Background: The kinetics of neutralizing antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) play an important role in evaluating vaccine efficacy and durability, herd immunity, additional vaccination, and prediction models of immune protection against coronavirus disease 2019. Materials and Methods: Serum collection times were 4 and 8 weeks after 1st inoculation of AZD1222 (AstraZeneca, Cambridge, UK), and 2 and 16 weeks after 2nd inoculation with 12-week dosing intervals. Neutralizing antibody (Nab) titers were measured indirectly using commercially available R-FIND SARS-CoV-2 Neutralizing Antibody ELISA Kit (SG Medical Inc., Seoul, Korea). Possible influences of gender, age, and adverse events on neutralizing antibody titer were also investigated. Results: Nab titers (median inhibition %) started to decrease shortly after reaching peaks.This decrease was more pronounced in the elderly group (≥56 years) than in the young group (≤39 years) at 8 weeks (49.5% vs. 55.4%, P = 0.021) and 16 weeks (40.6% vs. 53.9%, P = 0.006) after the 1st and 2nd inoculation. And Nab titers were inversely correlated with age in the 8-week (r = -0.2091, P = 0.0284) and the 28-week group (r = -0.2811, P = 0.0029). Seropositive conversion of Nab reached 89.1% and 100% following 1st and 2nd inoculation. This 100% seropositivity was dropped sharply to 74.5% after 16 weeks. Compared to subjects without adverse events (51.8%), median inhibition was higher in subjects with one or more systemic adverse events (74.2%, P = 0.0203) or those with one or more local and systemic adverse events (77.1%, P = 0.0003). Conclusion Nab induced by AZD1222 (AstraZeneca, UK) vaccination started to degrade shortly after the production period. Nab titers were lower in the elderly than in younger group during the degradation period. This seems to be because the degradation process of Nab is more pronounced in the elderly. This may explain why the frequency of breakthrough infections, disease severity, and mortality were higher in the elderly and may require revaccination to ensure robust immunity.

Background: The purpose of this study was to investigate the association between antibiotic use and the antimicrobial resistance of gram-negative bacteria isolated from blood cultures in a pediatric population. Methods: From January 2014 to June 2018, the antibiotic resistance pattern of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa obtained from bacteremic patients aged ≤18 years hospitalized at Asan Medical Center Children's Hospital was analyzed and the parenteral antibiotic consumption data were retrieved. Results: During the study period, the blood culture was positive for K. pneumoniae (6.4%; 105/1,628), E. coli (5.6%; 91/1,628), P. aeruginosa (3.3%; 54/1,628), and A. baumannii (2.5%; 41/1,628), and the extended-spectrum antibiotic resistance rate of gram-negative bacteria was consistently high. The overall resistance rate of E. coliand K. pneumoniae to extendedspectrum cephalosporin was 49.3% and 54.4%, respectively. Carbapenem-resistant E. coli was first detected in 2014; its overall resistance rate to carbapenem was 5.3%. There was a linear correlation between the usage of 3rd generation cephalosporin and the resistance of A. baumannii (r2 =0.96, P=0.004) and carbapenem usage and the resistance of K. pneumoniae (r2 =0.79, P=0.045). Conclusions A positive linear correlation was observed between antibiotic resistance and the corresponding antibiotic usage in 3rd generation cephalosporin resistant A. baumanniiand carbapenem resistant K. pneumoniae. The judicious use of antibiotics in healthcare settings is important to minimize selection for extended-spectrum β-lactamase (ESBL) and carbapenem resistance in gram-negative bacteria.

Background: The purpose of this study was to investigate the association between antibiotic use and the antimicrobial resistance of gram-negative bacteria isolated from blood cultures in a pediatric population. Methods: From January 2014 to June 2018, the antibiotic resistance pattern of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa obtained from bacteremic patients aged ≤18 years hospitalized at Asan Medical Center Children's Hospital was analyzed and the parenteral antibiotic consumption data were retrieved. Results: During the study period, the blood culture was positive for K. pneumoniae (6.4%; 105/1,628), E. coli (5.6%; 91/1,628), P. aeruginosa (3.3%; 54/1,628), and A. baumannii (2.5%; 41/1,628), and the extended-spectrum antibiotic resistance rate of gram-negative bacteria was consistently high. The overall resistance rate of E. coliand K. pneumoniae to extendedspectrum cephalosporin was 49.3% and 54.4%, respectively. Carbapenem-resistant E. coli was first detected in 2014; its overall resistance rate to carbapenem was 5.3%. There was a linear correlation between the usage of 3rd generation cephalosporin and the resistance of A. baumannii (r2 =0.96, P=0.004) and carbapenem usage and the resistance of K. pneumoniae (r2 =0.79, P=0.045). Conclusions A positive linear correlation was observed between antibiotic resistance and the corresponding antibiotic usage in 3rd generation cephalosporin resistant A. baumanniiand carbapenem resistant K. pneumoniae. The judicious use of antibiotics in healthcare settings is important to minimize selection for extended-spectrum β-lactamase (ESBL) and carbapenem resistance in gram-negative bacteria.

Purpose: We investigated the trend of antibiotic susceptibility of Haemophilus influenzae over 5 consecutive years. Methods: We analyzed the antibiotic susceptibility of H. influenzae isolated from children aged <18 years, who were admitted to the Asan Medical Center Children's Hospital from March 2014 to April 2019. Antibiotic susceptibility of H. influenzae was determined by the disk diffusion test according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Results: Excluding duplicates, 69 isolates were obtained over the past 5 years. The median age of the patients was 5 years (range, 2.8–8.6 years). The antibiotic susceptibility patterns were as follows: ampicillin (AMP)-susceptible/amoxicillin-clavulanate (AMC)-susceptible (AS/ACS; n=15 [21.7%]), AMP-resistant/AMC-susceptible (AR/ACS; n=21 [30.4%]), and AMP-resistant/ AMC-resistant (AR/ACR; n=33 [47.8%]). The prevalence of isolates with AR/ACR phenotype tended to increase from 42.1% in 2014–2015 to 54.5% in 2018–2019 (P=0.342). Compared to 2014–2015, the resistance rates to cefuroxime and ceftriaxone in 2018–2019 increased from 31.6% to 77.3% and from 0.0% to 59.1%, respectively (P=0.003 and P<0.001, respectively). Conclusions Over the last 5 years, H. influenzae isolates with AR/ACR phenotype and ceftriaxone resistance were frequently observed at our institute. The incidence of resistance to cefuroxime and ceftriaxone has increased significantly.

Purpose: We investigated the trend of antibiotic susceptibility of Haemophilus influenzae over 5 consecutive years. Methods: We analyzed the antibiotic susceptibility of H. influenzae isolated from children aged <18 years, who were admitted to the Asan Medical Center Children's Hospital from March 2014 to April 2019. Antibiotic susceptibility of H. influenzae was determined by the disk diffusion test according to the European Committee on Antimicrobial Susceptibility Testing guidelines. Results: Excluding duplicates, 69 isolates were obtained over the past 5 years. The median age of the patients was 5 years (range, 2.8–8.6 years). The antibiotic susceptibility patterns were as follows: ampicillin (AMP)-susceptible/amoxicillin-clavulanate (AMC)-susceptible (AS/ACS; n=15 [21.7%]), AMP-resistant/AMC-susceptible (AR/ACS; n=21 [30.4%]), and AMP-resistant/ AMC-resistant (AR/ACR; n=33 [47.8%]). The prevalence of isolates with AR/ACR phenotype tended to increase from 42.1% in 2014–2015 to 54.5% in 2018–2019 (P=0.342). Compared to 2014–2015, the resistance rates to cefuroxime and ceftriaxone in 2018–2019 increased from 31.6% to 77.3% and from 0.0% to 59.1%, respectively (P=0.003 and P<0.001, respectively). Conclusions Over the last 5 years, H. influenzae isolates with AR/ACR phenotype and ceftriaxone resistance were frequently observed at our institute. The incidence of resistance to cefuroxime and ceftriaxone has increased significantly.

BACKGROUND: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. METHODS: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-Interact™online, and contraindicated, major, or moderate severity level in Micromedex® were included. SAS version 9.4 was used for data analysis. RESULTS: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. CONCLUSION: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.
Aged* ; Anti-Infective Agents ; Ciprofloxacin ; Cohort Studies ; Cross-Sectional Studies ; Drug Interactions ; Fluconazole ; Gliclazide ; Glipizide ; Glyburide ; Humans ; Hypoglycemia* ; Korea* ; Levofloxacin ; Male ; National Health Programs ; Ofloxacin ; Prescriptions ; Risk Factors ; Statistics as Topic ; Sulfonylurea Compounds

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) effectively reduce serum levels of low-density lipoprotein (LDL) and total cholesterol. High-intensity statins are recommended for all patients aged ≤75 with clinical atherosclerotic cardiovascular disease (ASCVD), diabetes mellitus aged 40–75 with ≥7.5% estimated 10-year ASCVD risk and LDL-C ≥190 mg/ dL. High-intensity statins associated with more frequent adverse events (AEs) compared to moderate- to low-intensity statins. The aim of this study was to compare AEs between high-intensity and moderate- to low-intensity statin group using the Korea Adverse Event Reporting System (KAERS) database. METHODS: Adults (≥18 years) with statin-associated AEs from July 2009-June 2014 were included. Only AEs classified as “certain”, “probable” and “possible” based on the WHO-Uppsala Monitoring Center criteria were analyzed. RESULTS: In total, 247 AEs from 196 patients [high-intensity statin group (HG), n = 25 (13%); moderate- to lowintensity statin group (MLG), n = 171 (87%)] were included. Mean age was higher in HG compared with MLG (67 ± 14 vs 62 ± 12). The HG showed a significant higher frequency of liver/biliary system disorders (37% vs 14%, p = 0.001). Hepatic function abnormal was reported more frequently in HG compared to MLG (26% vs 9%, p = 0.006). CONCLUSION: According to KAERS data, liver/biliary system disorders were more frequently reported in HG compared to MLG.
Adult ; Cardiovascular Diseases ; Cholesterol ; Coenzyme A ; Diabetes Mellitus ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Korea ; Lipoproteins ; Oxidoreductases

PURPOSE: Parenteral nutrition (PN) is known to provide therapeutic beneficial improvements in malnourished patients for whom enteral nutrition is not feasible. The objective of this study was to investigate the current clinical characteristics and utilization of PN in Korea. METHODS: We analyzed the Health Insurance Review Agency National Inpatients Sample database from 2014 to 2016, which included 13% of all hospitalized patients in Korea. Adult patients aged 20 years or older and receiving premixed multi-chamber bag containing PN were included for this study. Patient characteristics, admission type, primary diagnosis, and hospital demographics were evaluated. SAS version 9.4 was used for data analysis. RESULTS: From 2014 to 2016, 149,504 patients received premixed PN, with 226,281 PN prescriptions being written. The mean patient age was 65.0 years, and 81,876 patients (54.8%) were male. Premixed 3-chamber bag and 2-chamber bag PN solutions were utilized in 131,808 (88.2%) and 32,033 (21.4%) patients, respectively. The number of patients hospitalized through the emergency department were 70,693 (47.3%), whereas 43,125 patients (28.8%) were administered PN in intensive care units. In the adult PN patients, the highest primary diagnosis was malignant neoplasm of the stomach (8,911, 6.0%), followed by organism unspecified pneumonia (7,008, 4.7%), and gastroenteritis and colitis of unspecified origin (6,381, 4.3%). Overall, 34% of adult PN patients were diagnosed with malignancies, the most common being neoplasm of the stomach (17.7%), neoplasm of bronchus/lung (11.2%), neoplasm of colon (11.1%), and neoplasm of liver/intrahepatic bile ducts (10.0%). PN solutions were most frequently administered in the metropolitan area (55.0%) and in hospitals with more than 1,000 beds (23.6%). CONCLUSION: PN was commonly administered in older patients, with primary diagnosis of malignancy in a significant number of cases. This study is the first large-scale description of PN-prescribing patterns in real-world clinical practice in South Korea.
Adult* ; Bile Ducts ; Colitis ; Colon ; Demography ; Diagnosis ; Emergency Service, Hospital ; Enteral Nutrition ; Gastroenteritis ; Humans ; Inpatients ; Insurance, Health ; Intensive Care Units ; Korea* ; Male ; Nutritional Support ; Parenteral Nutrition* ; Pneumonia ; Prescriptions ; Statistics as Topic ; Stomach

PURPOSE: This study aimed to identify the view of life and death among ICU nurses and to analyze the problems related to end-of-life care in the current ICUs. METHODS: A descriptive study design was used. The participants were 975 nurses working in the intensive care units of 16 general hospitals. Using a descriptive survey design, data were collected from August to December in 2016 and were analyzed using descriptive statistics, t-test, ANOVA, correlation analysis, and multiple regression analysis. RESULTS: As a result of a correlation analysis of the data, Death perception had a significant positive correlation with EOL of nursing attitudes(r=.100, p=.002), and negative correlation with EOL stress care(r=−.221, p= < .001). The regression model explained for individual characteristics in the model, age(β=.126, p < .001) and death perception(β=.182, p < .001), Satisfaction of the EOL care(β=.173, p < .001), Healing training needs on the EOL(β=−.144, p < .001) were the most influential factors for EOL stress. CONCLUSION: Results reveal that ICU nurses have a moderate level of EOL stress, and that individual, age, death perception, Satisfaction of the EOL care, Healing traning needs on the EOL relevant in ICU nurses' EOL stress. Programs or interventions to reduce EOL stress and to should be developed taking into account these multidimensional factors.
Critical Care ; Hospitals, General ; Intensive Care Units ; Nursing ; Stress, Psychological ; Terminal Care

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.
Creatine Kinase, MM Form ; Gene Expression ; Histone Deacetylase 1 ; Histone Deacetylases ; Histones ; Luciferases ; Muscle Cells ; Muscle Development ; Myoblasts ; Myoblasts, Skeletal ; Sumoylation ; Transfection