Publications by authors named "Kyeong Seob Shin"

53 Publications

Dynamics and Predictors of Mortality Due to Candidemia Caused by Different Species: Comparison of Intensive Care Unit-Associated Candidemia (ICUAC) and Non-ICUAC.

J Fungi (Basel) 2021 Jul 24;7(8). Epub 2021 Jul 24.

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju 61469, Korea.

We investigated mortality and predictors of mortality due to intensive care unit-associated candidemia (ICUAC) versus non-ICUAC by species. This study included all candidemia cases in 11 hospitals from 2017 to 2018 in South Korea. The all-cause mortality rates in all 370 patients with ICUAC were approximately twofold higher than those in all 437 patients with non-ICUAC at 7 days (2.3-fold, 31.1%/13.3%), 30 days (1.9-fold, 49.5%/25.4%), and 90 days (1.9-fold, 57.8%/30.9%). Significant species-specific associations with 7- and 30-day ICUAC-associated mortality were not observed. Multivariate analysis revealed that ICU admission was an independent predictor of (OR, 2.07-2.48) and -associated mortality (OR, 6.06-11.54). Fluconazole resistance was a predictor of -associated mortality (OR, 2.80-5.14). Lack (less than 3 days) of antifungal therapy was the strongest predictor of 7-day mortality due to ICUAC caused by (OR, 18.33), (OR, 10.52), and (OR, 21.30) compared with 30- and 90-day mortality (OR, 2.72-6.90). ICUAC had a stronger association with lack of antifungal therapy (55.2%) than ICUAC caused by other species (30.6-36.7%, all < 0.05). Most predictors of mortality associated with ICUAC were distinct from those associated with non-ICUAC and were mediated by species.
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http://dx.doi.org/10.3390/jof7080597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397010PMC
July 2021

The Prognostic Ability of RAS Pathway-Related Gene Mutations in Patients with Myeloid Neoplasms Treated with Hypomethylating Agents.

Acta Haematol 2021 Jul 7:1-11. Epub 2021 Jul 7.

Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.

Introduction: This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs).

Methods: We performed next-generation sequencing on bone marrow aspiration samples of 59 patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome with excess blasts-2, or chronic myelomonocytic leukemia and treated with decitabine or azacitidine as a frontline therapy.

Results: A single gene with the most common mutations was TP53 (14 of 59 patients), and mutations in RAS pathway-related genes including KRAS, NRAS, FLT3, PTPN11, CBL, and KIT were found in 28.8% of patients. The overall response rate to HMAs was 33.9%. Predictive factors for a poor response were an age >75 years (p = 0.007), 3 or more gene mutations (p = 0.004), mutations in RAS pathway-related genes (p = 0.033), and a mutated NRAS gene (p = 0.042). An age >75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in NRAS (hazard ratio 4.440) were identified as poor prognostic factors for survival.

Conclusion: In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated NRAS was associated with inferior survival rates.
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http://dx.doi.org/10.1159/000516793DOI Listing
July 2021

A rapid quantitative on-site coronavirus disease 19 serological test.

Biosens Bioelectron 2021 Nov 5;191:113406. Epub 2021 Jun 5.

BioNano Health Guard Research Center, Daejeon, 34141, Republic of Korea; BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 34141, Republic of Korea. Electronic address:

On-site severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) serological assays allow for timely in-field decisions to be made regarding patient status, also enabling population-wide screening to assist in controlling the coronavirus disease 2019 (COVID-19) pandemic. Here we propose a rapid microfluidic serological assay with two unique functions of nanointerstice filling and digitized flow control, which enable the fast/robust filling of the sample fluid as well as precise regulation of duration and volume of immune reaction. Developed microfluidic assay showed enhanced limit of detection, and 91.67% sensitivity and 100% specificity (n = 152) for clinical samples of SARS CoV-2 patients. The assay enables daily monitoring of IgM/IgG titers and patterns, which could be crucial parameters for convalescence from COVID-19 and provide important insight into how the immune system responds to SARS CoV-2. The developed on-site microfluidic assay presented the mean time for IgM and IgG seroconversions, indicating that these titers plateaued days after seroconversion. The mean duration from day 0 to PCR negativity was 19.4 days (median 20 d, IQR 16-21 d), with higher IgM/IgG titres being observed when PCR positive turns into negative. Simple monitoring of these titres promotes rapid on-site detection and comprehensive understanding of the immune response of COVID-19 patients.
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http://dx.doi.org/10.1016/j.bios.2021.113406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178056PMC
November 2021

Serological Evidence of and SARS-CoV-2 Co-infection: A Case Report.

Ann Lab Med 2021 09;41(5):510-513

Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

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http://dx.doi.org/10.3343/alm.2021.41.5.510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041590PMC
September 2021

Risk Factors for Extended-Spectrum-β-Lactamase-Producing in Community-Onset Bloodstream Infection: Impact on Long-Term Care Hospitals in Korea.

Ann Lab Med 2021 Sep;41(5):455-462

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: The prevalence of extended-spectrum β-lactamase-producing (ESBL-EC) in the community has increased worldwide due to multifactorial reasons. ESBL-EC bloodstream infection (BSI) complicates the decision for proper antimicrobial administration. In this multicenter study, we investigated the prevalence, risk factors, and molecular background of community-onset (CO) ESBL-EC BSI.

Methods: We included data for all episodes of ESBL-EC BSI of community origin from May 2016 to April 2017 obtained from the Korean national antimicrobial resistance surveillance system, which comprises six sentinel hospitals. Data, including previous history of admission and use of antimicrobials and medical devices before BSI, were collected, along with microbiological analysis results.

Results: Among 1,189 patients with CO BSI caused by , 316 (27%) were identified as ESBL producers. History of admission, especially to a long-term care hospital (LTCH), and previous use of β-lactams/β-lactamase inhibitors, carbapenem, lincosamide, aminoglycoside, and extended-spectrum cephalosporin were independent risk factors for CO ESBL-EC BSI; admission to an LTCH showed the highest odds ratio (3.8, 95% confidence interval 2.3-6.1). The most common genotype was CTX-M-15 (N=131, 41%), followed by CTX-M-14 (N=86, 27%). ST131 was the most common sequence type among ESBL-EC groups (57%).

Conclusions: In Korea, 27% of CO BSI were caused by ESBL producers. From perspectives of empirical treatment and infection control, history of admission to an LTCH and antimicrobial use should be noted.
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http://dx.doi.org/10.3343/alm.2021.41.5.455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041596PMC
September 2021

Coagulopathy profiles and their correlation with molecular viral burden in patients with COVID-19.

Blood Res 2021 Mar;56(1):56-58

Department of Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.

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http://dx.doi.org/10.5045/br.2021.2020210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987471PMC
March 2021

Peptide Nucleic Acid (PNA)-Enhanced Specificity of a Dual-Target Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) Assay for the Detection and Differentiation of SARS-CoV-2 from Related Viruses.

Diagnostics (Basel) 2020 Sep 30;10(10). Epub 2020 Sep 30.

Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju 28644, Korea.

The threat posed by coronaviruses to human health has necessitated the development of a highly specific and sensitive viral detection method that could differentiate between the currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-related coronaviruses (SARSr-CoVs). In this study, we developed a peptide nucleic acid (PNA)-based real-time quantitative polymerase chain reaction (RT-qPCR) assay targeting the N gene to efficiently discriminate SARS-CoV-2 from other SARSr-CoVs in human clinical samples. Without compromising the sensitivity, this method significantly enhanced the specificity of SARS-CoV-2 detection by 100-fold as compared to conventional RT-qPCR. In addition, we designed an RT-qPCR method for the sensitive and universal detection of ORF3ab-E genes of SARSr-CoV with a limit of detection (LOD) of 3.3 RNA copies per microliter. Thus, the developed assay serves as a confirmative dual-target detection method. Our PNA-mediated dual-target RT-qPCR assay can detect clinical SARS-CoV-2 samples in the range of 18.10-35.19 Ct values with an 82.6-100% detection rate. Furthermore, our assay showed no cross-reactions with other coronaviruses such as human coronaviruses (229E, NL63, and OC43) and Middle East respiratory syndrome coronavirus, influenza viruses (Type B, H1N1, H3N2, HPAI H5Nx, and H7N9), and other respiratory disease-causing viruses (MPV, RSV A, RSV B, PIV, AdV, and HRV). We, thus, developed a PNA-based RT-qPCR assay that differentiates emerging pathogens such as SARS-CoV-2 from closely related viruses such as SARSr-CoV and allows diagnosis of infections related to already identified or new coronavirus strains.
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http://dx.doi.org/10.3390/diagnostics10100775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601008PMC
September 2020

Germline V617F mutation as a susceptibility gene causing myeloproliferative neoplasm in first-degree relatives.

Leuk Lymphoma 2020 12 7;61(13):3251-3254. Epub 2020 Aug 7.

Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.

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http://dx.doi.org/10.1080/10428194.2020.1802448DOI Listing
December 2020

Environmental surface testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during prolonged isolation of an asymptomatic carrier.

Infect Control Hosp Epidemiol 2020 Nov 16;41(11):1328-1330. Epub 2020 Jun 16.

Department of Pediatrics, Chungbuk National University Hospital, Cheongju, Korea.

Environmental surface testing was performed to search for evidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) environmental contamination by an asymptomatic SARS-CoV-2 carrier with persistently high viral loads under isolation. No evidence of environmental contamination was found. Further studies are needed to measure environmental contamination by SARS-CoV-2 carriers and to determine reasonable isolation periods.
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http://dx.doi.org/10.1017/ice.2020.300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324661PMC
November 2020

Human Granulocytic Anaplasmosis Diagnosed Based on a Peripheral Blood Smear Test in South Korea: a Case Report.

Jpn J Infect Dis 2020 Nov 29;73(6):469-472. Epub 2020 May 29.

Department of Internal Medicine, Chungbuk National University Hospital, Republic of Korea.

We report a case of human granulocytic anaplasmosis (HGA) in a 76-year-old woman, diagnosed rapidly based on the characteristic peripheral blood smear finding of intragranulocytic morulae. The smear was prepared on the day of hospitalization, which was 1-2 weeks before results of the serology test or polymerase chain reaction (PCR) became available. Owing to the blood smear test, we could start timely and appropriate antimicrobial treatment. The sensitivity of peripheral blood smear is lower compared to that of serology or PCR for the diagnosis of HGA but may increase with the examiner's experience. In our case, the diagnosis of HGA was confirmed based on PCR and serology 7 and 14 days after the positive peripheral blood smear test, respectively. Morulae in neutrophils are a diagnostic indicator of HGA, particularly for febrile patients with a history of tick bites or outdoor activities in rural areas.
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http://dx.doi.org/10.7883/yoken.JJID.2020.013DOI Listing
November 2020

Impact of -Positive Enterococcus faecium Exhibiting Diverse Susceptibility Phenotypes to Glycopeptides on 30-Day Mortality of Patients with a Bloodstream Infection.

Antimicrob Agents Chemother 2020 06 23;64(7). Epub 2020 Jun 23.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea

This study was performed to evaluate the impacts of positivity of exhibiting diverse susceptibility phenotypes to glycopeptides on clinical outcomes in patients with a bloodstream infection (BSI) through a prospective, multicenter, observational study. A total of 509 patients with BSI from eight sentinel hospitals in South Korea during a 2-year period were enrolled in this study. Risk factors of the hosts and causative isolates were assessed to determine associations with the 30-day mortality of BSI patients via multivariable logistic regression analyses. The gene was detected in 35.2% (179/509) of isolates; 131 isolates exhibited typical VanA phenotypes (group -VanA), while the remaining 48 isolates exhibited atypical phenotypes (group -atypical), which included VanD ( = 43) and vancomycin-variable phenotypes ( = 5). A multivariable logistic regression indicated that positivity of causative pathogens was independently associated with the increased 30-day mortality rate in the patients with BSI; however, there was no significant difference in survival rates between the patients of the -VanA and -atypical groups (log rank test, 0.904). A high 30-day mortality rate was observed in patients with -positive BSIs, and positivity of causative isolates was an independent risk factor for early mortality irrespective of the susceptibility phenotypes to glycopeptides; thus, intensified antimicrobial stewardship is needed to improve the clinical outcomes of patients with -positive BSI.
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http://dx.doi.org/10.1128/AAC.02180-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318022PMC
June 2020

Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2.

Emerg Microbes Infect 2020 Dec;9(1):998-1007

Department of Microbiology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea.

The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 10 RNA copies close to that of qRT-PCR Notably, the assay has exhibited a rapid detection span of 30 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.
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http://dx.doi.org/10.1080/22221751.2020.1756698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301696PMC
December 2020

Neutrophil-erythrocyte rosettes in direct antiglobulin test-negative autoimmune hemolytic anemia.

Blood Res 2019 Sep 25;54(3):164. Epub 2019 Sep 25.

Department of Laboratory Medicine, Chungbuk National University Hospital, Cheongju, Korea.

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http://dx.doi.org/10.5045/br.2019.54.3.164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779931PMC
September 2019

A nationwide study of molecular epidemiology and antimicrobial susceptibility of Clostridioides difficile in South Korea.

Anaerobe 2019 Dec 23;60:102106. Epub 2019 Oct 23.

Yonsei University Wonju College of Medicine, Wonju, South Korea.

The molecular epidemiology and antimicrobial resistance of Clostridioides difficile were studied in South Korea in 2017 as part of a National Surveillance System. From February to May 2017, all non-duplicate isolates of C. difficile were recovered from patients who were suspected to have C. difficile infection and collected from 6 referral hospitals representing the 6 regions in South Korea. We performed PCRs for the toxin gene, PCR ribotyping, multilocus sequence typing (MLST), antimicrobial susceptibility testing by agar dilution according to the recommendations of the CLSI and detection of antimicrobial resistance genes such as ermB, catD, tetM, vanZ and nimR by PCR. Of 331 C. difficile isolates, 257 (77.6%) were toxigenic and the prevalence of strains producing binary toxin (CDT) was 5.1% (13/257). A total of 52 different ribotype (RT) patterns were found. RT018 was the most common (25.1% of all isolates), and RT014/020, RT002 and RT012 were also common. RT010 was most common non-toxigenic strain. MLST analysis of randomly selected 72 C. difficile isolates identified 46 sequence types (STs), of which three were new and not in the PubMLST library. There was a good correlation between MLST and RT as following: ST1 (RT027), ST8 (RT002), ST11 (RT078), ST17 (RT018), ST35 (RT046), ST37 (RT017), ST42 (RT106), ST53 (RT103), ST81 (RT369), and ST99 (RT070). All toxigenic isolates were susceptible to metronidazole and vancomycin (MIC ≤ 2 mg/L). For rifaximin, 24% of toxigenic isolates were resistant. Of randomly selected 106 toxigenic isolates, resistance rates for ampicillin, cefotetan, clindamycin, imipenem, chloramphenicol, tetracycline, and moxifloxacin were 48%, 46%, 64%, 54%, 0%, 6% and 52% respectively and frequencies of various resistance genes were 62.3% for ermB, 0.9% catD and 10.4% tetM. RTs018, 002, 017 and 369 showed high MICs to various antimicrobial agents and multi-drug resistance was common also.
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http://dx.doi.org/10.1016/j.anaerobe.2019.102106DOI Listing
December 2019

Risk factors of community-onset extended-spectrum β-lactamase-producing Klebsiella pneumoniae bacteraemia in South Korea using national health insurance claims data.

Int J Antimicrob Agents 2019 Dec 11;54(6):723-727. Epub 2019 Sep 11.

Division of Infectious Diseases, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea. Electronic address:

Background: Although it is essential to know the particular causes of antibiotic-resistant infections in the community, there is lack of evidence regarding risk factors for community-onset extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-KP) bacteraemia in South Korea. As such, this study aimed to identify risk factors for community-onset ESBL-KP bacteraemia.

Methods: From May 2016 to April 2017, patients with community-onset KP bloodstream infection (BSI) (n = 408) from six sentinel hospitals participating in the Global Antimicrobial Surveillance System in South Korea were included in this study. Risk factors of ESBL-KP BSI were assessed. Polymerase chain reaction and sequencing to identify genes encoding ESBLs and multi-locus sequence typing were performed.

Results: Of the 408 patients with community-onset KP BSI, 70 (17%) had ESBL-KP BSI. Admission to a long-term-care hospital within the previous 3 months [odds ratio (OR) 5.7, 95% confidence interval (CI) 2.1-15.6; P = 0.001], previous use of trimethoprim/sulfamethoxazole (TMP/SMT; OR 11.5, 95% CI 2.7-48.6; P = 0.001) or extended-spectrum cephalosporin (OR 2.2, 95% CI 1.2-3.9; P = 0.01), and previous use of a urinary catheter (OR 2.3, 95% CI 1.1-4.5; P = 0.02) were independent risk factors for community-onset ESBL-KP BSI. ESBL-KP isolates most frequently carried the CTX-M-1 group ESBL (74%, n = 52). The most prevalent sequence type (ST) among the ESBL-KP isolates was ST48 (14%, n = 10). Among non-ESBL-KP isolates, ST23 was most prevalent (21%, n = 70).

Conclusion: Previous admission to a long-term-care hospital, use of a urinary catheter and use of TMP/SMT or extended-spectrum cephalosporin within the previous 3 months were identified as risk factors for community-onset ESBL-KP BSI. Strict antibiotic stewardship and infection control measures are needed for long-term-care hospitals.
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http://dx.doi.org/10.1016/j.ijantimicag.2019.09.005DOI Listing
December 2019

Toxic Shock Syndrome Toxin 1-Producing Methicillin-Resistant Staphylococcus aureus of Clonal Complex 5, the New York/Japan Epidemic Clone, Causing a High Early-Mortality Rate in Patients with Bloodstream Infections.

Antimicrob Agents Chemother 2019 11 22;63(11). Epub 2019 Oct 22.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea

This study was performed to evaluate the clinical impacts of putative risk factors in patients with bloodstream infections (BSIs) through a prospective, multicenter, observational study. All 567 patients with BSIs that occurred during a 1-year period in six general hospitals were included in this study. Host- and pathogen-related variables were investigated to determine risk factors for the early mortality of patients with BSIs. The all-cause mortality rate was 15.0% (85/567) during the 4-week follow-up period from the initial blood culture, and 76.5% (65/85) of the mortality cases occurred within the first 2 weeks. One-quarter (26.8%, 152/567) of the blood isolates carried the gene, and most (86.2%, 131/152) of them were identified to be clonal complex 5 type 2 methicillin-resistant (MRSA) strains harboring staphylococcal cassette chromosome type II, belonging to the New York/Japan epidemic clone. A multivariable logistic regression showed that the positivity of the causative isolates was associated with an increased 2-week mortality rate both in patients with BSIs (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 0.90 to 2.88) and in patients with MRSA BSIs (aOR, 2.61; 95% CI, 1.19 to 6.03). Two host-related factors, an increased Pitt bacteremia score and advanced age, as well as a pathogen-related factor, carriage of by causative MRSA isolates, were risk factors for 2-week mortality in patients with BSIs. Careful management of patients with BSIs caused by the New York/Japan epidemic clone is needed to improve clinical outcomes.
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http://dx.doi.org/10.1128/AAC.01362-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811399PMC
November 2019

Counter Clinical Prognoses of Patients With Bloodstream Infections Between Causative Clones ST191 and ST451 Belonging to the International Clonal Lineage II.

Front Public Health 2019 16;7:233. Epub 2019 Aug 16.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.

This study was conducted to evaluate the possible clinical and bacteriologic features associated with 30-day mortality from bloodstream infections (BSIs). We conducted a prospective, multicenter, observational study of 181 entire episodes of BSI from six general hospitals between May 2016 and April 2017 in South Korea. Cox proportional-hazards regression model was used to estimate risks of the primary endpoint, i.e., all-cause mortality within 30 days from the initial blood culture. Most (84.5%) of the blood isolates belonged to the international clonal lineage II (ICLII) and 89.5% of the isolates were either multidrug- or extensively-drug resistant. We identified three risk factors including the old age of patient {hazard ratio, 1.033; [95% Confidential Interval (CI), 1.010-1.056]}, the sequential organ failure assessment score [1.133 (1.041-1.233)], and causative sequence type (ST) 191 belonging to ICLII [1.918 (1.073-3.430)], and three protective factors including causative ST451 belonging to ICLII [0.228 (0.078-0.672)], platelet count [0.996 (0.993-0.999)], and definitive therapy within 72 h [0.255 (0.125-0.519)]. Differing 30-day mortality rate in the dominant ICLII was observed by ST, which was much high in ST191 and low in ST451 and it was likely associated with the molecular traits, rather than the drug resistance.
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http://dx.doi.org/10.3389/fpubh.2019.00233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707333PMC
August 2019

Rapid and simple colorimetric detection of multiple influenza viruses infecting humans using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform.

BMC Infect Dis 2019 Aug 1;19(1):676. Epub 2019 Aug 1.

Department of Microbiology, College of Medicine and Medical Research Institute, Chungbuk National University, Chungdae-ro 1, Seowon-Ku, Cheongju, 28644, Republic of Korea.

Background: In addition to seasonal influenza viruses recently circulating in humans, avian influenza viruses (AIVs) of H5N1, H5N6 and H7N9 subtypes have also emerged and demonstrated human infection abilities with high mortality rates. Although influenza viral infections are usually diagnosed using viral isolation and serological/molecular analyses, the cost, accessibility, and availability of these methods may limit their utility in various settings. The objective of this study was to develop and optimized a multiplex detection system for most influenza viruses currently infecting humans.

Methods: We developed and optimized a multiplex detection system for most influenza viruses currently infecting humans including two type B (both Victoria lineages and Yamagata lineages), H1N1, H3N2, H5N1, H5N6, and H7N9 using Reverse Transcriptional Loop-mediated Isothermal Amplification (RT-LAMP) technology coupled with a one-pot colorimetric visualization system to facilitate direct determination of results without additional steps. We also evaluated this multiplex RT-LAMP for clinical use using a total of 135 clinical and spiked samples (91 influenza viruses and 44 other human infectious viruses).

Results: We achieved rapid detection of seasonal influenza viruses (H1N1, H3N2, and Type B) and avian influenza viruses (H5N1, H5N6, H5N8 and H7N9) within an hour. The assay could detect influenza viruses with high sensitivity (i.e., from 100 to 0.1 viral genome copies), comparable to conventional RT-PCR-based approaches which would typically take several hours and require expensive equipment. This assay was capable of specifically detecting each influenza virus (Type B, H1N1, H3N2, H5N1, H5N6, H5N8 and H7N9) without cross-reactivity with other subtypes of AIVs or other human infectious viruses. Furthermore, 91 clinical and spiked samples confirmed by qRT-PCR were also detected by this multiplex RT-LAMP with 98.9% agreement. It was more sensitive than one-step RT-PCR approach (92.3%).

Conclusions: Results of this study suggest that our multiplex RT-LAMP assay may provide a rapid, sensitive, cost-effective, and reliable diagnostic method for identifying recent influenza viruses infecting humans, especially in locations without access to large platforms or sophisticated equipment.
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http://dx.doi.org/10.1186/s12879-019-4277-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669974PMC
August 2019

Antimicrobial resistance in South Korea: A report from the Korean global antimicrobial resistance surveillance system (Kor-GLASS) for 2017.

J Infect Chemother 2019 Nov 13;25(11):845-859. Epub 2019 Jul 13.

Department of Laboratory Medicine, Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

At the end of 2015, a global action plan on antimicrobial resistance (AMR) was proposed by the World Health Organization, and the Global AMR Surveillance System (GLASS) was subsequently initiated. The Centers for Disease Control and Prevention of South Korea established a customized AMR surveillance system for South Korea, called Kor-GLASS, in early 2016. A pilot phase of Kor-GLASS was operated from May to December 2016 with six sentinel hospitals, and phase I of Kor-GLASS started in January 2017 with eight sentinel hospitals. Previous surveillance data for overestimated AMR due to duplicate isolation of drug-resistant pathogens were corrected and error-free AMR data were compared with those from other countries. One-half (53.2%, 377/708) of Staphylococcus aureus blood strains exhibited resistance to cefoxitin, indicating methicillin-resistant S. aureus. Resistance to ampicillin in Enterococcus faecalis blood strains was rare (0.6%, 1/175), while the resistance rate to penicillin was 26.3% (46/175). Resistance to vancomycin (34.0%, 98/288) and teicoplanin (18.8%, 98/288) was frequently observed in Enterococcus faecium strains. The resistance rate of Escherichia coli strains to cefotaxime was 32.4% (574/1772), and that of Klebsiella pneumoniae strains was 26.1% (181/693). The resistance rates of Pseudomonas aeruginosa strains to imipenem and meropenem were 19.5% (29/149) and 18.1% (27/149), respectively. And 92.1% (187/203) of Acinetobacter baumannii strains were resistant to both imipenem and meropenem. The high incidence of bacteremia caused by major AMR pathogens among hospitalized patients especially in intensive care units emphasized the importance of hospital infection control and the need to improve the crowded hospitalization system in South Korea. The isolation rate of the Salmonella spp. is decreasing, reflecting the current socio-economic status of South Korea. The proportions of bacterial species in the blood strains were similar to those in other Asian countries with similar lifestyles.
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http://dx.doi.org/10.1016/j.jiac.2019.06.010DOI Listing
November 2019

Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Isolates in Korea between 2014 and 2016.

Ann Lab Med 2019 Nov;39(6):537-544

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

Background: Several factors contribute to differences in serotype distribution. We investigated the serotype distribution and antimicrobial resistance of isolated between 2014 and 2016 in Korea.

Methods: We collected a total of 1,855 isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern.

Results: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively.

Conclusions: There were significant changes in the major serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.
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http://dx.doi.org/10.3343/alm.2019.39.6.537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660335PMC
November 2019

Mortality dynamics of Pseudomonas aeruginosa bloodstream infections and the influence of defective OprD on mortality: prospective observational study.

J Antimicrob Chemother 2019 09;74(9):2774-2783

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.

Background: To assess the mortality dynamics of patients with Pseudomonas aeruginosa bloodstream infections (BSIs) and the influence of OprD deficiencies of the microorganism on early mortality.

Methods: A prospective multicentre observational study was conducted with 120 patients with P. aeruginosa BSIs occurring between May 2016 and April 2017 in six general hospitals in South Korea. PCR and sequencing were carried out to identify the alterations in oprD and the presence of virulence factors. Cox regression was used to estimate the risk factors for mortality at each timepoint and Kaplan-Meier survival analyses were performed to determine the mortality dynamics.

Results: During the 6 week follow-up, 10.8% (13/120) of the patients with P. aeruginosa BSIs died in 2 weeks, 14.2% (17/120) in 4 weeks and 20.0% (24/120) in 6 weeks, revealing a steep decrease in cumulative survival between the fourth and sixth weeks. ICU admission and SOFA score were risk factors for mortality in any weeks after BSI onset and causative OprD-defective P. aeruginosa had a risk tendency for mortality within 6 weeks. Among the 120 P. aeruginosa blood isolates, 14 were XDR, nine produced either IMP-6 or VIM-2 MBL, and 21 had OprD deficiency.

Conclusions: BSIs caused by OprD-defective P. aeruginosa resulted in a 2-fold higher 6 week mortality rate (33.3%) than that of BSIs caused by OprD-intact P. aeruginosa (17.2%), likely due to the decreased susceptibility to carbapenems and bacterial persistence in clinical settings.
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http://dx.doi.org/10.1093/jac/dkz245DOI Listing
September 2019

Prospective Observational Study of the Clinical Prognoses of Patients with Bloodstream Infections Caused by Ampicillin-Susceptible but Penicillin-Resistant Enterococcus faecalis.

Antimicrob Agents Chemother 2019 07 24;63(7). Epub 2019 Jun 24.

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea

The purpose of this study was to evaluate the clinical impacts of ampicillin-susceptible but penicillin-resistant (ASPR) phenotypes of on clinical outcomes in patients with bloodstream infection (BSI). A total of 295 patients with an BSI from six sentinel hospitals during a 2-year period (from May 2016 to April 2018) were enrolled in this study. Putative risk factors, including host-, treatment-, and pathogen-related variables, were assessed to determine the associations with the 30-day mortality rate of patients with an BSI. The proportion of ASPR isolates was 22.7% (67/295). ASPR isolates (adjusted odds ratio, 2.27; 95% confidence interval, 1.01 to 5.02) exhibited a significant association with an increased 30-day mortality rate, and a significant difference in survival was identified in a group of patients treated with ampicillin- and/or piperacillin-based regimens who were stratified according to the penicillin susceptibility of the causative pathogen (0.011 by a log rank test). ASPR BSIs resulted in a >2-fold-higher 30-day mortality rate (26.9%; 18/67) than for the BSIs caused by penicillin-susceptible strains (12.3%; 28/228). The differences in mortality rates of patients stratified by penicillin susceptibility were likely due to the treatment failures of ampicillin and/or piperacillin in patients with an ASPR BSI.
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http://dx.doi.org/10.1128/AAC.00291-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591605PMC
July 2019

Establishment of the South Korean national antimicrobial resistance surveillance system, Kor-GLASS, in 2016.

Euro Surveill 2018 10;23(42)

Division of Antimicrobial Resistance, National Research Institute of Health, Centers for Disease Control and Prevention, Cheongju, Korea.

Surveillance plays a pivotal role in overcoming antimicrobial resistance (AMR) in bacterial pathogens, and a variety of surveillance systems have been set up and employed in many countries. In 2015, the World Health Organization launched the Global Antimicrobial Resistance Surveillance System (GLASS) as a part of the global action plan to enhance national and global surveillance and research. The aims of GLASS are to foster development of national surveillance systems and to enable collection, analysis and sharing of standardised, comparable and validated data on AMR between different countries. The South Korean AMR surveillance system, Kor-GLASS, is compatible with the GLASS platform and was established in 2016 and based on the principles of representativeness, specialisation, harmonisation and localisation. In this report, we summarise principles and processes in order to share our experiences with other countries planning to establish a national AMR surveillance system. The pilot operation of Kor-GLASS allowed us to understand the national burden of specific infectious diseases and the status of bacterial AMR. Issues pertaining to high costs and labour-intensive operation were raised during the pilot, and improvements are being made.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.42.1700734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199867PMC
October 2018

Antimicrobial resistance of major clinical pathogens in South Korea, May 2016 to April 2017: first one-year report from Kor-GLASS.

Euro Surveill 2018 10;23(42)

National Institute of Health, Centers of Disease Control and Prevention, Cheongju, Republic of Korea.

The Korean government established an antimicrobial resistance (AMR) surveillance system, compatible with the Global AMR Surveillance System (GLASS): Kor-GLASS. We describe results from the first year of operation of the Kor-GLASS from May 2016 to April 2017, comprising all non-duplicated clinical isolates of major pathogens from blood urine faeces and urethral and cervical swabs from six sentinel hospitals. Antimicrobial susceptibility tests were carried out by disk diffusion, Etest, broth microdilution and agar dilution methods. Among 67,803 blood cultures, 3,523 target pathogens were recovered. The predominant bacterial species were (n = 1,536), (n = 597) and (n = 584). From 57,477 urine cultures, 6,394 and 1,097 were recovered. Bloodstream infections in inpatients per 10,000 patient-days (10TPD) were highest for cefotaxime-resistant with 2.1, followed by 1.6 for meticillin-resistant , 1.1 for imipenem-resistant , 0.8 for cefotaxime-resistant and 0.4 for vancomycin-resistant . Urinary tract infections in inpatients were 7.7 and 2.1 per 10TPD for cefotaxime-resistant and , respectively. Kor-GLASS generated well-curated surveillance data devoid of collection bias or isolate duplication. A bacterial bank and a database for the collections are under development.
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http://dx.doi.org/10.2807/1560-7917.ES.2018.23.42.1800047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199864PMC
October 2018

Cohort Study of Pulmonary Tuberculosis (COSMOTB) identifying drug-resistant mutations: protocol for a prospective observational study in Korea.

BMJ Open 2018 10 10;8(10):e021235. Epub 2018 Oct 10.

Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.

Introduction: Drug-resistant tuberculosis (TB) is a global concern. The proper diagnosis and management of drug-resistant TB are critical for improving treatment outcome. Molecular-based genotypic drug-susceptibility testing (DST) was developed to identify drug-resistant TB; however, discordant results from phenotypic and genotypic DST analyses have alarmed clinicians and raised concerns about the test's utility. Moreover, the characteristics of disputed mutations are not well studied and only based on retrospective study findings.

Methods And Analysis: We describe a 28-month prospective observational cohort study ongoing at two university-affiliated hospitals in South Korea. The cohort study will enrol and evaluate 600 adults with pulmonary TB. Relevant clinical and epidemiological data will be collected prospectively and participants will be evaluated at each hospital during anti-TB treatment to identify factors associated with TB treatment outcomes. Respiratory specimens will be collected at select visits. After generating a well-characterised cohort, patterns of drug resistance on both phenotypic and genotypic DSTs and associated mutations including the disputed mutation will be evaluated. We will also identify various clinical and socioeconomic factors that affect the causes of drug resistance and their clinical outcomes.

Ethics And Dissemination: The study protocol is approved by the Institutional Review Boards of Chungbuk National University Hospital and Chungnam National University Hospital. Study results will be disseminated through peer-reviewed journals and conference presentations.

Trial Registration Number: KCT0002594.
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http://dx.doi.org/10.1136/bmjopen-2017-021235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252767PMC
October 2018

Antimicrobial resistance and virulence factors of Klebsiella pneumoniae affecting 30 day mortality in patients with bloodstream infection.

J Antimicrob Chemother 2019 01;74(1):190-199

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: To investigate the risk factors of patients with Klebsiella pneumoniae (KP) bloodstream infection (BSI) with a focus on antimicrobial resistance and virulence factors.

Methods: All KP BSI patients (n = 579) from six general hospitals during a 1 year period were included in this study. The risk factors of hosts and causative KP isolates were assessed to determine associations with the 30 day mortality of KP BSI patients by multivariate Cox hazards modelling.

Results: The 30 day mortality rate of KP BSI patients was 16.9% (98/579). Among the host-associated factors, increased SOFA score and leucopenia status exhibited strong associations with increased 30 day mortality. Among the pathogenic factors, carriage of the pks gene cluster (adjusted HR 1.80; 95% CI 1.16-2.79) was a risk factor, especially when accompanied by MDR. In this regard, KP isolates of the wzi50 capsular type (n = 22) frequently harboured pks (63.6%, 14/22) and ybtA (68.2%, n = 15) and mostly exhibited MDR (63.6%, n = 14), resulting in increased 30 day mortality. In contrast, hypermucoviscous KP isolates showed an inverse association with 30 day mortality (adjusted HR 0.55; 95% CI 0.33-0.90).

Conclusions: Despite the reported virulence of hypermucoviscous KP strains, they were associated with good prognoses in KP BSI patients. Importantly, carriage of the pks gene cluster, which is responsible for the synthesis of colibactin, was a relevant marker of early mortality.
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http://dx.doi.org/10.1093/jac/dky397DOI Listing
January 2019

Impact of host-pathogen-treatment tripartite components on early mortality of patients with Escherichia coli bloodstream infection: Prospective observational study.

EBioMedicine 2018 Sep 20;35:76-86. Epub 2018 Aug 20.

Department of Laboratory Medicine, Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

Background: Risk factors affecting early morality of patients with Escherichia coli bloodstream infection (BSI) were investigated including the host-pathogen-treatment tripartite components.

Methods: Six general hospitals in South Korea participated in this multicentre prospective observational study from May 2016 to April 2017 and a total of 1492 laboratory-confirmed E. coli BSI cases were studied. Cox regression was used to estimate risks of the primary endpoint, i.e., all-cause mortality within 30 days from the initial blood culture. Six multivariate analysis models were constructed in accordance to the clinical importance and intra- and inter-component multicollinearity.

Findings: Among the 1492 E. coli BSI cases, 9.5% (n = 141) patients expired within 30 days. Six models of multivariate analysis indicated risk factors of critical illness, primary infection of peritoneum, and chronic liver disease including cirrhosis for host variables; of phylogenetic group B2, ST131-sublineage H30Rx, multidrug resistance, group 1 CTX-M extended-spectrum beta-lactamase production, and having either of fyuA, afa, and sfa/foc virulence genes for causative E. coli pathogen variables; and of delayed definitive therapy for antimicrobial treatment variables. In addition, as a protective factor, primary urinary tract infection was identified.

Interpretation: Despite decades' effort searching for the risk factors for E. coli BSI, systemic understanding covering the entire tripartite component is still lacking. This study detailed the organic impact of host-pathogen-treatment tripartite components for early mortality in patients with E. coli BSI.
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http://dx.doi.org/10.1016/j.ebiom.2018.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161478PMC
September 2018

Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus.

Antimicrob Agents Chemother 2018 09 27;62(9). Epub 2018 Aug 27.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea

A total of 281 nonduplicated blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant (MRSA). Cefoxitin-disk diffusion tests and the gene PCR revealed that 56.6% (159/281) of the isolates were MRSA, and most belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159) were nonsusceptible to ceftaroline (MIC ≥ 2 mg/liter), whereas all of the methicillin-susceptible isolates were susceptible to the drug. Eight amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four (L357I, E447K, I563T, and S649A) in the penicillin-binding domain (PBD) and four (N104K, V117I, N146K, and A228V) in the non-PBD (nPBD) of PBP2a, were associated with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted in the elevation of ceftaroline MICs: one substitution at 1 to 2 mg/liter, two or three substitutions at 2 to 4 mg/liter, and five substitutions at 4 or 16 mg/liter. Ceftaroline resistance in MRSA might be the result of clone-specific PBP2a polymorphism, along with substitutions both in PBD and nPBD, and the elevated ceftaroline MICs were associated with the substitution sites and accumulation of substitutions.
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http://dx.doi.org/10.1128/AAC.00485-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125543PMC
September 2018
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