1.Implementing antimicrobial stewardship: lessons and perspectives from a university-affiliated tertiary hospital in Korea
Soo Jin LEE ; Raeseok LEE ; Sung-Yeon CHO ; Dukhee NHO ; Hye Lim AHN ; Dong-Gun LEE
The Korean Journal of Internal Medicine 2024;39(3):399-412
Antimicrobial stewardship programs (ASPs) can lower antibiotic use, decrease medical expenses, prevent the emergence of resistant bacteria, and enhance treatment for infectious diseases. This study summarizes the stepwise implementation and effects of ASPs in a single university-affiliated tertiary care hospital in Korea; it also presents future directions and challenges in resource-limited settings. At the study hospital, the core elements of the ASP such as leadership commitment, accountability, and operating system were established in 2000, then strengthened by the formation of the Antimicrobial Stewardship (AMS) Team in 2018. The actions of ASPs entail key components including a computerized restrictive antibiotic prescription system, prospective audit, post-prescription review through quantitative and qualitative intervention, and pharmacy-based interventions to optimize antibiotic usage. The AMS Team regularly tracked antibiotic use, the effects of interventions, and the resistance patterns of pathogens in the hospital. The reporting system was enhanced and standardized by participation in the Korea National Antimicrobial Use Analysis System, and educational efforts are ongoing. Stepwise implementation of the ASP and the efforts of the AMS Team have led to a substantial reduction in the overall consumption of antibiotics, particularly regarding injectables, and optimization of antibiotic use. Our experience highlights the importance of leadership, accountability, institution-specific interventions, and the AMS Team.
2.Advances in prophylaxis and treatment of invasive fungal infections:perspectives on hematologic diseases
Hyojin AHN ; Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE
Blood Research 2022;57(S1):S101-S111
Invasive fungal infections (IFIs) are common causes of mortality and morbidity in patients with hematologic diseases. Delayed initiation of antifungal treatment is related to mortality. Aspergillus sp. is the leading cause of IFI followed by Candida sp. Diagnosis is often challenging owing to variable conditions related to underlying diseases. Clinical suspect and prompt management is important. Imaging, biopsy, and non-culture-based tests must be considered together. New diagnostic procedures have been improved, including antigen-based assays and molecular detection of fungal DNA. Among hematologic diseases, patients with acute myeloid leukemia, myelodysplastic syndrome, recipients of hematopoietic stem cell transplantation are at high risk for IFIs. Antifungal prophylaxis is recommended for these high-risk patients. There are continuous attempts to achieve ideal management of IFIs. Scoring system for quality control has been developed with important recommendations of current guidelines. Higher adherence to guidelines is related to decreased mortality in IFIs.
3.High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide PopulationBased Matched Cohort Study
Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE ; Dukhee NHO
Journal of Korean Medical Science 2024;39(34):e255-
Background:
Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain.
Methods:
We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA).
Results:
During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25–1.76) and 90 days (aHR, 1.63; CI, 1.44–1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79–1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94–9.43).
Conclusion
Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.
4.High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide PopulationBased Matched Cohort Study
Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE ; Dukhee NHO
Journal of Korean Medical Science 2024;39(34):e255-
Background:
Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain.
Methods:
We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA).
Results:
During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25–1.76) and 90 days (aHR, 1.63; CI, 1.44–1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79–1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94–9.43).
Conclusion
Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.
5.High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide PopulationBased Matched Cohort Study
Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE ; Dukhee NHO
Journal of Korean Medical Science 2024;39(34):e255-
Background:
Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain.
Methods:
We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA).
Results:
During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25–1.76) and 90 days (aHR, 1.63; CI, 1.44–1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79–1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94–9.43).
Conclusion
Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.
6.High-Dose Corticosteroid Use in Severe to Critically Ill Patients With COVID-19: A Nationwide PopulationBased Matched Cohort Study
Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE ; Dukhee NHO
Journal of Korean Medical Science 2024;39(34):e255-
Background:
Systemic corticosteroids have become the standard of care for severe to critically ill patients with coronavirus disease 2019 (COVID-19). However, the real-world efficacy and safety outcomes associated with a higher dose of corticosteroids remain uncertain.
Methods:
We conducted a nationwide, population-based, matched cohort study of severe to critically ill adult patients with COVID-19 between January 2020 and June 2021 in Korea using the National Health Information Database. Patients using systemic corticosteroids were included and high-dose corticosteroid use was defined as a daily mean prescribed dose of more than 6 mg of dexamethasone. We then employed a proportional hazard regression model to identify prognostic factors for 28-day all-cause mortality and conducted a Fine and Gray regression model to assess risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA).
Results:
During the study period, 102,304 patients with COVID-19 were screened, 5,754 met the eligibility criteria, and 2,138 were successfully matched. The mean prescribed daily dose was 4.2 mg and 13.4 mg in the standard- and high-dose groups, respectively, and the mean duration of use was not different between the groups. High-dose corticosteroid use independently increased all-cause mortality at 28 days (adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.25–1.76) and 90 days (aHR, 1.63; CI, 1.44–1.85) after admission. Subgroup analysis revealed a statistically significant elevation in the risk of mortality among patients using low-flow or high-flow nasal cannulas, with aHRs of 1.41 and 1.46, respectively. No significant impact of high-dose steroids was observed, even in patients who underwent mechanical ventilation at 28 days (aHR, 1.17; CI, 0.79–1.72). As a safety outcome, high-dose corticosteroid use showed an association with the development of CAPA (aHR, 2.97; 95% CI, 0.94–9.43).
Conclusion
Among severe to critically ill patients with COVID-19, high-dose corticosteroid use was associated with increased 28-day all-cause mortality and showed a trend toward the development of CAPA.
7.Clinical Characteristics and Antimicrobial Susceptibility Trends in Citrobacter Bacteremia: An 11-Year Single-Center Experience
Raeseok LEE ; Su Mi CHOI ; Sung Jin JO ; Jehoon LEE ; Sung Yeon CHO ; Si Hyun KIM ; Dong Gun LEE ; Hyeong Seok JEONG
Infection and Chemotherapy 2019;51(1):1-9
BACKGROUND:
Recently, Citrobacter freundii bacteremia outbreak in a neonatal intensive care unit has attracted public attention in Korea. However, Citrobacter bacteremia is uncommon and usually occurs in patients with underlying diseases such as malignancy and hepatobiliary diseases. Increase in resistance and emerging of multidrug resistance among Citrobacter species have gradually been reported. The aim of this study was to investigate the clinical characteristics and outcome of C. freundii and non-freundii bacteremia and antimicrobial susceptibility trends.
MATERIALS AND METHODS:
We reviewed the medical records of patients with Citrobacter bacteremia at St. Mary's Hospital, from 2007 to 2017.
RESULTS:
A total of 43 patients with a median age of 72 (24-93) years was identified and 90.7% of them had comorbidities. Twenty-nine (67.4%) patients had C. freundii bacteremia while 14 had non-freundii bacteremia (six of C. braakii, five of C. koseri, two of C. amalonaticus and one of C. youngae). A total of 26 (51.2%) patients had community-acquired infection and intra-abdominal infection including hepatobiliary tract was the most common portal of entry (24/43, 55.8%). Moreover, hepatobiliary tract was the leading primary site of nosocomial infection (9/17, 52.9%). Polymicrobial bacteremia was observed in 21 (48.8%) patients. The percentages of Citrobacter species susceptible to ampicillin, amikacin, aztreonam, cefazolin, cefoxitin, cefotaxime, cefepime, piperacillin-tazobactam, ciprofloxacin, and imipenem were 9.5%, 97.6%, 73.8%, 9.5%, 14.3%, 71.4%, 92.9%, 83.3%, 83.3% and 100%, respectively. The resistance rate did not increase during the study period. Of 39 patients treated with antibiotics, 36 (92.3%) received appropriate empirical antibiotics. Overall mortality was 18.6%. High Charlson comorbidity index and Pitt bacteremia score were significant risk factors for death in univariate analysis and showed trends in the multivariate analysis. No significant difference in clinical features and antimicrobial susceptibility rate was observed between C. freundii and non-freundii bacteremia.
CONCLUSION
Citrobacter bacteremia was predominant in the elderly with comorbidities, while no pediatric case was observed. Hepatobiliary tract is the leading primary focus of bacteremia both in community-acquired and nosocomial infection. The rate of susceptibility to antibiotics has not changed in the last 11 years.
8.Migratory Pneumonia in Prolonged SARS-CoV-2 Infection in Patients Treated With B-cell Depletion Therapies for B-cell Lymphoma
Jongmin LEE ; Raeseok LEE ; Kyongmin Sarah BECK ; Dae Hee HAN ; Gi June MIN ; Suyon CHANG ; Jung Im JUNG ; Dong-Gun LEE
Korean Journal of Radiology 2023;24(4):362-370
Objective:
To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms.
Materials and Methods:
From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37–71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features.
Results:
All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, followup CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25.
Conclusion
COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.
10.Bloodstream Infections in Patients with Hematologic Diseases: Causative Organisms and Factors Associated with Resistance
Hyeah CHOI ; Hyojin AHN ; Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE
Infection and Chemotherapy 2022;54(2):340-352
Background:
Patients with hematologic diseases are at high risk of bloodstream infections (BSIs). This study aimed to analyze clinical features and distributions of microorganisms in patients with hematologic diseases presenting at a tertiary care university-affiliated hospital in Korea.
Materials and Methods:
We retrospectively reviewed all BSI episodes recorded in patient medical records at two hematologic wards of the Catholic Hematology Hospital from January to December 2020. Our aim was to analyze demographic and clinical characteristics relevant to BSIs. We also described the antimicrobial resistance patterns of the major pathogens identified in this study, and evaluated risk factors for extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae isolates and for vancomycin resistance in enterococcal isolates.
Results:
A total of 380 BSI episodes were identified in 334 patients over the course of 1 year (monomicrobial BSI episodes, 86.1%; polymicrobial BSI episodes, 13.9%). Gram-negative bacteria accounted for 242 isolates (54.8%). The most frequently isolated Gram-negative bacteria isolates were Escherichia coli (107 [24.2%]) followed by Klebsiella spp. (72 [16.3%]), Pseudomonas spp. (21 [4.8%]), and Enterobacter spp. (12 [2.7%]). The most commonly identified Gram-positive bacteria were Enterococcus spp. (72 [16.3%]) followed by viridans streptococci (54 [12.2%]), coagulase-negative staphylococci (CoNS) (24 [5.4%]), and Corynebacterium spp. (22 [5.0%]). ESBL-producing Enterobacteriaceae accounted for 25.1% of the total distribution. Among 54 Enterococcus faecium isolates, 100.0% were resistant to ampicillin and 55.6% showed resistance to vancomycin, while 100.0% (n = 12) of Enterococcus faecalis isolates were susceptible to ampicillin and vancomycin, respectively. Use of ciprofloxacin prophylaxis (odds ratio: 5.20; 95% confidence interval: 1.11 - 24.34; P = 0.04) was an independent risk factor for ESBL production in Enterobacteriaceae BSIs.
Conclusion
Compared with the results of a previous study conducted at the same institution, our findings demonstrated that Gram-negative bacteria remained dominant pathogens in BSIs occurring in patients with hematologic diseases. Our findings also demonstrated a comparatively decreased prevalence of ESBL-producing Enterobacteriaceae in the evaluated BSIs. However, the prevalence of enterococcal BSIs had not decreased, and the proportion of vfancomycin-resistant Enterococcus isolates from E. faecium BSIs had increased. In addition, we found that ciprofloxacin prophylaxis was statistically significantly associated with ESBL production in Enterobacteriaceae BSIs. We conclude that, in order to avoid critical complications and to reduce the burden of antimicrobial-resistant organisms in patients with hematologic diseases, it is necessary to conduct periodic examinations evaluating changes in BSI epidemiology within a single medical center.