Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice.

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.

Relationship between the appropriateness of antibiotic treatment and clinical outcomes/medical costs of patients with community-acquired acute pyelonephritis: a multicenter prospective cohort study.

BACKGROUND: Inappropriate use of antibiotics not only increases antibiotic resistance as collateral damage but also increases clinical failure rates and medical costs. The purpose of this study was to determine the relationship between the appropriateness of antibiotic prescription and outcomes of community-acquired acute pyelonephritis (CA-APN). METHODS: A multicenter prospective cohort study was conducted at eight hospitals in Korea between September 2017 and August 2018. All hospitalized patients aged ≥ 19 years who were diagnosed with CA-APN on admission were recruited. The appropriateness of empirical and definitive antibiotics, as well as the appropriateness of antibiotic treatment duration and route of administration, was evaluated in accordance with the guideline and expert opinions. Clinical outcomes and medical costs were compared between patients who were administered antibiotics 'appropriately' and 'inappropriately.' RESULTS: A total of 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of them, 10 (2.5%) and 18 (5.7%) were administered 'inappropriately' empirical and definitive antibiotics, respectively. Of the 119 patients whose use of both empirical and definitive antibiotics was classified as 'optimal,' 57 (47.9%) received antibiotics over a longer duration than that recommended; 67 (56.3%) did not change to oral antibiotics on day 7 of hospitalization, even after stabilization of the clinical symptoms. Patients who were administered empirical antibiotics 'appropriately' had shorter hospitalization days (8 vs. 10 days, P = 0.001) and lower medical costs (2381.9 vs. 3235.9 USD, P = 0.002) than those who were administered them 'inappropriately.' Similar findings were observed for patients administered both empirical and definitive antibiotics 'appropriately' and those administered either empirical or definitive antibiotics 'inappropriately'. CONCLUSIONS: Appropriate use of antibiotics leads to better outcomes, including reduced hospitalization duration and medical costs.

Maternal and Neonatal Outcomes in Pregnant Women With Coronavirus Disease 2019 in Korea.

BACKGROUND: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. METHODS: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. RESULTS: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. CONCLUSION: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

Response System for and Epidemiological Features of COVID-19 in Gyeongsangnam-do Province in South Korea.

BACKGROUND: The South Korean government has been combating the coronavirus disease 2019 (COVID-19) outbreak using public information and extensive viral screening. We describe the application of the Korean response system in Gyeongsangnam-do province and outline the epidemiological features of COVID-19 in the cohort. METHODS: A Rapid Response Team tracked the patients' activities and identified close contacts. A Patient Management Team made decisions regarding the severity of illness, hospital allocation depending on severity, and time of discharge. A national medical center with 155 beds and 4 university-affiliated hospitals with 48 negative-pressure isolation rooms were dedicated for patients with COVID-19. RESULTS: As of 15 April, 17 400 residents were tested, of whom 111 were confirmed positive cases. Of the 111 patients, 78 were cured and discharged, 2 recovered after mechanical ventilation, and none died. One healthcare worker at the national center tested positive for SARS-CoV-2. All 412 staff members at the center were tested, but there were no additional infections. Cough (30.0%) was the most common initial symptom, whereas anosmia and ageusia were the first symptoms in 14.7% and 15.7% of the patients, respectively. Overall, 25 patients (22.5%) reported having no symptoms at admission and 7 (6.3%) remained asymptomatic at discharge. CONCLUSIONS: A response system that enabled the early detection of COVID-19 cases, including asymptomatic and presymptomatic cases, and timely quarantine of these patients and their contacts, along with efficient allocation of medical resources, was the key to curbing the COVID-19 outbreak in Gyeongsangnam-do Province.

Comparison of the clinical characteristics of community-acquired acute pyelonephritis between male and female patients.

BACKGROUND: Community-acquired acute pyelonephritis (CA-APN) is relatively rare in men. This study aimed to compare the clinical characteristics of CA-APN between male and female patients. METHODS: We prospectively collected the clinical and microbiological data of hospitalized CA-APN patients aged ≥19 years in South Korea from March 2010 to February 2011 in 11 hospitals and from September 2017 to August 2018 in 8 hospitals. Only the first episodes of APN of each patient during the study period were included. RESULTS: From 2010 to 2011, 573 patients from 11 hospitals were recruited, and from 2017 to 2018, 340 patients were recruited from 8 hospitals. Among them, 5.9% (54/913) were male. Male patients were older (66.0 ± 15.2 vs. 55.3 ± 19.0 years, P < 0.001), had a higher Charlson comorbidity index (1.3 ± 1.5 vs. 0.7 ± 1.2, P = 0.027), and had a higher proportion of structural problems in the urinary tract (40.7% vs. 6.1%, P < 0.001) than female patients. Moreover, the total duration of antibiotic treatment was longer (21.8 ± 17.8 d vs. 17.3 ± 9.4 d, P = 0.001) and the proportion of carbapenem usage was higher (24.1% vs. 9.5%, P = 0.001) in men than in women. Male patients were hospitalized for longer durations than female patients (median, 10 d vs. 7 d, P < 0.001). CONCLUSIONS: Male CA-APN patients were older and had more comorbidities than female CA-APN patients. In addition, male patients received antibiotic treatment for a longer duration than female patients.

Clinical Features of Adult COVID-19 Patients without Risk Factors before and after the Nationwide SARS-CoV-2 B.1.617.2 (Delta)-variant Outbreak in Korea: Experience from Gyeongsangnam-do.

BACKGROUND: Data on severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) delta variant virulence are insufficient. We retrospectively compared the clinical features of adult coronavirus disease 2019 (COVID-19) patients without risk factors for severe COVID-19 who entered residential treatment centers (RTCs) before and after the delta variant outbreak. METHODS: We collected medical information from two RTCs in South Korea. On the basis of nationwide delta variant surveillance, we divided the patients into two groups: 1) the delta-minor group (diagnosed from December 2020-June 2021, detection rate < 10%) and 2) the delta-dominant group (diagnosed during August 2021, detection rate > 90%). After propensity-score matching, the incidences of pneumonia, hospital transfer and need for supplemental oxygen were compared between the groups. In addition, risk factors for hospital transfer were analysed. RESULTS: A total of 1,915 patients were included. The incidence of pneumonia (14.6% vs. 9.2%, P = 0.009), all-cause hospital transfer (10.4% vs. 6.3%, P = 0.020) and COVID-19-related hospital transfer (7.5% vs. 4.8%, P = 0.081) were higher in the delta-dominant group than those in the delta-minor group. In the multivariate analysis, the delta-dominant group was an independent risk factor for all-cause (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.16-3.13; P = 0.011) and COVID-19-related hospital transfer (aOR, 1.86; 95% CI, 1.04-3.32; P = 0.036). CONCLUSION: Hospitalization rates were increased in the adult COVID-19 patients during the delta variant nationwide outbreak. Our results showed that the delta variant may be more virulent than previous lineages.

Clinical and Molecular Characteristics of qacA- and qacB-Positive Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections.

The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA and qacB chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA- and qacB-positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. A total of 246 MRSA BSI isolates were included; 71 (28.9%) isolates carried qacA/B The annual frequency of qacA- and qacB-positive MRSA bacteremia did not change significantly over the study period. Patients infected with qacA- and qacB-positive MRSA had common risk factors for health care-associated infections, including prior antibiotic use, central venous catheterization in situ, intensive care unit-acquired bacteremia, and nosocomial infection. The qacA- and qacB-positive isolates were also associated with an increasing chlorhexidine MIC and resistance to non-ß-lactam antibiotics. The qacA- and qacB-positive isolates were more likely to belong to sequence type 5 (ST5), which is a common health care-associated MRSA strain in South Korea. In multivariable analyses, qacA- and qacB-positive MRSA isolates were found to be associated with agr dysfunction (adjusted odds ratio [aOR], 6.45; 95% confidence interval [CI], 2.59 to 16.10), ST5 MRSA strain (aOR, 4.96; 95% CI, 1.85 to 13.26), nosocomial infection (aOR, 4.88; 95% CI, 2.20 to 10.83), and antibiotic use within the previous 3 months (aOR, 2.59; 95% CI, 1.20 to 5.59). These findings suggest that the microbiological features of qacA and qacB carriage provide a selective advantage for specific MRSA strains in hospital environments.

Distinct molecular evolution of influenza H3N2 strains in the 2016/17 season and its implications for vaccine effectiveness.

Influenza virus is a respiratory pathogen that causes seasonal epidemics by resulting in a considerable number of influenza-like illness (ILI) patients. During the 2016/17 season, ILI rates increased unusually earlier and higher than previous seasons in Korea, and most viral isolates were subtyped as H3N2 strains. Notably, the hemagglutinin (HA) of most Korean H3N2 strains retained newly introduced lysine signatures in HA antigenic sites A and D, compared with that of clade 3C.2a vaccine virus, which affected antigenic distances to the standard vaccine antisera in a hemagglutination inhibition assay. The neuraminidase (NA) of Korean H3N2 strains also harbored amino acid mutations. However, neither consistent amino acid mutations nor common phylogenetic clustering patterns were observed. These suggest that Korean H3N2 strains of the 2016/17 season might be distantly related with the vaccine virus both in genotypic and phenotypic classifications, which would adversely affect vaccine effectiveness.

Clinical courses and outcomes of hospitalized adult patients with seasonal influenza in Korea, 2011-2012: Hospital-based Influenza Morbidity & Mortality (HIMM) surveillance.

Influenza is an acute respiratory illness, which can be accompanied by complications such as pneumonia. This study was conducted to survey the clinical courses and outcomes of hospitalized adult patients with laboratory-confirmed seasonal influenza. A prospective case-control study was performed in adult influenza patients who were admitted to hospitals participating in the Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system in Korea from October 2011 to May 2012. Cases with complicated influenza were compared to those without complications. A total of 123 (5.6%) patients among 2184 laboratory-confirmed adult influenza patients were hospitalized during the 2011-2012 influenza epidemic season. Forty (32.5%) experienced 50 complication episodes. Age older than 60 years (P < 0.01), male sex (P = 0.04), diabetes (P < 0.01), chronic cardiovascular disease (P < 0.01) and neuromuscular disease (P = 0.02) were significantly related to development of complications in univariate analysis. Multivariate logistic regression analysis revealed that diabetes (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.15-11.51, P = 0.02) was an independent risk factor for complicated seasonal influenza. C-reactive protein (CRP) was discriminative between complicated and uncomplicated influenza (cutoff value 13 mg/L, sensitivity 70%, specificity 74%). Complicated patients received antibiotics more frequently (P < 0.01) with longer hospital stays (P = 0.01). In conclusion, diabetic patients are at great risk for complicated influenza, and CRP would be useful to predicting complication. Therefore, early interventions such as antiviral therapy should be considered for high risk patients with diabetes, especially those with increased serum CRP level.

Pulmonary toxocariasis mimicking invasive aspergillosis in a patient with ulcerative colitis.

A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.

Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model.

While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.

Persistent Pneumonic Consolidations due to Secondary Organizing Pneumonia in a Patient Recovering from COVID-19 Pneumonia: A Case Report and Literature Review.

In patients recovering from coronavirus disease 2019 (COVID-19) pneumonia, respiratory symptoms and radiographic pneumonic infiltrate occasionally persist for many weeks even after viral clearance; thereby, making it difficult to decide on an appropriate treatment. Here, we describe a 46-year-old woman with COVID-19 pneumonia who had persistent radiographic pneumonic infiltration and respiratory symptoms for almost 4 weeks after illness onset, despite viral clearance, and was subsequently diagnosed with secondary organizing pneumonia (SOP) using video-assisted thoracoscopic (VATS) wedge lung biopsy. Intravenous methylprednisolone was administered at an initial dose of 50 mg/day (1 mg/kg) for 7 days and was tapered to a dose of prednisolone 30 mg/day following improvement in the patient's respiratory symptoms and chest radiographic findings. The patient was discharged from the hospital 14 days after the initiation of corticosteroid treatment. The dose of prednisolone was tapered monthly to 20, 15, 10, and 5 mg/day, respectively, at the outpatient clinic for a total duration of 6 months; nearly resolved pneumonic infiltrations were observed in a follow-up computed tomography scan approximately 2 months after she was admitted. To the best of our knowledge, this is the first case report of a COVID-19 associated SOP that was pathologically confirmed through VATS wedge lung biopsy in Korea. SOP should be considered in the differential diagnosis of patients with COVID-19 pneumonia with persistent respiratory symptoms and radiographic pneumonic infiltrations during the recovery phase to avoid the redundant use of antimicrobial or antiviral agents. Furthermore, histological confirmation is essential for the definitive diagnosis of SOP to avoid unnecessarily prolonged corticosteroid treatment.

Fatal Primary Amebic Meningoencephalitis due to Naegleria fowleri: The First Imported Case in Korea.

Primary amebic meningoencephalitis (PAM) is a rare, but almost always fatal, central nervous system infection caused by Naegleria fowleri, which are thermophilic free-living amoeba. Here, we report the first case of PAM detected in South Korea, probably imported from Thailand. Despite antimicrobial treatment for N. fowleri infection with a combination of intravenous liposomal amphotericin B, fluconazole, azithromycin, and oral rifampin, the patient died 13 days after the onset of symptoms. Clinicians in South Korea treating severe meningoencephalitis, especially in individuals returning from tropical areas, are encouraged to include PAM in the differential diagnoses, given the accelerated global warming and increased overseas trips.

Risk factors for mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: impact of appropriate antimicrobial therapy.

This study investigated predictors associated with 14-day mortality, and focused especially on the impact of appropriate antimicrobial treatment among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia. This retrospective study was performed at a tertiary care hospital in Korea from June 2007 to June 2010. Antibiotic therapy was considered appropriate if the antibiotics were administered via an appropriate route within 24 hr after the result of blood culture, had in vitro sensitivity to isolated strains, and of an adequate dosage according to the current guidelines. Ninety-five patients with A. baumannii bacteremia were included; of these, 53 (55.8%) were infected with CRAB. The overall infection-related 14-day mortality was higher in patients receiving inappropriate antimicrobial therapy than in patients receiving appropriate therapy (59.5% [22/37] vs 13.8% [8/58], P < 0.05). Multivariate analysis showed that septic shock (OR 10.5, 95% CI, 1.93-57.4; P = 0.006), carbapenem-resistance (OR 7.29, 95% CI 1.57-33.8; P = 0.01), pneumonia as a source of bacteremia (OR 5.29, 95% CI 1.07-26.1; P = 0.04), and inappropriate antimicrobial therapy (OR 8.05, 95% CI 1.65-39.2; P = 0.009) were independent risk factors for 14-day mortality. Early definite antimicrobial therapy had an influence on favorable outcomes in patients with A. baumannii bacteremia.

Analysis of Clinical Characteristics and Laboratory Data Related to the Prognosis of Korean Severe Fever with Thrombocytopenia Syndrome Patients: A Single-Center Study.

Background: Severe fever with thrombocytopenia syndrome (SFTS), an emerging viral infectious disease, is mainly transmitted by ticks in the surrounding environment. Clinical progress and risk factors for prognosis in SFTS patients were not yet fully understood. Thus, the objective of this study was to analyze clinical progression and laboratory data related to the prognosis of South Korean SFTS patients in a single institution from 2014 to 2021. Materials and Methods: Fifty-three confirmed SFTS patients from August 2014 to September 2021 at Gyeongsang National University Hospital (GNUH) in Jinju, South Korea were enrolled. Electronic medical records of SFTS patients' demographic features, clinical data, and laboratory data were retrospectively reviewed. Risk factors for fatality were statistically analyzed by classifying enrolled patients into fatal and non-fatal groups. Results: The mean age of patients in the fatal group was significantly higher than that in the non-fatal group (p = 0.036). Hemorrhagic manifestations (p = 0.001) and multiple organ dysfunction (MOD) (p < 0.001) were significantly common in the fatal group. Age, hemorrhagic manifestations, and MOD were also associated with death (p = 0.001, p = 0.008, and p = 0.041, respectively), with adjusted hazard ratios (aHRs) of 1.14, 18.25, and 2.36, respectively. Onset of illness to admission was also significantly associated with death (p = 0.005), with aHR of 0.48. Age, interval from onset of illness to admission, hemorrhagic manifestations, and MOD were found to be variables related to the fatality of SFTS patients. Conclusion: Laboratory test results showed a significant difference between the fatal group and the non-fatal group, but they did not have a statistically significant effect on the prognosis of SFTS patients.

Real World Experience with Regdanvimab Treatment of Mild-to-Moderate Coronavirus Disease-19 in a COVID-19 Designated Hospital of Korea.

BACKGROUND: Real-world clinical data concerning regdanvimab, a monoclonal antibody treatment for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), are urgently needed. Here, we describe our experience with regdanvimab. MATERIALS AND METHODS: This retrospective cohort study enrolled high-risk adults with mild-to-moderate COVID-19 who were admitted to a dedicated COVID-19 hospital in Korea from March to September 2021. We used multiple logistic regression and propensity score-matching to compare the outcomes of patients who did or did not receive regdanvimab. The primary outcome was in-hospital progression to severe or critical status, or death. RESULTS: Of 586 patients eligible for regdanvimab, 256 patients who received regdanvimab and 251 untreated patients were included. The median age was 66 years and 47.5% were men. The most common underlying illnesses were hypertension (53.8%) and diabetes (36.9%). Patients were admitted to the hospital at a median of 2 days after symptom onset; regdanvimab was administered at a median of 3 days after symptom onset. Multivariate analysis indicated that regdanvimab significantly reduced the risk of disease progression during hospitalization [odds ratio (OR): 0.285; 95% confidence interval (CI): 0.144 - 0.564]. In a 1:1 propensity score-matched cohort (172 patients in either group), regdanvimab also decreased the risk of progression (OR: 0.162; 95% CI: 0.068 - 0.386). CONCLUSION: In high-risk patients with mild-to-moderate COVID-19, regdanvimab decreased the risk of progression to severe COVID-19.

Changes in the characteristics of community-onset fluoroquinolone-resistant Escherichia coli isolates causing community-acquired acute pyelonephritis in South Korea.

PURPOSE: This study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea. METHODS: Blood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of ß-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010-2011. RESULTS: A total of 300 and 346 isolates were identified in 2010-2011 and 2017-2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010-2011 and 2017-2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P < 0.001), were observed among FQ-R isolates in 2017-2018 than among those in 2010-2011. A higher proportion of ST131 isolates (27.6% vs. 66.2%, P < 0.001), as well as isolates that had extended-spectrum ß-lactamase (ESBL)/plasmid-mediated AmpC ß-lactamase (PABL) (23.7% vs. 79.2%, P < 0.001), was observed in 2017-2018 than in 2010-2011. Further, more PMQR determinants (11.8% vs. 40.8%, P < 0.001) were observed in 2017-2018 than in 2010-2011. CONCLUSIONS: Among uropathogenic FQ-R E. coli isolates in South Korea, the prevalence of ST131 and the proportion of isolates containing ESBL and/or PMQR determinants have increased.

Appropriateness of antibiotic prescriptions during hospitalization and ambulatory care: a multicentre prevalence survey in Korea.

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.

Treatment effect of nafamostat mesylate in patients with COVID-19 pneumonia: study protocol for a randomized controlled trial.

BACKGROUND: This study is designed to evaluate the main hypothesis that nafamostat mesilate with standard therapy improves the severity and mortality rate in patients with COVID-19 pneumonia. METHODS: We conduct a randomized, open type, multi-institute/center, 2-group clinical trial with COVID-19 pneumonia patients in Korea. Eighty four patients with COVID-19 pneumonia are randomly assigned to intervention group or control group. Patients in intervention group receive the standard therapy with a dose of 0.1 to 0.2 mg/kg/h (2.4 to 4.8 mg/kg/day) of nafamostat mesilate. Patients in control group receive the standard therapy such as lopinavir/ritonavir, hydroxychloroquine, oxygen therapy, non-invasive and invasive ventilator, antibiotic therapy, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO). The primary outcome is proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status, as well as secondary outcome comprised change in National Early Warning Score, duration of hospitalization, incidence of new-non-invasive ventilation or high flow oxygen use or ventilator, mortality at day 28, viral load change, and adverse events. DISCUSSION: Our study contributes to the establishment of therapeutic strategy in COVID-19 pneumonia by evaluating the therapeutic effect and safety of nafamostat mesilate. TRIAL REGISTRATION: ClinicalTrials.gov NCT04418128. Registered on 5 June 2020.