2.6% had fluconazole minimum inhibitory concentrations (MICs) exceeding the ECVs according to the CLSI and EUCAST, respectively; 1.0% and 2.1% had voriconazole MICs exceeding the ECVs according to the CLSI and EUCAST, respectively. Categorical agreement between the methods using ECVs was 98.3% for fluconazole and 98.3% for voriconazole. CONCLUSIONS: The EUCAST and CLSI methods using ECVs provide highly concordant results. Moreover, non-wild-type isolates with possibly acquired azole resistance were rare among the BSIs of 5 common Candida species in Korea.