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.How Should Cytomegalovirus Infection Be Managed in Allogeneic Hematopoietic Stem Cell Transplant Recipients?A Clinical Grand Round
Dukhee NHO ; Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE
Infection and Chemotherapy 2025;57(1):38-44
Cytomegalovirus (CMV) is a significant concern for patients with allogeneic hematopoietic cell transplantation (alloHCT). CMV management differs between institutions due to the lack of local guidelines. Here, we describe a case of refractory/resistant CMV infection treated using our institution's CMV management protocol. A 59-year-old woman who underwent allo-HCT was treated for CMV reactivation. Despite 3 months of valganciclovir administration, serum CMV level surged. CMV gene mutation test revealed a ganciclovir-resistant A594V mutation in the UL97 gene.Treatment was switched to foscarnet until the drug became unavailable nationwide. During the foscarnet shortage, cidofovir was used, leading to a decline in CMV levels when foscarnet was reintroduced and used for 2 months.Following allo-HCT, CMV prophylaxis with letermovir is crucial to prevent reactivation in seropositive recipients.CMV titers should be monitored frequently after allo-HCT. The cutoff value for preemptive therapy varies across institutions, with ganciclovir/valganciclovir usually administered as first-line therapy. Maribavir is an option in cases of ganciclovir/valganciclovir resistance or intolerance. CMV gene mutations should be examined in patients with suspected resistance after 2 weeks of appropriate treatment. This case was discussed at the Clinical Grand Round of the Annual Conference of the Korean Society of Infectious Diseases on November 2, 2023.
4.How Should Cytomegalovirus Infection Be Managed in Allogeneic Hematopoietic Stem Cell Transplant Recipients?A Clinical Grand Round
Dukhee NHO ; Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE
Infection and Chemotherapy 2025;57(1):38-44
Cytomegalovirus (CMV) is a significant concern for patients with allogeneic hematopoietic cell transplantation (alloHCT). CMV management differs between institutions due to the lack of local guidelines. Here, we describe a case of refractory/resistant CMV infection treated using our institution's CMV management protocol. A 59-year-old woman who underwent allo-HCT was treated for CMV reactivation. Despite 3 months of valganciclovir administration, serum CMV level surged. CMV gene mutation test revealed a ganciclovir-resistant A594V mutation in the UL97 gene.Treatment was switched to foscarnet until the drug became unavailable nationwide. During the foscarnet shortage, cidofovir was used, leading to a decline in CMV levels when foscarnet was reintroduced and used for 2 months.Following allo-HCT, CMV prophylaxis with letermovir is crucial to prevent reactivation in seropositive recipients.CMV titers should be monitored frequently after allo-HCT. The cutoff value for preemptive therapy varies across institutions, with ganciclovir/valganciclovir usually administered as first-line therapy. Maribavir is an option in cases of ganciclovir/valganciclovir resistance or intolerance. CMV gene mutations should be examined in patients with suspected resistance after 2 weeks of appropriate treatment. This case was discussed at the Clinical Grand Round of the Annual Conference of the Korean Society of Infectious Diseases on November 2, 2023.
5.How Should Cytomegalovirus Infection Be Managed in Allogeneic Hematopoietic Stem Cell Transplant Recipients?A Clinical Grand Round
Dukhee NHO ; Raeseok LEE ; Sung-Yeon CHO ; Dong-Gun LEE
Infection and Chemotherapy 2025;57(1):38-44
Cytomegalovirus (CMV) is a significant concern for patients with allogeneic hematopoietic cell transplantation (alloHCT). CMV management differs between institutions due to the lack of local guidelines. Here, we describe a case of refractory/resistant CMV infection treated using our institution's CMV management protocol. A 59-year-old woman who underwent allo-HCT was treated for CMV reactivation. Despite 3 months of valganciclovir administration, serum CMV level surged. CMV gene mutation test revealed a ganciclovir-resistant A594V mutation in the UL97 gene.Treatment was switched to foscarnet until the drug became unavailable nationwide. During the foscarnet shortage, cidofovir was used, leading to a decline in CMV levels when foscarnet was reintroduced and used for 2 months.Following allo-HCT, CMV prophylaxis with letermovir is crucial to prevent reactivation in seropositive recipients.CMV titers should be monitored frequently after allo-HCT. The cutoff value for preemptive therapy varies across institutions, with ganciclovir/valganciclovir usually administered as first-line therapy. Maribavir is an option in cases of ganciclovir/valganciclovir resistance or intolerance. CMV gene mutations should be examined in patients with suspected resistance after 2 weeks of appropriate treatment. This case was discussed at the Clinical Grand Round of the Annual Conference of the Korean Society of Infectious Diseases on November 2, 2023.
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.Hepatitis B surface antigen reverse seroconversion after hematopoietic stem cell transplantation according to the baseline serological marker levels and vaccination status:a single‑center database analysis
Soo Young KANG ; Heejoo KO ; Raeseok LEE ; Sung‑Soo PARK ; Seunghoon HAN
Blood Research 2024;59():31-
Purpose:
Hepatitis B is a major prognostic factor after hematopoietic stem cell transplantation (HSCT). Currently, no consensus exists regarding the management of various scenarios that can lead to reverse seroconversion of the hepatitis B surface antigen (HBsAg-RS). This study focused on HBsAg-RS, which serves as an indicator of active hepatitis, and aimed to obtain exploratory information on the associated patient and treatment factors.
Methods:
This single-center retrospective study utilized clinical data extracted from the electronic medical records of Seoul St. Mary’s Hospital, Korea. Patients who underwent HSCT between January 2013 and December 2018 and tested negative for hepatitis B surface antigen (HBsAg) before undergoing HSCT were included. The associations between HBsAg-RS and demographic information, baseline hepatitis B serological markers, and vaccination status were statistically analyzed.
Results:
This study included 1,344 patients, of whom 83.3% tested positive for the hepatitis B surface antibody (HBsAb) during HSCT. HBsAg-RS occurred in 2.2% of HBsAb-negative patients and 3.0% of HBsAb-positive patients, indicating no significant difference in reactivation rates according to HBsAb status. However, positivity for hepatitis B core antibody (HBcAb) was significantly associated with hepatitis B reactivation (HBsAg-RS rate: 8.0%). The vaccination rates were highest in patients who were negative for both HBsAb and HBcAb and had a transient protective effect.
Conclusion
The sufficient patient population enabled the identification of an association between baseline HBcAb positivity and the development of HBsAg-RS. Further prospective studies are warranted to determine optimal vac‑ cination strategies for preventing HBsAg-RS.
8.Hepatitis B surface antigen reverse seroconversion after hematopoietic stem cell transplantation according to the baseline serological marker levels and vaccination status:a single‑center database analysis
Soo Young KANG ; Heejoo KO ; Raeseok LEE ; Sung‑Soo PARK ; Seunghoon HAN
Blood Research 2024;59():31-
Purpose:
Hepatitis B is a major prognostic factor after hematopoietic stem cell transplantation (HSCT). Currently, no consensus exists regarding the management of various scenarios that can lead to reverse seroconversion of the hepatitis B surface antigen (HBsAg-RS). This study focused on HBsAg-RS, which serves as an indicator of active hepatitis, and aimed to obtain exploratory information on the associated patient and treatment factors.
Methods:
This single-center retrospective study utilized clinical data extracted from the electronic medical records of Seoul St. Mary’s Hospital, Korea. Patients who underwent HSCT between January 2013 and December 2018 and tested negative for hepatitis B surface antigen (HBsAg) before undergoing HSCT were included. The associations between HBsAg-RS and demographic information, baseline hepatitis B serological markers, and vaccination status were statistically analyzed.
Results:
This study included 1,344 patients, of whom 83.3% tested positive for the hepatitis B surface antibody (HBsAb) during HSCT. HBsAg-RS occurred in 2.2% of HBsAb-negative patients and 3.0% of HBsAb-positive patients, indicating no significant difference in reactivation rates according to HBsAb status. However, positivity for hepatitis B core antibody (HBcAb) was significantly associated with hepatitis B reactivation (HBsAg-RS rate: 8.0%). The vaccination rates were highest in patients who were negative for both HBsAb and HBcAb and had a transient protective effect.
Conclusion
The sufficient patient population enabled the identification of an association between baseline HBcAb positivity and the development of HBsAg-RS. Further prospective studies are warranted to determine optimal vac‑ cination strategies for preventing HBsAg-RS.
9.Hepatitis B surface antigen reverse seroconversion after hematopoietic stem cell transplantation according to the baseline serological marker levels and vaccination status:a single‑center database analysis
Soo Young KANG ; Heejoo KO ; Raeseok LEE ; Sung‑Soo PARK ; Seunghoon HAN
Blood Research 2024;59():31-
Purpose:
Hepatitis B is a major prognostic factor after hematopoietic stem cell transplantation (HSCT). Currently, no consensus exists regarding the management of various scenarios that can lead to reverse seroconversion of the hepatitis B surface antigen (HBsAg-RS). This study focused on HBsAg-RS, which serves as an indicator of active hepatitis, and aimed to obtain exploratory information on the associated patient and treatment factors.
Methods:
This single-center retrospective study utilized clinical data extracted from the electronic medical records of Seoul St. Mary’s Hospital, Korea. Patients who underwent HSCT between January 2013 and December 2018 and tested negative for hepatitis B surface antigen (HBsAg) before undergoing HSCT were included. The associations between HBsAg-RS and demographic information, baseline hepatitis B serological markers, and vaccination status were statistically analyzed.
Results:
This study included 1,344 patients, of whom 83.3% tested positive for the hepatitis B surface antibody (HBsAb) during HSCT. HBsAg-RS occurred in 2.2% of HBsAb-negative patients and 3.0% of HBsAb-positive patients, indicating no significant difference in reactivation rates according to HBsAb status. However, positivity for hepatitis B core antibody (HBcAb) was significantly associated with hepatitis B reactivation (HBsAg-RS rate: 8.0%). The vaccination rates were highest in patients who were negative for both HBsAb and HBcAb and had a transient protective effect.
Conclusion
The sufficient patient population enabled the identification of an association between baseline HBcAb positivity and the development of HBsAg-RS. Further prospective studies are warranted to determine optimal vac‑ cination strategies for preventing HBsAg-RS.
10.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.