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Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
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The identification of antimicrobial use patterns is essential for determining key targets for antimicrobial stewardship interventions and evaluating the effectiveness thereof. Accurately identifying antimicrobial use patterns requires quantitative evaluation, which focuses on measuring the quantity and frequency of antimicrobial use, and qualitative evaluation, which assesses the appropriateness, effectiveness, and potential side effects of antimicrobial prescriptions. This paper summarizes the quantitative and qualitative methods used to evaluate antimicrobials, drawing insights from overseas and domestic cases.
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The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC 0-24 ) of 400 to 600 mg*h/L for serious methicillinresistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC 0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC 0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC 0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.
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Background@#Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. @*Methods@#Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. @*Results@#Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). @*Conclusion@#The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.
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Background@#Although coronavirus disease 2019 (COVID-19) is a viral infection, antibiotics are often prescribed due to concerns about accompanying bacterial infection. Therefore, we aimed to analyze the number of patients with COVID-19 who received antibiotic prescriptions, as well as factors that influenced antibiotics prescription, using the National Health Insurance System database. @*Methods@#We retrospectively reviewed claims data for adults aged ≥ 19 years hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to the National Institutes of Health guidelines for severity classification, we calculated the proportion of patients who received antibiotics and the number of days of therapy per 1,000 patient-days. Factors contributing to antibiotic use were determined using linear regression analysis. In addition, antibiotic prescription data for patients with influenza hospitalized from 2018 to 2021 were compared with those for patients with COVID-19, using an integrated database from Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort (K-COV-N cohort), which was partially adjusted and obtained from October 2020 to December 2021. @*Results@#Of the 55,228 patients, 46.6% were males, 55.9% were aged ≥ 50 years, and most patients (88.7%) had no underlying diseases. The majority (84.3%; n = 46,576) were classified as having mild-to-moderate illness, with 11.2% (n = 6,168) and 4.5% (n = 2,484) having severe and critical illness, respectively. Antibiotics were prescribed to 27.3% (n = 15,081) of the total study population, and to 73.8%, 87.6%, and 17.9% of patients with severe, critical, and mild-to-moderate illness, respectively. Fluoroquinolones were the most commonly prescribed antibiotics (15.1%; n = 8,348), followed by third-generation cephalosporins (10.4%; n = 5,729) and beta-lactam/beta-lactamase inhibitors (6.9%; n = 3,822). Older age, COVID-19 severity, and underlying medical conditions contributed significantly to antibiotic prescription requirement. The antibiotic use rate was higher in the influenza group (57.1%) than in the total COVID-19 patient group (21.2%), and higher in severe-to-critical COVID-19 cases (66.6%) than in influenza cases. @*Conclusion@#Although most patients with COVID-19 had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of antibiotics is necessary for patients with COVID-19, considering the severity of disease and risk of bacterial co-infection.
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A case of persistent Ralstonia mannitolilytica bacteremia in the neonatal intensive care unit prompted source investigation due to its rarity. After an extensive investigation, a contaminated ultrasonic nebulizer was identified as the source, and the infection was controlled by removing the source. This study emphasizes the importance of further investigations, even in single cases of rare pathogens.
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Background@#The Korea National Antimicrobial Use Analysis System (KONAS), a benchmarking system for antimicrobial use in hospitals, provides Korean Standardized Antimicrobial Administration Ratio (K-SAAR) for benchmarking. This article describes K-SAAR predictive models to enhance the understanding of K-SAAR, an important benchmarking strategy for antimicrobial usage in KONAS. @*Methods@#We obtained medical insurance claims data for all hospitalized patients aged ≥ 28 days in all secondary and tertiary care hospitals in South Korea (n = 347) from January 2019 to December 2019 from the Health Insurance Review & Assessment Service. Modeling was performed to derive a prediction value for antimicrobial use in each institution, which corresponded to the denominator value for calculating K-SAAR. The prediction values of antimicrobial use were modeled separately for each category, for all inpatients and adult patients (aged ≥ 15 years), using stepwise negative binomial regression. @*Results@#The final models for each antimicrobial category were adjusted for different significant risk factors. In the K-SAAR models of all aged patients as well as adult patients, most antimicrobial categories included the number of hospital beds and the number of operations as significant factors, while some antimicrobial categories included mean age for inpatients, hospital type, and the number of patients transferred from other hospitals as significant factors. @*Conclusion@#We developed a model to predict antimicrobial use rates in Korean hospitals, and the model was used as the denominator of the K-SAAR.
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Background@#As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. @*Results@#In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. @*Conclusions@#This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.
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Background@#The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). @*Methods@#An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. @*Results@#The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available.Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. @*Conclusion@#Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.
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The STANDARD™ M10 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) assay (M10 assay) (SD Biosensor Inc., Suwon, Korea) is a rapid, fully-automated, cartridgetype molecular diagnostic assay that detects SARS-CoV-2 RNA using primers and probes for each target gene (ORF1ab gene, E gene). This study evaluated its performance by assessing its concordance with the approved SARS-CoV-2 real-time PCR assay. Tests were performed on 80 nasopharyngeal samples. The sensitivity and specificity of the M10 assay were 100%.The M10 assay effectively diagnosed SARS-CoV-2 infection, and it was comparable to the approved SARS-CoV-2 real-time PCR assay. It is a viable point-of-care test due to its short turnaround time.
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Background@#Self-sampling procedures to detect severe acute respiratory syndrome coronavirus 2 is important for patients who have difficulty visiting the hospital and may decrease the burden for health care workers (HCWs). The objective of this study was to evaluate the diagnostic performance, stability and usability of self-collected nasal and oral combo swabs and saliva specimens. @*Materials and Methods@#We conducted a case-control study with 50 patients with coronavirus disease 2019 (COVID-19) and 50 healthy volunteers from March, 2021 to June, 2021. We performed real-time reverse-transcription polymerase chain reaction to compare the diagnostic performance of self-collected specimens using positive percent agreements (PPAs). @*Results@#The PPAs between self-collected and HCW-collected specimens were 77.3 - 81.0% and 80.5 -86.7% for the combo swabs and saliva specimens, respectively. The PPAs increased to 88.9 - 89.2% and 81.2 - 82.1% with a cycle threshold value ≤30. @*Conclusion@#The diagnostic performance of self sampling was comparable to that of HCW sampling in patients with high viral loads and may thus assist in the early diagnosis of COVID-19.
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Background@#It is necessary to develop a roadmap for antimicrobial usage monitoring in order to perform monitoring of antimicrobial use at the national level properly. Therefore, this study aimed to develop a roadmap for establishing surveillance and monitoring of antimicrobial use in medical institutions at the national level. @*Materials and Methods@#A modified Delphi study was conducted, including 3 rounds of an online survey and a virtual meeting with 16 expert panels. The survey items were developed based on a literature review of the surveillance systems for antimicrobial use in 12 countries and interviews with experts. The questionnaire was designed to include both the surveillance and benchmarking systems. @*Results@#Regarding the scope of target institutions to be included in the surveillance system, medical institutions for sentinel surveillance had the highest proportion of agreement among the panels (75.0%, 9/12). For the benchmarking system, “tertiary- and secondarycare hospitals” were accepted as the scope of target institutions at the current moment.Furthermore, the National Health Insurance claims and prescription data of individual hospitals were considered appropriate data sources for the surveillance system. As for the measures to promote the participation of hospitals in the benchmarking system, “compensation through the establishment of antimicrobial management fees” and “set the participation in the program as a quality evaluation or accreditation index for hospital evaluation” were accepted. @*Conclusion@#This study provides a roadmap for establishing an antimicrobial use monitoring and benchmarking system for medical institutions at a national level in Korea.
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Currently, antimicrobial resistance (AMR) is a major threat to global public health. The antimicrobial stewardship program (ASP) has been proposed as an important approach to overcome this crisis. ASP supports the optimal use of antimicrobials, including appropriate dosing decisions, administration duration, and administration routes. In Korea, efforts are being made to overcome AMR using ASPs as a national policy. The current study aimed to develop core elements of ASP that could be introduced in domestic medical facilities. A Delphi survey was conducted twice to select the core elements through expert consensus.The core elements for implementing the ASP included (1) leadership commitment, (2) operating system, (3) action, (4) tracking, (5) reporting, and (6) education. To ensure these core elements are present at medical facilities, multiple departments must collaborate as teams for ASP operations. Establishing a reimbursement system and a workforce for ASPs are prerequisites for implementing ASPs. To ensure that ASP core elements are actively implemented in medical facilities, it is necessary to provide financial support for ASPs in medical facilities, nurture the healthcare workforce in performing ASPs, apply the core elements to healthcare accreditation, and provide incentives to medical facilities by quality evaluation criteria.
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Reducing antibiotics overuse is essential to minimize antibiotics related side effects and to prevent the emergence of multidrug-resistant bacteria. Procalcitonin (PCT) guided antibiotics therapy has been reported to be safe in patients with acute respiratory infections and sepsis, improving clinical outcomes as well as reducing the duration of antibiotics use.However, there is still no universal agreement on clinical guidelines in Korea for optimal PCT applications. Through this expert consensus meeting, clinical research findings in the PCT-guided antibiotics treatment interventions and real-world clinical applications were discussed. From the perspective of antibiotic stewardship, PCT application target groups, cut-offs, and testing cycles were discussed to reach a consensus on the PCT-guided antibiotics treatment algorithm for application in Korea. Combining clinical assessment for patients with an appropriate PCT-guided antibiotics treatment algorithm could improve the diagnosis and treatment of acute respiratory infections and sepsis. In addition, continuous education and regular feedback would improve the effectiveness of antibiotic stewardship.
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Identifying inappropriately prescribed antibiotics for infectious diseases by monitoring the quality of antibiotics use is essential for effective implementation of antibiotic stewardship. Qualitative assessment of the use of antibiotics has been conducted in some countries, including Korea, since the 2000s. The qualitative assessment generally involves an assessment of each component of the antibiotics prescription process, based on specific criteria. However, there is no standardized assessment method or cycle, and infectious diseases or antibiotics included in the assessments vary from country-to-country.According to the results reported in the United States, Europe, Australia, and Korea so far, approximately 20 - 55% of all antibiotics prescriptions are inappropriate. In this review, we describe the current progress in the quality assessment of the use of antibiotics on a global scale. Further, we highlight the future directions to improve antibiotic stewardship activities and the quality assessment of the use of antibiotics in Korea.
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As hospitals cater to elderly and vulnerable patients, a high mortality rate is expected if a coronavirus disease 2019 (COVID-19) outbreak occurs. Consequently, policies to prevent the spread of COVID-19 in hospital settings are essential. This study was conducted to investigate how effectively national and international guidelines provide recommendations for infection control issues in hospitals. After selecting important issues in infection control, we performed a systematic review and analysis of recommendations and guidelines for preventing COVID-19 transmission within medical institutions at national and international levels. We analyzed guidelines from the World Health Organization, Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control, and Korea Disease Control and Prevention Agency. Recent guidelines do not provide specific solutions to infection control issues. Therefore, efforts need to be made to devise consistent advice and guidelines for COVID-19 control.
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Recently, the number of patients with coronavirus disease 2019 (COVID-19) who have tested positive for severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), via the reverse transcription polymerase chain reaction (RT-PCR) test, after recovery has increased; this has caused a dilemma regarding the medical measures and policies. We evaluated the dynamics of viral load and anti-SARSCoV-2 antibodies in four patients with positive RT-PCR results after recovery. In all patients, the highest levels of immunoglobulin G (IgG) and IgM antibodies were reached after about a month of the onset of the initial symptoms. Then, the IgG titers plateaued, and the IgM titers decreased, regardless of RT-PCR results.The IgG and IgM levels did not increase after the post-negative positive RT-PCR results in any of the patients. Our results reinforced that the post-negative positive RT-PCR results may be due to the detection of RNA particles rather than reinfection in individuals who have recovered from COVID-19.
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BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality in East Asia. This study aimed to develop, for primary care providers, a prediction score using initial symptoms and basic laboratory blood tests to differentiate between SFTS and other endemic zoonoses in Korea.METHODS: Patients aged ≥ 18 years diagnosed with endemic zoonoses during a 3-year period (between January 2015 and December 2017) were retrospectively enrolled from 4 tertiary university hospitals. A prediction score was built based on multivariate logistic regression analyses.RESULTS: Of 84 patients, 35 with SFTS and 49 with other endemic zoonoses were enrolled. In multivariate logistic regression analysis, independent predictors of SFTS included neurologic symptoms (odds ratio [OR], 12.915; 95% confidence interval [CI], 2.173–76.747), diarrhea (OR, 10.306; 95% CI, 1.588–66.895), leukopenia (< 4,000/mm3) (OR, 19.400; 95% CI, 3.290–114.408), and normal C-reactive protein (< 0.5 mg/dL) (OR, 24.739; 95% CI, 1.812–337.742). We set up a prediction score by assigning one point to each of these four predictors. A score of ≥ 2 had 82.9% sensitivity (95% CI, 71.7%–87.5%) and 95.9% specificity (95% CI, 88.0%–99.2%). The area under the curve of the clinical prediction score was 0.950 (95% CI, 0.903–0.997).CONCLUSION: This study finding suggests a simple and useful scoring system to predict SFTS in patients with endemic zoonoses. We expect this strategic approach to facilitate early differentiation of SFTS from other endemic zoonoses, especially by primary care providers, and to improve the clinical outcomes.
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Background@#Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. @*Methods@#All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. @*Results@#The median age was 40 years (range, 20–73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5–7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). @*Conclusion@#The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.
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As the coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, there are growing concerns about patients' mental health. We investigated psychological problems in COVID-19 patients assessed with self-reported questionnaires including the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 scale, and Impact of Event ScaleRevised Korean version. Ten patients who recovered from COVID-19 pneumonia without complications underwent self-reported questionnaires about 1 month after discharge. Of them, 10% reported depression and posttraumatic stress disorder (PTSD) while 50% had depression during the treatment. Perceived stigma and history of psychiatric treatment affected PTSD symptom severity, consistent with previous emerging infectious diseases. Survivors also reported that they were concerned about infecting others and being discriminated and that they chose to avoid others after discharge. Further support and strategy to minimize their psychosocial difficulties after discharge should be considered.