Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trial.

Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18-64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63-3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68-14.32) also satisfied the non-inferiority criterion (95% CI lower limit > -5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

Clinically differential diagnosis of human granulocytic anaplasmosis and severe fever with thrombocytopenia syndrome.

This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Use of Antibiotics Within the Last 14 Days of Life in Korean Patients: A Nationwide Study.

BACKGROUND: Antimicrobial prescriptions for serious chronic or acute illness nearing its end stages raise concerns about the potential for futile use, adverse events, increased multidrug-resistant organisms, and significant patient and social cost burdens. This study investigated the nationwide situation of how antibiotics are prescribed to patients during the last 14 days of life to guide future actions. METHODS: This nationwide multicenter retrospective cohort study was conducted at 13 hospitals in South Korea from November 1 to December 31, 2018. All decedents were included in the study. Antibiotic use during the last two weeks of their lives was investigated. RESULTS: A total of 1,201 (88.9%) patients received a median of two antimicrobial agents during the last two weeks of their lives. Carbapenems were prescribed to approximately half of the patients (44.4%) in the highest amount (301.2 days of therapy per 1,000 patient-days). Among the patients receiving antimicrobial agents, 63.6% were inappropriate and only 327 patients (27.2%) were referred by infectious disease specialists. The use of carbapenem (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.13-2.03; P = 0.006), underlying cancer (OR, 1.56; 95% CI, 1.20-2.01, P = 0.047), underlying cerebrovascular disease (OR, 1.88; 95% CI, 1.23-2.89, P = 0.004), and no microbiological testing (OR, 1.79; 95% CI, 1.15-2.73; P = 0.010) were independent predictors for inappropriate antibiotic prescribing. CONCLUSION: A considerable number of antimicrobial agents are administered to patients with chronic or acute illnesses nearing their end-of-life, a high proportion of which are prescribed inappropriately. Consultation with an infectious disease specialist, in addition to an antimicrobial stewardship program, may be necessary to induce the optimal use of antibiotics.

Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial.

Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19-85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19-55 years; stage II, 240 healthy adults aged 19-85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Viral Load as a Factor Affecting the Fatality of Patients Suffering from Severe Fever with Thrombocytopenia Syndrome.

The clinical characteristics and the effect of viral RNA loads on fatality in 56 patients with severe fever with thrombocytopenia syndrome (SFTS) were analyzed. The non-survival group (12 patients) demonstrated a significantly higher mean age (77 years) than the survival group (44 patients, 65 years) (p = 0.003). The survival rates were 91.7% and 8.3% in patients with Ct values ≥30 and differed significantly (p = 0.001) in the survival and non-survival groups, respectively. The survival rates were 52.4% and 47.6% in patients with viral copy numbers ≥10,000 and 94.3% and 5.7% in patients with viral copy numbers <10,000 in the survival and non-survival groups, respectively (p = 0.001). In a multivariate analysis, viral copy numbers and initial Acute Psychologic Assessment and Chronic Health Evaluation II (APACHE II) scores were identified as the factors affecting fatality (p = 0.015 and 0.011, respectively). SFTS viral RNA loads can be useful markers for the clinical prediction of mortality and survival.

Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study's scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.'s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. METHODS: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. RESULTS: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03-13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26-14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). CONCLUSION: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Persistent serotype 3 and 19A invasive pneumococcal diseases in adults in vaccine era: Serotype-dependent difference in ceftriaxone susceptibility.

BACKGROUND: Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era. METHODS: Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates. RESULTS: A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180. CONCLUSIONS: PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.

Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity.

A recently developed treatment strategy for lung cancer that combines immune checkpoint inhibitors with chemotherapy has been applied as a standard treatment for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and it has improved the outcomes of chemotherapy. Maintenance treatment with anti-PD-1 antibody (aPD-1) enhances the effect of immunochemical combination therapy and improves therapeutic efficacy, which contributes toward a significant improvement in patient survival rates. The AXL receptor tyrosine kinase (AXL), which is expressed in tumor cells, plays an essential role in the resistance of cancers to chemotherapy and immunotherapy, and stimulates signaling associated with epithelial-mesenchymal transition (EMT) in metastatic cancer. AXL is thus an attractive target for controlling resistance to anti-tumor therapies. In this study, we examined the effect of AXL inhibitors on immune activation and tumor growth in TC1 and C3PQ mouse tumor models, in the context of clinical immunotherapy/chemotherapy and maintenance treatment, using an aPD-1 with/without pemetrexed. To determine the optimal timing for administration of SKI-G-801, an AXL inhibitor, we investigated its anti-tumor effects based on inclusion at the immunochemotherapy and maintenance therapy stages. We also performed flow cytometry-based immune profiling of myeloid cells and lymphoid cells at different points in the treatment schedule, to investigate the immune activation and anti-tumor effects of the AXL inhibitor. The addition of SKI-G-801 to the immune checkpoint inhibitor and chemotherapy stage, as well as the maintenance therapy stage, produced the best anti-tumor results, and significant tumor growth inhibition was observed in both the TC1 and C3PQ models. Both models also exhibited increased proportion of effector memory helper T cells and increased expression of CD86+ macrophages. Especially, regulatory T cells were significantly reduced in the TC1 tumor model and there was an increase in central memory cytotoxic T cell infiltration and an increased proportion of macrophages with high CD80 expression in the C3PQ tumor model. These results suggest increased infiltration of T cells, consistent with previous studies using AXL inhibitors. It is expected that the results from this study will serve as a stepping stone for clinical research to improve the existing standard of care.

Comparison of RT-PCR, RT-nested PCRs, and real-time PCR for diagnosis of severe fever with thrombocytopenia syndrome: a prospective study.

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset.

Effects of education methods on self-efficacy of smoking cessation counseling among medical students.

BACKGROUND: Medical students need to receive training in providing smoking cessation counseling to provide effective smoking cessation interventions to smokers when they become doctors. This study examined the smoking cessation education curricula and factors affecting counseling self-efficacy (CSE) in smoking cessation treatment among medical students. METHODS: In a multicenter cross-sectional study, we obtained demographic information, personal history of tobacco use and intention to quit smoking, exposure to secondhand smoke in the school premises during the past week, the experience of learning about tobacco in each medical school, tobacco-related medical knowledge, and self-efficacy in smoking cessation counseling on medical students of four Korean medical schools. RESULTS: Among 1,416 medical students eligible, 313 (22.1%) students completed a self-administered questionnaire. Only 20.3% of the students reported positive CSE on smoking cessation. The factors affecting positive CSE were scores of ≥ 60 on tobacco-related medical knowledge, smoking experience, and blended learning (p = 0.014, 0.005, and 0.015, respectively). CONCLUSION: This study shows that high scores in tobacco-related medical knowledge and blended learning are correlated with positive CSE for smoking cessation counseling.

Effects of steroid therapy in patients with severe fever with Thrombocytopenia syndrome: A multicenter clinical cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. METHODS: A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. RESULTS: Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70-30.73] vs. 24.9 (95% CI 21.21-28.53], P = .022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005). CONCLUSIONS: After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14).

Psychological distress among infectious disease physicians during the response to the COVID-19 outbreak in the Republic of Korea.

BACKGROUND: This study aimed to investigate psychological distress among infectious disease (ID) physicians during the coronavirus disease 2019 (COVID-19) outbreak in the Republic of Korea. METHODS: Using an online-based survey link sent via text message and email, we conducted a survey from April 21 to 25, 2020, targeting all ID physicians currently working in ID (n = 265). The questionnaire was based on the Maslach Burnout Inventory-Human Services Survey and the Depression, Anxiety, and Stress Scales, and information was collected on factors protecting against psychological distress and difficulties in relation to COVID-19. RESULTS: Of 265 ID physicians, 115 (43.3%) responded, showing burnout (97, 90.4%), depression (20, 17.4%), anxiety (23, 20.0%), and stress (5, 4.3%). There were no differences in terms of distress between ID physicians who were directly involved in the care of patients with COVID-19 or not. Greater than 50% of physicians valued their work and felt recognized by others, whereas < 10% indicated that sufficient human and financial support and private time had been provided during the outbreak. The most challenging issues concerned a lack of attending physicians caring for COVID-19 patients or infection control practitioners, a shortage of personal protective equipment or airborne infection isolation rooms, pressure for research, and lack of guidelines for COVID-19 management. CONCLUSIONS: During the COVID-19 outbreak in the Republic of Korea, most respondents reported psychological distress. Preparing strategies to secure human resources are crucial to prepare effectively for future epidemics and pandemics.

First identification of Anaplasma phagocytophilum in both a biting tick Ixodes nipponensis and a patient in Korea: a case report.

BACKGROUND: Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum. To date, there have been no reported cases of A. phagocytophilum infection found in both the biting tick and the patient following a tick bite. CASE PRESENTATION: An 81-year-old woman presented with fever following a tick bite, with the tick still intact on her body. The patient was diagnosed with HGA. The tick was identified as Ixodes nipponensis by morphological and molecular biological detection methods targeting the 16S rRNA gene. The patient's blood was cultured after inoculation into the human promyelocytic leukemia cell line HL-60. A. phagocytophilum growth was confirmed via culture and isolation. A. phagocytophilum was identified in both the tick and the patient's blood by Anaplasma-specific groEL- and ankA-based nested polymerase chain reaction followed by sequencing. Moreover, a four-fold elevation in antibodies was observed in the patient's blood. CONCLUSION: We report a case of a patient diagnosed with HGA following admission for fever due to a tick bite. A. phagocytophilum was identified in both the tick and the patient, and A. phagocytophilum was successfully cultured. The present study suggests the need to investigate the possible incrimination of I. nipponensis as a vector for HGA in Korea.

Human resources required for antimicrobial stewardship activities for hospitalized patients in Korea.

OBJECTIVES: We calculated the human resources required for an antimicrobial stewardship program (ASP) in Korean hospitals. DESIGN: Multicenter retrospective study. SETTING: Eight Korean hospitals ranging in size from 295 to 1,337 beds. METHODS: The time required for performing ASP activities for all hospitalized patients under antibiotic therapy was estimated and converted into hours per week. The actual time spent on patient reviews of each ASP activity was measured with a small number of cases, then the total time was estimated by applying the determined times to a larger number of cases. Full-time equivalents (FTEs) were measured according to labor laws in Korea (52 hours per week). RESULTS: In total, 225 cases were reviewed to measure time spent on patient reviews. The median time spent per patient review for ASP activities ranged from 10 to 16 minutes. The total time spent on the review for all hospitalized patients was estimated using the observed number of ASP activities for 1,534 patients who underwent antibiotic therapy on surveillance days. The most commonly observed ASP activity was 'review of surgical prophylactic antibiotics' (32.7%), followed by 'appropriate antibiotics recommendations for patients with suspected infection without a proven site of infection but without causative pathogens' (28.6%). The personnel requirement was calculated as 1.20 FTEs (interquartile range [IQR], 1.02-1.38) per 100 beds and 2.28 FTEs (IQR, 1.93-2.62) per 100 patients who underwent antibiotic therapy, respectively. CONCLUSION: The estimated time required for human resources performing extensive ASP activities on all hospitalized patients undergoing antibiotic therapy in Korean hospitals was ~1.20 FTEs (IQR, 1.02-1.38) per 100 beds.

What should we prepare for the next coronavirus disease 2019 outbreak? A survey on the opinions of infectious diseases specialists in South Korea.

BACKGROUND/AIMS: This study aimed to collect information on the opinions of Korean infectious disease (ID) experts on coronavirus disease 2019 (COVID-19) and related issues in preparation for a future outbreak. METHODS: A survey was conducted over the course of 5 days (from April 21 to 25, 2020), targeting all adult ID specialists currently in the medical field in South Korea (n = 265). An online-based survey was forwarded via text message and e-mail. Only one response was accepted from each participant. RESULTS: Of these 265 ID specialists gotten to, 132 (49.8%) responded. The highest proportion of the respondents envisaged the current COVID-19 outbreak to end after December 2020 (47.7% for the domestic Korean outbreak and 70.5% for the global pandemic); moreover, 60.7% of them stated that a second nationwide wave is likely to occur between September and December 2020 in South Korea. N95 respirators were considered to be the most important item in hospitals in preparation for a second wave. The most important policy to be implemented at the national level was securing national hospitals designated for the treatment of ID (67.4%). CONCLUSION: ID experts in South Korea believe that the COVID-19 pandemic may not be easily controlled and that a second nationwide wave is likely to occur in South Korea. Our results indicate that Korean ID specialists believe that a high level of preparation is needed in various aspects, including the procurement of personal protective equipment, to respond efficiently to a second outbreak.

Effect of colistin-based antibiotic combinations on the eradication of persister cells in Pseudomonas aeruginosa.

OBJECTIVES: Persister cells are responsible for antibiotic treatment failure and the emergence of antibiotic resistance. The synergistic lethal effects of antibiotic combinations on persister cells were investigated using Pseudomonas aeruginosa isolates. METHODS: Persister assays were performed on P. aeruginosa clinical isolates using colistin, amikacin, ciprofloxacin and cefepime, individually and in combination. ATP concentrations were measured and morphological changes in persister cells were observed using transmission electron microscopy (TEM). The expression of relA, spoT and obg genes was evaluated and persister-cell formation was investigated in a relA and spoT double mutant (ΔrelAΔspoT). RESULTS: The P. aeruginosa persister cells were eradicated upon exposure to the colistin-based antibiotic combination colistin + ciprofloxacin. Simultaneous treatment with both antibiotics, rather than sequential treatment, caused more effective eradication. The intracellular ATP concentration was most reduced in colistin persisters. While the spoT gene was only overexpressed in colistin-persister cells, the relA gene was overexpressed in all persister cells compared with untreated parent cells. TEM analysis suggested the possibility that persister cells might be formed by different mechanisms depending on the antibiotic. Cell elongation and cell wall or membrane damage in colistin persisters, DNA condensation in amikacin persisters and outer membrane vesicles in ciprofloxacin persisters were identified. CONCLUSIONS: In P. aeruginosa, the colistin-based antibiotic combination (colistin + ciprofloxacin) was effective for the eradication of persister cells, probably due to the different persister cell-formation mechanisms between the two antibiotics. Simultaneous, rather than sequential, treatment with two antibiotics could be more effective for eradicating persister P. aeruginosa cells.