Publications by authors named "Heungsup Sung"

178 Publications

Performance of Xpert MTB/RIF for the Diagnosis of Extrapulmonary Tuberculosis.

Clin Lab 2021 Feb;67(2)

Background: Mycobacterial burden is low in extrapulmonary specimens, making diagnosis and treatment difficult. Xpert MTB/RIF is a real-time PCR assay for the detection of Mycobacterium tuberculosis and rifampin resistance. This study evaluated the performance of the Xpert MTB/RIF assay in extrapulmonary specimens.

Methods: Acid-Fast Bacilli (AFB) smear, culture, and Xpert MTB/RIF were performed on extrapulmonary specimens. Mycobacterial culture was performed on BACTEC MGIT liquid for 6 weeks and 2% Ogawa medium for 8 weeks. Overall sensitivity and specificity of Xpert MTB/RIF was estimated using culture as a gold standard. Xpert MTB/RIF sensitivity and cycle-threshold (Ct) values according to AFB smear grade were evaluated. The sensitivity, specificity, and concordance of rifampin resistance compared to the phenotypic drug sensitivity test were evaluated.

Results: A total of 1,289 specimens were included in the study. The overall sensitivity and specificity of the Xpert MTB/RIF assay were 59.4% (41/69, 95% CI 46.9 - 70.9%) and 99.3% (1,212/1,220, 95% CI 98.7 - 99.7), respectively. Positive predictive value of Xpert MTB/RIF was 83.7% (41/49, 95% CI 69.8 - 92.2) and negative predictive value was 97.7% (1,212/1,240, 95% CI 96.7 - 98.5%). Xpert MTB/RIF assay sensitivity significantly increased with increases in AFB smear grade (p < 0.001). AFB smear grades and Xpert MTB/RIF Ct values were negatively correlated. Rifampin resistance results of Xpert MTB/RIF and culture showed a concordance rate of 97.2%.

Conclusions: The Xpert MTB/RIF assay could be used to replace the AFB smear for the diagnosis of extrapulmonary tuberculosis, and has high specificity for the detection of rifampin resistance.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200423DOI Listing
February 2021

Reappraisal of the prognostic value of Epstein-Barr virus status in monomorphic post-transplantation lymphoproliferative disorders-diffuse large B-cell lymphoma.

Sci Rep 2021 Feb 3;11(1):2880. Epub 2021 Feb 3.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

The role of the Epstein-Barr virus (EBV) status in the blood for predicting survival in post-transplantation lymphoproliferative disorders-diffuse large B-cell lymphoma (PTLD-DLBCL) is unknown. We evaluated the prognostic values of pre-treatment EBV-encoded small RNA (EBER) detected with in situ hybridization in tissues and EBV DNA in the whole blood (WB) and plasma in 58 patients with monomorphic PTLD-DLBCL after solid organ transplantation. There were no significant differences in the rates of overall response, complete response, and survival according to EBER EBV and WB EBV status. In contrast, patients with positive plasma EBV DNA had significantly lower rates of overall response (60.0% vs. 94.4%, P = 0.043) and complete response (40.0% vs. 88.9%, P = 0.019) as well as worse progression-free survival (PFS) (P = 0.035) and overall survival (OS) (P = 0.039) compared with patients with negative plasma EBV DNA. In multivariate analysis, plasma EBV DNA positivity was a significantly unfavorable prognostic factor for PFS [hazard ratio (HR) 4.92, 95% confidence interval (CI) 1.22-19.86, P = 0.025] and OS (HR 4.48, 95% CI 1.14-17.63, P = 0.032). Despite small number of 6 patients with plasma EBV positivity, plasma EBV DNA positivity might be more prognostic for survival than EBER or WB EBV DNA positivity in patients with monomorphic PTLD-DLBCL.
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http://dx.doi.org/10.1038/s41598-021-82534-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859229PMC
February 2021

Epidemiologic Linkage of COVID-19 Outbreaks at Two University-affiliated Hospitals in the Seoul Metropolitan Area in March 2020.

J Korean Med Sci 2021 Jan 25;36(4):e38. Epub 2021 Jan 25.

Department of Laboratory Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea.

Background: Coronavirus disease 2019 (COVID-19) outbreaks emerged at two university-affiliated hospitals in Seoul (hospital A) and Uijeongbu City (hospital S) in the metropolitan Seoul area in March 2020. The aim of this study was to investigate epidemiological links between the outbreaks using whole genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Fifteen patients were enrolled in the study, including four non-outbreak (A1-A4) and three outbreak cases (A5-A7) in hospital A and eight cases (S1-S8) in hospital S. Patients' hospital stays, COVID-19 symptoms, and transfer history were reviewed. RNA samples were submitted for WGS and genome-wide single nucleotide variants and phylogenetic relationships were analyzed.

Results: The index patient (A5) in hospital A was transferred from hospital S on 26 March. Patients A6 and A7 were the family caregiver and sister, respectively, of the patient who shared a room with A5 for 4 days. Prior to transfer, A5 was at the next bed to S8 in the emergency room on 25 March. Patient S6, a professional caregiver, took care of the patient in the room next to S8's room for 5 days until 22 March and then S5 for another 3 days. WGS revealed that SARS-CoV-2 in A2, A3, and A4 belong to clades V/B.2, S/A, and G/B.1, respectively, whereas that of A5-A7 and S1-S5 are of the V/B.2.1 clade and closely clustered. In particular, SARS-CoV-2 in patients A5 and S5 showed perfect identity.

Conclusion: WGS is a useful tool to understand epidemiology of SARS-CoV-2. It is the first study to elucidate the role of patient transfer and caregivers as links of nosocomial outbreaks of COVID-19 in multiple hospitals.
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http://dx.doi.org/10.3346/jkms.2021.36.e38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834897PMC
January 2021

Epidemiology and Clinical Characteristics of Bloodstream Infection in Patients Under Extracorporeal Membranous Oxygenation.

J Intensive Care Med 2020 Dec 30:885066620985538. Epub 2020 Dec 30.

Department of Infectious Diseases, 65526Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Bloodstream infection (BSI) is an important complication of extracorporeal membranous oxygenation (ECMO) and a major cause of mortality. This study evaluated the epidemiological and clinical characteristics of BSI that occur during ECMO application according to microbial etiology.

Methods: Adult patients who underwent ECMO from January 2009 to December 2016 were retrospectively analyzed for BSI episodes at a 2,700-bed, tertiary center. Epidemiological and clinical characteristics and outcomes of BSI were evaluated and were compared for etiologic groups (gram-positive cocci, gram-negative rods, and fungi groups). Risk factors for 14-day mortality were analyzed.

Results: A total of 1,100 patients underwent ECMO during the study period, and 65 BSI episodes occurred in 61 patients. The BSI incidence was 8.3 episodes/1,000 ECMO days, which significantly decreased over time ( = 0.03), primarily in gram-positive cocci BSI. Gram-positive cocci, gram-negative rods, and fungi accounted for 38%, 40%, and 22% of the 73 blood isolates, respectively. Baseline characteristics were comparable between groups. Catheter-related infection (CRI) and pneumonia were the most common sources of BSI; 52% of gram-positive cocci BSIs and 79% of fungi BSIs were caused by CRI, and 75% of gram-negative BSIs by pneumonia. Patients with gram-negative rods BSI died more frequently and earlier than those with other BSIs. Independent risk factors for 14-day mortality were older age and gram-negative rods BSI.

Conclusions: The decreased BSI incidence during ECMO was mainly because of the decrease of gram-positive cocci BSI. The high early mortality of gram-negative rods BSI makes prevention and adequate treatment necessary.
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http://dx.doi.org/10.1177/0885066620985538DOI Listing
December 2020

Severe Human Bocavirus-Associated Pneumonia in Adults at a Referral Hospital, Seoul, South Korea.

Emerg Infect Dis 2021 Jan;27(1):226-228

We report a case series of severe human bocavirus-associated pneumonia in adults in Seoul, South Korea. The virus accounted for 0.5% of all severe pneumonia cases. Structural lung disease and hematologic malignancy were common underlying diseases. Overall death rate was 54.5%. Higher death rates were associated with co-infection (83.3%) and immunocompromise (80.0%).
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http://dx.doi.org/10.3201/eid2701.202061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774574PMC
January 2021

In Vitro Activities and Inoculum Effects of Ceftazidime-Avibactam and Aztreonam-Avibactam against Carbapenem-Resistant Isolates from South Korea.

Antibiotics (Basel) 2020 Dec 15;9(12). Epub 2020 Dec 15.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Ceftazidime-avibactam (CAZ-AVI) and aztreonam-avibactam (AZT-AVI) are novel antibiotic combinations active against multidrug-resistant Gram-negative pathogens. This study aimed to evaluate their in vitro activities and inoculum effects in carbapenem-resistant (CRE), including carbapenemase-producing (CP)-CRE and non-CP-CRE. A total of 81 independent clinical isolates of carbapenem-resistant and were collected. CAZ-AVI and AZT-AVI minimal inhibitory concentrations (MICs) were evaluated by broth microdilution using standard and high inocula. The inoculum effect was defined as an ≥8-fold increase in MIC with high inoculum. Phenotypic determination of β-lactam resistance mechanism and PCR for carbapenemase genes were performed. Of the 81 CRE isolates, 35 (43%) were CP-CRE. Overall, 73% of the isolates were susceptible to CAZ-AVI, and 95% had low AZT-AVI MICs (≤8 µg/mL). The MICMICs of CAZ-AVI and AZT-AVI were 4/≥512 µg/mL and 0.5/4 µg/mL, respectively. CAZ-AVI was more active against non-CP-CRE than against CP-CRE (susceptibility 80% vs. 63%, = 0.08; MIC/MIC, 2/16 μg/mL vs. 4/≥512 μg/mL), whereas AZT-AVI was more active against CP-CRE (MIC/MIC, 0.25/1 μg/mL vs. 0.5/8 μg/mL). All four isolates with high AZT-AVI MIC (≥16 μg/mL) were resistant to CAZ-AVI, but only 18% (4/22) of CAZ-AVI-resistant isolates had high AZT-AVI MIC. The rates of the inoculum effect for CAZ-AVI and AZT-AVI were 18% and 47%, respectively ( < 0.001). Interestingly, the frequency of the AZT-AVI inoculum effect was higher in than (64% vs. 8%, < 0.001). AZT-AVI is more active against CRE than CAZ-AVI, even in CP-CRE and CAZ-AVI-resistant isolates. The presence of a substantial inoculum effect may contribute to clinical failure in high-inoculum infections treated with AZT-AVI.
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http://dx.doi.org/10.3390/antibiotics9120912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765481PMC
December 2020

Superiority of Epstein-Barr Virus DNA in the Plasma Over Whole Blood for Prognostication of Extranodal NK/T Cell Lymphoma.

Front Oncol 2020 30;10:594692. Epub 2020 Nov 30.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: Extranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes.

Methods: We analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion.

Results: EBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79-9.97; =0.001) and OS (HR, 8.38; 95% CI, 3.03-23.19; <0.001) in the multivariate analysis. After treatment completion, positivity of plasma-EBV was independently associated with poor PFS (HR, 9.41; 95% CI, 2.27-39.02; =0.002) and OS (HR, 32.38; 95% CI, 3.25-322.56; =0.003), whereas no significant association was observed between WB-EBV status and survival outcomes.

Conclusions: Our results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL.
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http://dx.doi.org/10.3389/fonc.2020.594692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734249PMC
November 2020

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients With Carbapenem-Resistant Bacteremia.

Open Forum Infect Dis 2020 Oct 24;7(10):ofaa378. Epub 2020 Aug 24.

Departments of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Background: Carbapenem-resistant (CRAB) infection is associated with significant mortality, causing worldwide concern, yet there are limited data on contributing microbiological factors. This study aimed to identify the clinical and microbiologic risk factors for mortality in CRAB bacteremia.

Methods: Adult patients with monomicrobial CRAB bacteremia in a 2700-bed tertiary hospital between December 2012 and December 2018 were retrospectively enrolled. Risk factors for 30-day mortality were evaluated. All isolates collected on the first day of bacteremia were subjected to colistin susceptibility testing by broth microdilution and to genotyping by multilocus sequence typing.

Results: A total of 164 patients were enrolled, and 90 (55%) died within 30 days. The most common genotype among the isolates was ST191 (49%), and 12 isolates (7%) were resistant to colistin. Genotype, colistin minimum inhibitory concentration, and colistin resistance were not significantly associated with mortality, in contrast to several clinical factors. In multivariable analysis, ineradicable or not-eradicated focus (adjusted odds ratio [aOR], 4.92; 95% CI, 1.95-12.42; = .001), septic shock (aOR, 4.72; 95% CI, 2.12-10.49; < .001), and inappropriate antimicrobial therapy (aOR, 2.54; 95% CI, 1.05-6.16; = .04) were independent risk factors for mortality. Among antibiotic strategies, colistin combined with tigecycline or other antibiotics were significantly associated with lower mortality after adjustment for confounding factors.

Conclusions: Clinical factors such as the nature of the infection source and source control, severity of bacteremia, and appropriateness of antibiotics, rather than microbiological factors, contribute to mortality in CRAB bacteremia. A specific antibiotic combination may help improve outcomes.
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http://dx.doi.org/10.1093/ofid/ofaa378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539690PMC
October 2020

Prediction of HLA-DQ in Deceased Donors and its Clinical Significance in Kidney Transplantation.

Ann Lab Med 2021 Mar;41(2):190-197

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Background: HLA-DQ typing in deceased donors is not mandatory in Korea. Therefore, when patients develop DQ antibodies after kidney transplantation (KT) from deceased donor, it is impossible to determine whether they are donor-specific antibodies (DSA). We developed DQ prediction programs for the HLA gene and evaluated their clinical utility.

Methods: Two HLA-DQ prediction programs were developed: one based on Lewontin's linkage disequilibrium (LD) and haplotype frequency and the other on an artificial neural network (ANN). Low-resolution HLA-A, -B, -DR, and -DQ typing data of 5,603 Korean patients were analyzed in terms of haplotype frequency and used to develop an ANN DQ prediction program. Predicted DQ (pDQ) genotype accuracy was analyzed using the typed DQ data of 403 patients. pDQ DSA agreement, sensitivity, specificity, and false-negative rate was evaluated using 1,970 single-antigen bead assays performed on 885 KT recipients. The clinical significance of DQ and pDQ DSA was evaluated in 411 KT recipients.

Results: pDQ genotype accuracies were 75.4% (LD algorithm) and 75.7% (ANN). When the second most likely pDQ (LD algorithm) was also considered, the genotype accuracy increased to 92.6%. pDQ DSA (LD algorithm) agreement, sensitivity, specificity, and false-negative rate were 97.5%, 97.3%, 98.6%, and 2.4%, respectively. The antibody-mediated rejection treatment frequency was significantly higher in DQ or pDQ DSA-positive patients than in DQ or pDQ DSA-negative patients (<0.001).

Conclusions: Our DQ prediction programs showed good accuracy and could aid DQ DSA detection in patients who had undergone deceased donor KT without donor HLA-DQ typing.
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http://dx.doi.org/10.3343/alm.2021.41.2.190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591288PMC
March 2021

Letter to the Editor: The Interpretation of COVID-19 Seroprevalence Study Should Be Cautious.

J Korean Med Sci 2020 09 28;35(38):e338. Epub 2020 Sep 28.

Department of Laboratory Medicine, Seoul Medical Center, Seoul, Korea.

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http://dx.doi.org/10.3346/jkms.2020.35.e338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521961PMC
September 2020

Evaluation of Four Commercial Kits for SARS-CoV-2 Real-Time Reverse-Transcription Polymerase Chain Reaction Approved by Emergency-Use-Authorization in Korea.

Front Med (Lausanne) 2020 13;7:521. Epub 2020 Aug 13.

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

SARS-CoV-2 real-time reverse-transcription PCR (rRT-PCR) is the most effective testing system currently available to counter COVID-19 epidemics when potent treatments and vaccines are unavailable. Therefore, four SARS-CoV-2 rRT-PCR kits have been approved by the emergency-use-authorization (EUA) without clinical validation in Korea until March 15, 2020. This study evaluated the analytical and clinical performance of these kits. Allplex 2019-nCoV Real-time PCR (Seegene, Seoul, Korea), PowerChek 2019-nCoV (KogeneBiotech, Seoul), Real-Q 2019-nCoV Real-Time Detection (BioSewoom, Seoul), and StandardM nCoV Detection (SD BIOSENSOR, Osong, Korea) were evaluated. The limit of detection (LODs) of Allplex, PowerChek, and Real-Q was determined by testing the transcribed RNA of SARS-CoV-2 and the RNA of SARS-CoV Frankfurt1. A total of 27 consecutive samples comprising 13 sputum, 12 nasopharyngeal swab (NPS), 1 urine and 1 stool sample were collected from 2 COVID-19 patients for sensitivity analysis. Precision was assessed via daily tests of positive and negative controls in each kit for 5 d. Reproducibility was examined by repeating 21 samples and 10-fold dilutions of 14 samples in pairs using Allplex. Specificity was evaluated with 24 other respiratory virus-positive samples. LOD of Allplex, PowerChek, and Real-Q were 153.9, 84.1, and 80.6 copies/mL, respectively. The degrees of association between Cts and log viral concentrations by Allplex and PowerChek was expressed as y = -3.319 log (x) + 42.039 (R = 0.96) and y = -3.392 log(x) + 43.113 (R = 0.98), respectively. One or more of the 4 kits detected 20 out of 27 clinical samples positive. Of the 20 positive samples, the detection rates of positives for Allplex, PowerChek, Real-Q, and StandardM were 90.0, 82.3, 75.0, and 100.0%, respectively, but those of PowerChek and Real-Q would be 100% if out-of-cutoff Cts were counted as positives. Precision was 100%. Interpretation of Allplex results was reproducible when Ct of ≤33. All 4 kits showed no cross-reactivity with other respiratory viruses. Performance of the 4 kits indicated the suitability of these for diagnosis and follow-up testing of COVID-19. Laboratory doctors who initially implement these EUA kits must be able to interpret quality control parameters.
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http://dx.doi.org/10.3389/fmed.2020.00521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438443PMC
August 2020

Comparison of Nucleic Acid Amplification and IgM Tests for the Diagnosis of Mycoplasma pneumoniae Infection in Children During a Recent Korean Outbreak.

Lab Med 2020 Sep 4. Epub 2020 Sep 4.

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Objective: In the absence of standardized methods for Mycoplasma pneumoniae detection, we evaluated the diagnostic value of polymerase chain reaction (PCR) and IgM assays for detecting M. pneumoniae infection in children during a recent Korean outbreak.

Methods: The diagnostic performances of PCR and IgM assays for M. pneumoniae in 1,109 clinical specimens were evaluated by the Japanese Respiratory Society (JRS) scoring system as an interim reference standard.

Results: The level of agreement between both tests was fair. As analyzed by the JRS scoring system, the sensitivity of PCR was 45.2% in the group aged <5 years, 86.8% in the group aged 5 years to 10 years group, and 72.2% in the group aged 10 years to 18 years; the sensitivity of the IgM assay was 66.8%, 71.4%, and 55.6% in each group, respectively.

Conclusion: The sensitivity of PCR is relatively low but is superior to that of IgM assays such that diagnostic performance can be improved by both test methods in patients aged <5 years.
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http://dx.doi.org/10.1093/labmed/lmaa048DOI Listing
September 2020

Pooling Upper Respiratory Specimens for Rapid Mass Screening of COVID-19 by Real-Time RT-PCR.

Emerg Infect Dis 2020 10 26;26(10):2469-2472. Epub 2020 Aug 26.

To validate the specimen-pooling strategy for real-time reverse transcription PCR detection of severe acute respiratory syndrome coronavirus 2, we generated different pools including positive specimens, reflecting the distribution of cycle threshold values at initial diagnosis. Cumulative sensitivities of tested pool sizes suggest pooling of <6 specimens for surveillance by this method.
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http://dx.doi.org/10.3201/eid2610.201955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510748PMC
October 2020

Erratum: COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays.

Ann Lab Med 2021 01 25;41(1):126-127. Epub 2020 Aug 25.

Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Osong, Korea.

[This corrects the article on p. 439 in vol. 40.].
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http://dx.doi.org/10.3343/alm.2021.41.1.126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443524PMC
January 2021

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Int J Antimicrob Agents 2020 Oct 2;56(4):106126. Epub 2020 Aug 2.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Objectives: The aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia.

Materials And Methods: A retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase.

Results: Of 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality.

Conclusions: The results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.106126DOI Listing
October 2020

Decreased Incidence of Methicillin-Resistant Staphylococcus aureus Bacteremia in Intensive Care Units: a 10-Year Clinical, Microbiological, and Genotypic Analysis in a Tertiary Hospital.

Antimicrob Agents Chemother 2020 09 21;64(10). Epub 2020 Sep 21.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

There are limited long-term data on the trends in incidence and characteristics of methicillin-resistant (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 years using prospective cohort data. ICU-acquired bacteremia was defined as bacteremia (SAB) that occurred 48 h or more after ICU admission. MRSA isolates were collected and subjected to microbiological and genotypic analyses. A total of 529 SAB episodes were identified among 367,175 ICU patients. Of these episodes, 288 (54.4%) were ICU acquired, 238 (82.6%) of which were MRSAB. The incidence density of ICU-acquired MRSAB decreased from 1.32 per 1,000 patient-days to 0.19 per 1,000 patient-days (a decrease of 20% annually; 0.001 for trend), whereas that of non-ICU-acquired MRSAB fluctuated and did not decrease significantly. The decline in ICU-acquired MRSAB was due to lower catheter-related infection and less pneumonia. Rates of persistent bacteremia and 12-week mortality also fell significantly. A total of 183 isolates were collected from 238 ICU-acquired MRSAB cases. There were no significant changes in the geometric means of vancomycin MICs, vancomycin heteroresistance, or the sequence types of MRSA isolates over time. Chlorhexidine MICs decreased (0.001 for trend) in association with a decline in frequency of the or gene that was related to reductions in specific types. The incidence of MRSAB in ICUs has decreased dramatically over time, but most of the microbiological and genotypic characteristics of MRSA isolates have not changed.
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http://dx.doi.org/10.1128/AAC.01082-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508613PMC
September 2020

Nationwide External Quality Assessment of SARS-CoV-2 Molecular Testing, South Korea.

Emerg Infect Dis 2020 10 29;26(10):2353-2360. Epub 2020 Jul 29.

External quality assessment (EQA) is essential for ensuring reliable test results, especially when laboratories are using assays authorized for emergency use for newly emerging pathogens. We developed an EQA panel to assess the quality of real-time reverse transcription PCR assays being used in South Korea to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the participation of 23 public health organization laboratories and 95 nongovernmental laboratories involved in SARS-CoV-2 testing, we conducted qualitative and semiquantitative performance assessments by using pooled respiratory samples containing different viral loads of SARS-CoV-2 or human coronavirus OC43. A total of 110 (93.2%) laboratories reported correct results for all qualitative tests; 29 (24.6%) laboratories had >1 outliers according to cycle threshold values. Our EQA panel identified the potential weaknesses of currently available commercial reagent kits. The methodology we used can provide practical experience for those planning to conduct evaluations for testing of SARS-CoV-2 and other emerging pathogens in the future.
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http://dx.doi.org/10.3201/eid2610.202551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510727PMC
October 2020

Challenges and issues of SARS-CoV-2 pool testing.

Lancet Infect Dis 2020 11 14;20(11):1232-1233. Epub 2020 Jul 14.

Department of Laboratory Medicine, Seoul Medical Center, Seoul, South Korea. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(20)30516-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833783PMC
November 2020

Clinical characteristics and prognostic factors of extraintestinal infection caused by Clostridioides difficile: analysis of 60 consecutive cases.

Eur J Clin Microbiol Infect Dis 2020 Nov 6;39(11):2133-2141. Epub 2020 Jul 6.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, 05505, Republic of Korea.

Data regarding extraintestinal Clostridioides difficile infections (ECDIs) remain scarce and anecdotal. We conducted a retrospective cohort study to investigate characteristics and prognostic factors in patients with ECDI. From January 1997 through December 2018, 60 patients were enrolled and divided into three groups as follows: group A (gastrointestinal [GI] disruption caused by malignancy, n = 13); group B (GI disruption from causes other than malignancy, n = 25); group C (no GI disruption, n = 22). GI disruption was defined as compromised integrity of the GI tract caused by abdominal surgery, perforation, malignancy, enterocolitis, or bleeding. The incidence of ECDI was 2.53 per 100,000 admissions. The most common specimens yielded C. difficile were blood (36.7%), peritoneal fluid (20.0%), and abscesses (16.7%). Six patients (10.0%) had confirmed C. difficile enterocolitis, and 36 patients (60.0%) had a polymicrobial infection. C. difficile bacteremia was significantly more common in group A patients than those in groups B or C (53.8% vs. 48.0% vs. 13.6%, p = 0.02), as was the 30-day mortality rate (69.2% vs. 12.0% vs. 18.2%, respectively; p < 0.001). In multivariate analysis, group A (adjusted odds ratio [aOR], 17.32; 95% confidence interval [CI], 2.96-101.21; p = 0.002) and an age of > 65 years (aOR, 7.09; 95% CI, 1.31-38.45; p = 0.02) were independent risk factors for 30-day mortality. ECDI was uncommonly associated with C. difficile enterocolitis. Two factors, GI disruption caused by malignancy, and old age, were associated with significantly poorer short-term outcomes.
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http://dx.doi.org/10.1007/s10096-020-03975-9DOI Listing
November 2020

A predictive tool for identification of SARS-CoV-2 PCR-negative emergency department patients using routine test results.

J Clin Virol 2020 08 10;129:104502. Epub 2020 Jun 10.

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, USA; Clinical Microbiology Laboratory, Stanford University Medical Center, Palo Alto, CA, USA. Electronic address:

Background: Testing for COVID-19 remains limited in the United States and across the world. Poor allocation of limited testing resources leads to misutilization of health system resources, which complementary rapid testing tools could ameliorate.

Objective: To predict SARS-CoV-2 PCR positivity based on complete blood count components and patient sex.

Study Design: A retrospective case-control design for collection of data and a logistic regression prediction model was used. Participants were emergency department patients > 18 years old who had concurrent complete blood counts and SARS-CoV-2 PCR testing. 33 confirmed SARS-CoV-2 PCR positive and 357 negative patients at Stanford Health Care were used for model training. Validation cohorts consisted of emergency department patients > 18 years old who had concurrent complete blood counts and SARS-CoV-2 PCR testing in Northern California (41 PCR positive, 495 PCR negative), Seattle, Washington (40 PCR positive, 306 PCR negative), Chicago, Illinois (245 PCR positive, 1015 PCR negative), and South Korea (9 PCR positive, 236 PCR negative).

Results: A decision support tool that utilizes components of complete blood count and patient sex for prediction of SARS-CoV-2 PCR positivity demonstrated a C-statistic of 78 %, an optimized sensitivity of 93 %, and generalizability to other emergency department populations. By restricting PCR testing to predicted positive patients in a hypothetical scenario of 1000 patients requiring testing but testing resources limited to 60 % of patients, this tool would allow a 33 % increase in properly allocated resources.

Conclusions: A prediction tool based on complete blood count results can better allocate SARS-CoV-2 testing and other health care resources such as personal protective equipment during a pandemic surge.
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http://dx.doi.org/10.1016/j.jcv.2020.104502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286235PMC
August 2020

Comparison of the change in QuantiFERON-TB Gold Plus and QuantiFERON-TB Gold In-Tube results after preventive therapy for latent tuberculosis infection.

PLoS One 2020 16;15(6):e0234700. Epub 2020 Jun 16.

Division of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Background: We investigated changes in the interferon-γ levels before and after treatment of latent tuberculosis infection (LTBI) using QuantiFERON-TB Gold Plus (QFT-Plus) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The objective was to assess whether QFT-Plus could serve as a biomarker of LTBI treatment response.

Methods: We prospectively enrolled 44 individuals whose baseline QFT-GIT and QFT-Plus showed positive results at a tertiary referral center in South Korea between March 2017 and March 2018. The results of the QFT-Plus assay were defined as positive if either or both of the antigen tubes (TB1 and/or TB2) were positive. After LTBI treatment, both tests were repeated.

Results: The mean age of the participants was 47.6 years. The QFT-GIT and QFT-Plus assays revealed positive results in 42/44 (95.5%) and 41/44 (93.2%) participants after LTBI treatment, showing overall agreement of 93.2%, with a Cohen's kappa value of 0.37 (fair agreement). The differences between pre- and post-LTBI treatment interferon-γ levels were measured using the QFT-GIT and QFT-Plus assays. No significant differences were noted among the 3 values: the median difference in interferon-γ value with QFT-GIT, QFT-Plus TB1, and QFT-Plus TB2 was 0.211 IU/mL (IQR, -0.337-3.347), 0.025 IU/mL (IQR, -0.338-1.368), and 0.180 IU/mL (IQR, -0.490-2.278), respectively (P = 0.401).

Conclusion: The change in interferon-γ levels before and after LTBI treatment measured using the QFT-Plus assay showed a similar trend to that of the QFT-GIT assay. Considering that the QFT-GIT assay is not a useful biomarker of LTBI treatment response, QFT-Plus also appears not to be useful for this purpose.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234700PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297367PMC
August 2020

Quality of Ribonucleic Acid Extraction for Real-Time Reverse Transcription-PCR (rRT-PCR) of SARS-CoV-2: Importance of Internal Control Monitoring.

Ann Lab Med 2020 11 17;40(6):490-492. Epub 2020 Jun 17.

Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2020.40.6.490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295956PMC
November 2020

COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays.

Ann Lab Med 2020 11 17;40(6):439-447. Epub 2020 Jun 17.

Center for Laboratory Control of Infectious Diseases, Korea Centers for Disease Control and Prevention, Osong, Korea.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the "Guidelines for Laboratory Diagnosis of COVID-19 in Korea".
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http://dx.doi.org/10.3343/alm.2020.40.6.439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295959PMC
November 2020

Clinical characteristics and outcomes of Staphylococcus aureus bacteremia from a biliary source.

Eur J Clin Microbiol Infect Dis 2020 Oct 15;39(10):1951-1957. Epub 2020 Jun 15.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Staphylococcus aureus is a virulent gram-positive organism, which rarely involves the biliary tract. This study aimed to analyze the clinical characteristics and outcomes of S. aureus bacteremia (SAB) originating from the biliary tract by comparing them with those of catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. A matched case-control study within a prospective observational cohort of patients with SAB was conducted. Biliary SAB was defined as the isolation of S. aureus from blood cultures with symptoms and signs of biliary infection. Biliary SAB patients were matched (1:3) with the control groups: patients with catheter-related SAB and biliary Klebsiella pneumoniae bacteremia. Out of 1818 patients with SAB enrolled in the cohort, 42 (2%) had biliary SAB. Majority of these patients had solid tumors involving the pancreaticobiliary tract or liver, biliary drainage stent, and/or recent broad-spectrum antibiotic exposure. Patients with biliary SAB were more likely to have community-onset SAB, solid tumors, and lower APACHE II score than those with catheter-related SAB. They were less likely to have community-acquired infection and solid tumors and more likely to have lower Charlson comorbidity index and higher APACHE II score as compared with biliary K. pneumoniae bacteremia. The 12-week mortality in the biliary SAB group was higher than those in other control groups (60% vs. 20% and 14%). After adjusting for confounding factors, biliary SAB was independently associated with higher mortality. Biliary SAB is relatively rare. When it is clinically suspected, early aggressive treatment should be considered due to high mortality.
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http://dx.doi.org/10.1007/s10096-020-03940-6DOI Listing
October 2020

Update: Radiographic and CT Features of Viral Pneumonia.

Radiographics 2020 Jul-Aug;40(4):E8-E15. Epub 2020 Jun 5.

From the Department of Radiology and Research Institute of Radiology (H.J.K., J.C., K.H.D.), Division of Infectious Disease, Department of Internal Medicine (S.H.C.), and Department of Laboratory Medicine (H.S.), Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, South Korea.

.-Articles in the Update section provide current knowledge to supplement or update information found in full-length articles previously published in . Authors of the previously published article provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes. Articles in this section are published solely online and are linked to the original article.
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http://dx.doi.org/10.1148/rg.2020200097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336757PMC
June 2020

Re: Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19.

J Infect 2020 08 8;81(2):e79-e81. Epub 2020 May 8.

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Office for Infection Control, Asan Medical Center, Seoul, South Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206420PMC
August 2020

Guidelines for Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19) in Korea.

Ann Lab Med 2020 09;40(5):351-360

Center for Laboratory Control of Infectious Diseases, Centers for Disease Control and Prevention, Osong, Korea.

The outbreak of coronavirus disease 2019 (COVID-19), which began in December 2019, is still ongoing in Korea, with >9,000 confirmed cases as of March 25, 2020. COVID-19 is a severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, and real-time reverse transcription-PCR is currently the most reliable diagnostic method for COVID-19 around the world. Korean Society for Laboratory Medicine and the Korea Centers for Disease Prevention and Control propose guidelines for diagnosing COVID-19 in clinical laboratories in Korea. These guidelines are based on other related domestic and international guidelines, as well as expert opinions and include the selection of test subjects, selection of specimens, diagnostic methods, interpretation of test results, and biosafety.
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http://dx.doi.org/10.3343/alm.2020.40.5.351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169629PMC
September 2020

COVID-19 Testing in South Korea: Current Status and the Need for Faster Diagnostics.

Ann Lab Med 2020 Sep 31;40(5):349-350. Epub 2020 Mar 31.

Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3343/alm.2020.40.5.349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169622PMC
September 2020

Emergence of -Mediated Linezolid-Nonsusceptible in a Tertiary Care Hospital.

Ann Lab Med 2020 Jul;40(4):321-325

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

This study investigated resistance mechanisms and epidemiology of emerging linezolid-nonsusceptible (LNSEF) in a tertiary care hospital. LNSEF isolated from clinical samples were collected from November 2017 to June 2019. The isolates were investigated for linezolid resistance and the associated molecular mechanisms, including mutations of 23S rRNA domain V and acquisition of the or resistance gene. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing for the molecular typing of the isolates. Among 4,318 isolates, 10 (0.23%) were linezolid-nonsusceptible. All LNSEF isolates were -positive and -negative. Of these isolates, five were sequence type (ST) 476, two ST585, one ST16, one ST16-like, and one ST480. Six LNSEF isolates obtained in the first year clustered to three types in the PFGE analysis: two ST476 isolates of type A, two ST585 isolates of type B, and two ST16 or ST16-like isolates of type C. Seven cases were of community-onset and three were hospital acquired, but total of eight were healthcare-associated including five community-onset. None of the patients had a history of linezolid treatment, and in one patient, we detected linezolid-susceptible one month before LNSEF detection. In conclusion, heterogenous clones of -positive LNSEF emerged in the hospital mainly via community-onset.
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http://dx.doi.org/10.3343/alm.2020.40.4.321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054691PMC
July 2020