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Abstract Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75–0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates.

Abstract Limited evidence exists regarding the link between coronavirus disease 2019 (COVID-19) and pneumothorax. Therefore, we aimed to evaluate the occurrence rate of pneumothorax in hospitalized patients with COVID-19 and compare the risk of pneumothorax between patients with COVID-19 and influenza. This retrospective cohort study used patient data from the National Health Insurance Service of South Korea. Patients diagnosed with COVID-19 (December 2019 to December 2021) and influenza (January 2019 to December 2021) who required hospitalization and respiratory support were included. We identified 46,460 patients with COVID-19 and 6,117 with influenza. The occurrence rate of pneumothorax was 0.74% in patients with COVID-19. In an inverse probability of treatment weighting matched cohort, the Cox proportional hazards regression model showed that COVID-19 was not associated with an increased risk of pneumothorax compared to influenza (hazard ratio, 1.22; 95% confidence interval, 0.75–1.99). However, the risk of pneumothorax associated with COVID-19 compared to influenza was significantly higher in patients without chronic lung disease than in those with (P for heterogeneity = 0.037). In conclusion, COVID-19, compared with influenza, is not associated with an increased risk of pneumothorax; however, it is associated with an increased risk in patients without chronic lung disease.

Abstract Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients’ blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients’ clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

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.

Abstract Galactomannan (GM) is a polysaccharide cell wall component released by Aspergillus spp., and an immunoenzymatic GM assay is used for the diagnosis of invasive pulmonary aspergillosis. We evaluated the cause of strong positivity for GM in patients with no typical signs of aspergillosis. Repeat assays were performed using different instruments and reagent lots, but there were no differences in results among the assays. Patients with strongly positive GM results were investigated. Medication histories revealed that 14 of 23 patients had been administered total parenteral nutrition solution from one manufacturer and 4 patients had been administered dextrose solution from a different manufacturer before being tested. The results of GM assays conducted on samples of dextrose solution and the glucose fraction of the total parenteral nutrition solution were strongly positive, confirming the causes of the false-positive reactions. We hypothesize that a trace amount of GM was introduced into the glucose-containing solutions because glucoamylase, which is necessary for the saccharification step of glucose synthesis, was derived from Aspergillus niger. To enhance patient care and prevent unnecessary antifungal prescriptions, healthcare providers and manufacturers of healthcare products need to be aware of the possibility of false-positive reactions for GM.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract Translational regulation in tissue environments during in vivo viral pathogenesis has rarely been studied due to the lack of translatomes from virus-infected tissues, although a series of translatome studies using in vitro cultured cells with viral infection have been reported. In this study, we exploited tissue-optimized ribosome profiling (Ribo-seq) and severe-COVID-19 model mice to establish the first temporal translation profiles of virus and host genes in the lungs during SARS-CoV-2 pathogenesis. Our datasets revealed not only previously unknown targets of translation regulation in infected tissues but also hitherto unreported molecular signatures that contribute to tissue pathology after SARS-CoV-2 infection. Specifically, we observed gradual increases in pseudoribosomal ribonucleoprotein (RNP) interactions that partially overlapped the trails of ribosomes, being likely involved in impeding translation elongation. Contemporaneously developed ribosome heterogeneity with predominantly dysregulated 5 S rRNP association supported the malfunction of elongating ribosomes. Analyses of canonical Ribo-seq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: ribosome stalling on codons within transmembrane domain-coding regions and compromised translation of immunity- and metabolism-related genes with upregulated transcription. Our findings collectively demonstrate that the abrogation of translation integrity may be one of the most critical factors contributing to pathogenesis after SARS-CoV-2 infection of tissues.

Abstract In this work, via engineering the conformation of cobalt active center in cobalt phthalocyanine molecular catalyst, the catalytic efficiency of electrochemical carbon monoxide reduction to methanol can be dramatically tuned. Based on a collection of experimental investigations and density functional theory calculations, it reveals that the electron rearrangement of the Co 3d orbitals of cobalt phthalocyanine from the low-spin state (S = 1/2) to the high-spin state (S = 3/2), induced by molecular conformation change, is responsible for the greatly enhanced CO reduction reaction performance. Operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy measurements disclose accelerated hydrogenation of CORR intermediates, and kinetic isotope effect validates expedited proton-feeding rate over cobalt phthalocyanine with high-spin state. Further natural population analysis and density functional theory calculations demonstrate that the high spin Co2+ can enhance the electron backdonation via the d xz /d yz −2π* bond and weaken the C-O bonding in *CO, promoting hydrogenation of CORR intermediates.

Abstract Background We aimed to develop a roadmap for conducting regular, sustainable, and strategic qualitative assessments of antibiotic use in medical institutions within the Republic of Korea. Methods A literature review on the current state of qualitative antibiotic assessments was conducted, followed by one open round to collect ideas, two scoring rounds to establish consensus, and one panel meeting between them. The expert panel comprised 20 experts in infectious disease or antibiotic stewardship. Results The response rate for all three surveys was 95% (19/20), while the panel meeting attendance rate was 90% (18/20). The following long-term goals were defined to assess the annual use of antibacterial and antifungal agents in all medical institutions, including clinics. The panel agreed that random sampling of antibiotic prescriptions was the most suitable method of selecting antibiotics for qualitative assessment, with the additional possibility of evaluating specific antibiotics or infectious diseases that warrant closer evaluation for promoting appropriate antibiotic use. The plan for utilization of results from evaluation involves providing feedback while maintaining anonymity and disclosure. It includes a quantitative assessment of antibiotic prescriptions and resistance rates to compare against institutional benchmarks. Furthermore, it was agreed to link the evaluation findings to the national antibiotic stewardship programme, enabling policy and institutional approaches to address frequently misused items, identified during the evaluation. Conclusion This study provides a framework for establishing a qualitative assessment of antimicrobial use for medical institutions at a national level in the Republic of Korea.

ABSTRACTIn 2015, Staphylococcus argenteus and Staphylococcus schweitzeri were proposed as new species, distinct from Staphylococcus aureus and collectively referred to as the S. aureus complex. However, no clinical reports of these new species exist in Korea. Upon the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for all bloodstream isolates since September 2022, S. argenteus was identified in one patient. Therefore, we aimed to search for new species among the archives of the S. aureus bacteremia cohort and describe their clinical and microbiological characteristics. Among the 691 archived S. aureus isolates between 2012 and 2018, one was identified as S. argenteus via MALDI-TOF MS. Both S. argenteus isolates (one in 2022) were obtained from patients with extensive pneumonia accompanied by bacteremia and both cases had fatal outcomes. They harbored multiple virulence genes (clfA, clfB, fnbpA, sdrC, sdrD, sdrE, bbp, cna, see, seg, sei, blaZ, fnbpB, and map) but did not harbor mecA and pvl. No matched sequence type (ST) was found in either isolate, and both S. argenteus isolates were closely related to ST1594, ST1593, ST1793, and ST1303, which belonged to S. argenteus. S. argenteus accounted for

Abstract Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P

Summary: Background: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus’s impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. Methods: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. Findings: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor–ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFβ signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. Interpretation: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFβ signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501).

We report a case of occupational monkeypox virus infection from a needlestick injury in a healthcare worker in South Korea and review similar reports in the literature during 2022. Postexposure prophylactic treatment with a third-generation smallpox vaccine and antiviral agent tecovirimat inhibited local virus spread and alleviated lesion pain.

ABSTRACT: Objectives: The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. Methods: We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. Results: During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020–$416,094,679) in socioeconomic loss. Conclusions: A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

ABSTRACT: Objectives: Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteraemia occur within a few days after the onset of bacteraemia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteraemia. Methods: Clinical information on all patients with CRAB bacteraemia in 10 hospitals during a 1-year period was collected. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively. Results: In total, 212 CRAB bacteraemia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score was significantly higher in patients with EM than those with LM. Although urinary tract infection as the site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM. Conclusion: Our results suggest that a large proportion of CRAB bacteraemia with high severity progresses to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM.

Abstract A reduction in the unnecessary use of antibiotic prophylaxis can prevent antibiotic resistance and adverse drug events. We aimed to evaluate the effects of implementing clinical pathways (CPs) on adherence to a systematic and appropriate duration of antibiotic prophylaxis. We identified 61 eligible CPs and a total of 44,062 patients who underwent elective surgeries associated with CPs. The Poisson mixed model with an interrupted time-series analysis frame was applied to the patient-level data. This enabled a comparison of the adherence rate before and after CP implementation. Furthermore, we examined the effect of application or completion of CP on the adherence rate after implementation. Adherence to the antibiotic prophylaxis guideline substantially increased (incident rate ratio [IRR] 8.05; 95 confidence interval [CI] 2.64–24.55), compared with that before implementation. Following the implementation into the electronic entry system, we observed an improved adherence not only in CP completion but also in attempted CP execution (IRR of the executed but not completed cases 1.54; 95% CI 1.17–2.04; IRR of the executed and competed cases, 1.94; 95% CI 1.4–2.69). The implementation of CP into the electronic prescribing system was associated with a significant increase in the appropriate use of antibiotic prophylaxis among patients who underwent elective surgeries. The results suggest that a computer-assisted CP system for electronic health records could improve antibiotic adherence without significant expense.

Objective The aim of this study was to compare the effects of three kinds of organic acid (OA) products on the growth performance, intestinal characteristics and morphology, and cecal microflora in broilers fed a corn–soybean meal meal diet. Methods A total of 420 one-day-old male Cobb 500 broilers with an average initial body weight of 49.11±1.02 g were used in this 42-day experiment. Birds were randomly allotted to one of five treatments (7 replicates with 12 birds per replicate). Treatments consisted of negative control (NC), basal diet; positive control (PC), basal diet+100 mg/kg of Aviramycin; OA1, basal diet+500 mg/kg of OA product 1; OA2, basal diet+1,000 mg/kg of OA product 2; and OA3, basal diet+1,200 mg/kg of OA product 3. Results The results indicated that OA product addition had no effect on growth performance parameters, such as body weight gain, feed intake, and feed conversion ratio, from days 1 to 14, 15 to 28, and 0 to 42, or on the pH values of the intestine, intestinal weight, or intestinal weight to body weight ratio. The intestinal morphology in terms of villus height and crypt depth were affected by dietary supplementation of OA products, respectively. Furthermore, dietary addition of OAs had positive influences on the maintenance of the cecal microflora based on the results of 16S rRNA analysis. Conclusion Dietary inclusion of three kinds of OA products all benefit broilers, but the mode of action may be different. This study provides a basis for the application of OA products used in the poultry industry.

ABSTRACTIn this study, red and yellow varieties of djulis (Chenopodium formosanum Koidz) were cultivated in spring and autumn, and the effects of calcium carbonate treatment on their growth traits, antioxidant capacity, and grain maturation were examined. This study showed that calcium carbonate treatment increased the plant height and stem thickness in the red variety of djulis. The treatment also significantly increases the yield components of the red variety of djulis, such as spike length and thousand-grain weight. Treating the red variety of djulis with calcium carbonate in spring significantly increased the antioxidant enzyme activity such as superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR) activities. Interestingly, results indicated that calcium carbonate treatment could promote the early maturation of the mid-late-maturing red variety of djulis and delay the maturation of the early-maturing yellow variety. Hence this experiment concludes that the exogenous calcium treatment in djulis can regulate grain maturation and promote growth, yield, and antioxidant enzyme activity; however, the growing season and the varietal effects play a vital role in determining the overall productivity of the djulis crop.

Abstract We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309–2483 and 339–644, with 485–920 and 133–253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723–122,533,585 and $15,241,883–28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648–3127 patients, resulted in 618–1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606–151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.

Objectives: We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS. Methods: We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues. Results: During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13–11.99, P = 0.030). Conclusions: We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0–85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS.

Background: There have been occasional reports on varicella infection among healthcare workers (HCWs) despite varicella-zoster virus (VZV) seropositivity. We compared the levels of humoral and cellular immunity to VZV in seropositive HCWs who had acquired immunity by natural infection or vaccination. Methods: Seropositive healthy HCWs with an apparent history of varicella or VZV vaccination once or twice were recruited. Their samples were assessed for anti-VZV IgG levels, the relative avidity index (RAI), and the frequencies of VZV-specific cytokine-producing or polyfunctional CD4+ or CD8+ T cells. Results: A total of 75 seropositive HCWs (29 with a history of varicella, 25 vaccinated once, and 21 vaccinated twice) were assessed for humoral immunity. Cellular responses could be analyzed in 59 (28, 21, and 10 in the respective groups). The anti-VZV IgG level, RAI, and memory CD4+ T cell responses were significantly higher in the past infection group than in the vaccinated once group. The RAI levels were significantly higher in the past infection group than in the vaccinated twice group. Conclusion: Seropositive HCWs without a varicella history, especially those who received the vaccine only once, had significantly lower levels of immune responses to VZV. Such HCWs might need to comply with airborne precautions.

Abstract 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.

ABSTRACT: Objectives: Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea. Methods: The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated. Results: The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699). Conclusion: This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

BackgroundLittle is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19.MethodsWe prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively.ResultsAnti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19.ConclusionsSevere breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Abstract Background Given the increasing incidence of Clostridioides difficile infections in Korea, there has been an increase in inappropriate testing for C. difficile, which has rendered overdiagnosis of asymptomatic colonisers common. We aimed to investigate the appropriateness of C. difficile testing and the related factors. Methods We retrospectively reviewed the medical records of patients who were admitted to a 1300-bed tertiary-care teaching hospital in Korea and were tested for C. difficile infection from September 2019 to November 2019. We performed logistic regression analysis to investigate factors related to inappropriate testing. Further, a survey was conducted on physicians to assess the knowledge and ordering patterns of C. difficile testing. Results We included 715 tests from 520 patients in the analysis. Testing was classified as hospital-onset and community-onset and subclassified as appropriate and inappropriate following an algorithmic method. Among the 715 tests, 576 (80.6%) and 139 (19.6%) tests were classified as hospital-onset and community-onset, respectively. Among the hospital-onset tests, 297 (52%) were considered inappropriate. The risk of inappropriate testing increased when C. difficile tests were conducted in the emergency room (OR 24.96; 95% CI 3.12–199.98) but decreased in intensive care units (OR 0.36, 95% CI 0.19–0.67). The survey was conducted on 61 physicians. Internal medicine physicians had significantly higher scores than non-internal medicine physicians (7.1 vs. 5.7, p = 0.001). The most frequently ordered combination of tests was toxin + glutamate dehydrogenase (47.5%), which was consistent with the ordered tests. Conclusion Almost half of the C. difficile tests were performed inappropriately. The patient being located in the emergency room and intensive care unit increased and decreased the risk of inappropriate testing, respectively. In a questionnaire survey, we showed that internal medicine physicians were more knowledgeable about C. difficile testing than non-internal medicine physicians. There is a need to implement the diagnostic stewardship for C. difficile, especially through educational interventions for emergency room and non-internal medicine physicians.

Abstract This study aimed to evaluate the differences in clinical characteristics and impact of carbapenem resistance (CR) on outcomes between Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) bacteraemia. We prospectively identified all patients with Ab and Pa bacteraemia in 10 hospitals over 1 year. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrent bacteraemia within 30 days. We included 304 Ab and 241 Pa bacteraemia cases. CR was detected in 216 patients (71%) with Ab bacteraemia and 55 patients (23%) with Pa bacteraemia. Treatment failure was significantly higher in CR-Ab than in CR-Pa (60.6% vs. 34.5%, P = 0.001). In Ab, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. In Pa, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in Ab for treatment failure in both groups, but not in Pa bacteraemia. We demonstrated significant differences in clinical characteristics and impact of CR on clinical outcomes between Ab and Pa bacteraemia, suggesting that different treatment approaches may be needed.

Abstract Background Although non-teaching community hospitals form the majority of healthcare providers in South Korea, there is limited data on antibiotic usage in them. To evaluate the pattern of antibiotic usage and its appropriateness in hospitals with

Abstract Objective: To evaluate antibiotic prescribing behavior (APB) among physicians with various specialties in five Asian countries. Design: Survey of antibiotics prescribing behavior in three stages (initial, on-treatment, and de-escalation stages). Methods: Participants included internists, infectious diseases (ID) specialists, hematologists, intensivists, and surgeons. Participants’ characteristics, patterns of APB, and perceptions of antimicrobial stewardship were collected. A multivariate analysis was conducted to evaluate factors associated with appropriate APB. Results: There were 367 participants. The survey response rate was 82.5% (367/445). For the initial stage, different specialties had different choices for empiric treatment. For the on-treatment stage, if the patient does not respond to empiric treatment, most respondents will step up to broader-spectrum antibiotics (273/367: 74.39%). For the de-escalation stage, the rate of de-escalation was 10%–60% depending on the specialty. Most respondents would de-escalate antibiotics based on guidelines (250/367: 68.12%). De-escalation was mostly reported by ID specialists (66/106: 62.26%). Respondents who reported that they performed laboratory investigations prior to empirical antibiotic prescriptions (aOR = 2.83) were associated with appropriate use, while respondents who reported ID consultation were associated with appropriate antibiotic management for infections not responding to empiric treatment (aOR = 40.87); adherence with national guidelines (aOR = 2.57) was associated with reported successful carbapenem de-escalation. Conclusion: This study highlights the variation in practices and gaps in appropriate APB on three stages of antibiotic prescription among different specialties. Education on appropriate investigation, partnership with ID specialist, and availability and adherence with national guidelines are critical to help guide appropriate APB among different specialties.

Abstract Objectives Few studies have investigated the contamination of personal protective equipment (PPE) during the management of patients with severe-to-critical coronavirus disease (COVID-19). This study aimed to determine the necessity of coveralls and foot covers for body protection during the management of COVID-19 patients. Methods PPE samples were collected from the coveralls of physicians exiting a room after the management of a patient with severe-to-critical COVID-19 within 14 days after the patient’s symptom onset. The surface of coveralls was categorized into coverall-only parts (frontal surface of the head, anterior neck, dorsal surface of the foot cover, and back and hip) and gown-covered parts (the anterior side of the forearm and the abdomen). Sampling of the high-contact surfaces in the patient’s environment was performed. We attempted to identify significant differences in contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between the coverall-only and gown-covered parts. Results A total of 105 swabs from PPEs and 28 swabs from patient rooms were collected. Of the PPE swabs, only three (2.8%) swabs from the gown-covered parts were contaminated with SARS-CoV-2. However, 23 of the 28 sites (82.1%) from patient rooms were contaminated. There was a significant difference in the contamination of PPE between the coverall-only and gown-covered parts (0.0 vs 10.0%, p = 0.022). Conclusions Coverall contamination rarely occurred while managing severe-to-critical COVID-19 patients housed in negative pressure rooms in the early stages of the illness. Long-sleeved gowns may be used in the management of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a global health concern since 2019. The viral spike protein infects the host by binding to angiotensin-converting enzyme 2 (ACE2) expressed on the cell surface, which is then processed by type II transmembrane serine protease. However, ACE2 does not react to SARS-CoV-2 in inbred wild-type mice, which poses a challenge for preclinical research with animal models, necessitating a human ACE2 (hACE2)-expressing transgenic mouse model. Cytokeratin 18 (K18) promoter-derived hACE2 transgenic mice [B6.Cg-Tg(K18-ACE2)2Prlmn/J] are widely used for research on SARS-CoV-1, MERS-CoV, and SARS-CoV-2. However, SARS-CoV-2 infection is lethal at ≥105 PFU and SARS-CoV-2 target cells are limited to type-1 alveolar pneumocytes in K18-hACE2 mice, making this model incompatible with infections in the human lung. Hence, we developed lung-specific SARS-CoV-2 infection mouse models with surfactant protein B (SFTPB) and secretoglobin family 1a member 1 (Scgb1a1) promoters. After inoculation of 105 PFU of SARS-CoV-2 to the K18-hACE2, SFTPB-hACE2, and SCGB1A1-hACE2 models, the peak viral titer was detected at 2 days post-infection and then gradually decreased. In K18-hACE2 mice, the body temperature decreased by approximately 10°C, body weight decreased by over 20%, and the survival rate was reduced. However, SFTPB-hACE2 and SCGB1A1-hACE2 mice showed minimal clinical signs after infection. The virus targeted type I pneumocytes in K18-hACE2 mice; type II pneumocytes in SFTPB-hACE2 mice; and club, goblet, and ciliated cells in SCGB1A1-hACE2 mice. A time-dependent increase in severe lung lesions was detected in K18-hACE2 mice, whereas mild lesions developed in SFTPB-hACE2 and SCGB1A1-hACE2 mice. Spleen, small intestine, and brain lesions developed in K18-hACE2 mice but not in SFTPB-hACE2 and SCGB1A1-hACE2 mice. These newly developed SFTPB-hACE2 and SCGB1A1-hACE2 mice should prove useful to expand research on hACE2-mediated respiratory viruses.

Background: Although small- and medium-sized hospitals comprise most healthcare providers in South Korea, data on antibiotic usage is limited in these facilities. We evaluated the pattern of antibiotic usage and its appropriateness in hospitals with

Summary: COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8+ T cells using MHC class I (MHC-I) multimers and correlations between early differentiation and the durability of CD8+ T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer+ cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%–65.6% (23.0% on average) of the peak. MHC-I multimer+ cells dominantly exhibit phenotypes of activated effector cells 1–2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (TSCM) cells. Importantly, the frequency of TSCM cells 1–2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8+ T cells, indicating that early generation of TSCM cells determines the longevity of vaccine-induced memory CD8+ T cell responses.

ABSTRACT To optimize antibiotic use, the US CDC has outlined core elements of antimicrobial stewardship programs (ASP). However, they are difficult to implement in limited-resource settings. We report on the successful implementation of a series of ASP with insufficient number of infectious diseases specialists. We retrospectively collected data regarding antibiotic administration and culture results of all patients admitted to a tertiary care teaching hospital, Seoul National University Bundang Hospital (SNUBH), from January 2010 to December 2019. Trends of antibiotic use and antibiotic resistance rates were compared with those from Korean national data. Trend analyses were performed using nonparametric, two-sided, correlated seasonal Mann–Kendall tests. Total antibiotic agent usage has significantly decreased with ASP implementation at SNUBH since 2010. National claim data from tertiary care hospitals have revealed an increase in the use of all broad-spectrum antibiotics except for third-generation cephalosporins (3GC). In contrast, at SNUBH, glycopeptide and fluoroquinolone use gradually decreased, and 3GC and carbapenem use did not significantly change. Furthermore, the rate of colonization with methicillin-resistant Staphylococcus aureus showed a consistently decreasing trend, while that with 3GC- and fluoroquinolone-resistant Escherichia coli significantly increased. Unlike the national rate, the rate of colonization with antibiotic resistant-Klebsiella pneumoniae did not increase and that of 3GC- and fluoroquinolone-resistant Pseudomonas aeruginosa significantly decreased. Stepwise implementation of core ASP elements was effective in reducing antibiotic use despite a lack of sufficient manpower. Long-term multidisciplinary teamwork is necessary for successful and sustainable ASP implementation. IMPORTANCE Antimicrobial stewardship programs aimed to optimize antibiotic use are difficult to implement in limited-resource settings. Our study indicates that stepwise implementation of core antimicrobial stewardship program elements was effective in reducing antibiotic use in a tertiary care hospital despite the lack of sufficient manpower.

Purpose: A novel once-daily divalproex-extended release (ER) dose formulation has been developed; this formulation prolongs the therapeutic serum levels of the drug, compared with the twice-daily conventional divalproex-delayed release (DR) formulation. This study aimed to systematically examine and compare the efficacy, safety, and retention rates of the ER divalproex (VPA-ER) and conventional DR divalproex (VPA-DR) formulations.Methods: Randomized control trials (RCTs) reporting the efficacy, adverse events (AEs), and medication compliance of ER and DR divalproex were searched in online databases, including PubMed, Embase, and Cochrane Library databases, by searching MeSH words and term words. Observational studies with potential biases were excluded. The meta-analysis was performed using Stata 16.0 software.Findings: Thirteen RCTs, involving 1,028 participants, were included in this meta-analysis. Efficacy, AEs, and drug retention rates were the main study outcomes. According to our study, VPA-ER presented clinically significant benefits compared with the placebo in the population with bipolar disorder (BD) (39.5% versus 27.2%, p < 0.001). A similar efficacy of VPA-ER and VPA-DR in controlling seizures was observed in epilepsy patients (87.4% versus 86.5%, p = 0.769). A significantly lower incidence of AEs was reported in the VPA-ER group than in the placebo group (26.8% versus 34.8%, p = 0.003). By contrast, there was no evidence of difference in safety between VPA-ER and VPA-DR (29.4% versus 30.5%, p = 0.750). In addition, the drug retention rate was significantly lower in the VPA-ER group than in the placebo group (76.0% versus 82.7%, p = 0.020), especially in migraine patients (p = 0.022) and in patients who were treated for fewer than 4 weeks (p = 0.018).Implications: The efficacy of VPA-ER was significantly superior to that of the placebo treatment, which provided efficacy similar to that of conventional VPA-DR. VPA-ER is well tolerated with a low rate of AEs compared to the placebo. In addition, the acceptable medicine compliance of VPA-ER was conducive to the long-term maintenance treatment of chronic diseases. Although we analyzed open labels and crossover design RCTs, large-scale multicenter studies on the efficacy and medicine compliance of new ER formulations with less AEs are required to validate our conclusion.

ABSTRACT Here, we aimed to investigate the diagnostic value of a serological assay using the nucleocapsid protein developed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection and evaluated its performance using three commercial enzyme-linked immunosorbent assays (ELISAs), namely, Standard E 2019 novel coronavirus disease (COVID-19) total antibody (Ab) ELISA (SD Biosensor), and EDI novel coronavirus COVID-19 IgG and IgM ELISA. A recombinant nucleocapsid protein (rNP) was expressed from plants and Escherichia coli for the detection of serum total Ab. We prospectively collected 141 serum samples from 32 patients with reverse transcription-PCR (RT-PCR)-confirmed COVID-19 and determined the sensitivity and dynamics of their total Ab response. Specificity was evaluated using 158 prepandemic samples. To validate the assays, we evaluated the performance using two different cutoff values. The sensitivity and specificity for each assay were as follows: 92.91% and 94.30% (plant-rNP), 83.69% and 98.73% (SD Biosensor), 75.89% and 98.10% (E. coli-rNP), 76.47% and 100% (EDI-IgG), and 80.39% and 80% (EDI-IgM). The plant-based rNP showed the highest sensitivity and area under the receiver operating characteristic (ROC) curve (0.980) among all the assays (P 80% and 100% for EDI-IgM and EDI-IgG ELISA, respectively. Seroconversion occurred earlier with rNP plant-based ELISA (5 days PSO) compared with E. coli-based (7 days PSO) and SD Biosensor (8 days PSO) ELISA. We determined that rNP produced in plants enables the robust detection of SARS-CoV-2 total Abs. The assay can be used for serosurvey and complementary diagnosis of COVID-19. IMPORTANCE At present, the principal diagnostic methods for COVID-19 comprise the identification of viral nucleic acid by genetic approaches, including PCR-based techniques or next-generation sequencing. However, there is an urgent need for validated serological assays which are crucial for the understanding of immune responses against SARS-CoV-2. In this study, a highly sensitive and specific serological antibody assay was developed for the detection of SARS-CoV-2 with an overall accuracy of 93.56% using a recombinant nucleoprotein expressed from plants.