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Although CD4+CD25+FOXP3+ regulatory T (TREG) cells have been studied in patients with COVID-19, changes in the TREG cell population have not been longitudinally examined during the course of COVID-19. In this study, we longitudinally investigated the quantitative and qualitative changes in the TREG cell population in patients with COVID-19. We found that the frequencies of total TREG cells and CD45RA−FOXP3hi activated TREG cells were significantly increased 15–28 d postsymptom onset in severe patients, but not in mild patients. TREG cells from severe patients exhibited not only increased proliferation but also enhanced apoptosis, suggesting functional derangement of the TREG cell population during severe COVID-19. The suppressive functions of the TREG cell population did not differ between patients with severe versus mild COVID-19. The frequency of TREG cells inversely correlated with SARS-CoV-2–specific cytokine production by CD4+ T cells and their polyfunctionality in patients with mild disease, suggesting that TREG cells are major regulators of virus-specific CD4+ T cell responses during mild COVID-19. However, such correlations were not observed in patients with severe disease. Thus, in this study, we describe distinctive changes in the TREG cell population in patients with severe and mild COVID-19. Our study provides a deep understanding of host immune responses upon SARS-CoV-2 infection in regard to TREG cells.

Objectives We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients. Methods We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens. Results The seropositivity rate persisted for up to 4 years (50.7–56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT50, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection. Discussion The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.

Background Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia occur within a few days after the onset of bacteremia, 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 bacteremia. Methods All patients with CRAB bacteremia in 10 hospitals during a 1-year study period were identified. We prospectively collected patients’ clinical data, including microbiological and demographic data, underlying comorbidities, origin of bacteremia, severity of illness, antibiotic therapy, and mortality. 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 A total of 212 CRAB bacteremia 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 were significantly higher in 30-day deaths than 30-day survivors. These factors of clinical severity were also significantly higher in patients with EM than those with LM. While urinary tract infection as the factor of 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. Appropriate empirical antibiotic therapy was associated with reduced risk of EM. Conclusion The difference between risk factors for EM and LM was identified in this study. Our data suggest that a large proportion of CRAB bacteremia with high severity progress 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. Disclosures All Authors: No reported disclosures.

Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (50 years) in Korea.We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients' electronic medical records were reviewed to identify clinical characteristics.During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI)25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754-18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439-35.192), highest creatinine1.5 mg/dL (OR, 17.631; 95% CI, 8.321-37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061-18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI25 kg/m²), and the one remaining patient died from a secondary infection.About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

BACKGROUND Staphylococcus aureus bacteremia (SAB) is a common and serious infection with a high mortality. Patients with chronic kidney disease (CKD) are vulnerable to SAB, but there have been few studies performed on the clinical characteristics and outcomes of SAB in CKD patients stratified by dialysis. We aimed to estimate the all-cause mortality and identify its predictors in patients with CKD. MATERIALS AND METHODS We conducted a retrospective study on the patients with SAB hospitalized in a tertiary care center in Korea between March 2014 and December 2018. Kaplan-Meier analysis was performed to compare all-cause mortality following SAB among patients with non-dialysis dependent CKD (ND-CKD), those receiving dialysis, and those without CKD (non-CKD). The predictors of mortality among CKD patients were analyzed by Cox proportional hazards regression. RESULTS As a total, 278 SAB of 43 ND-CKD (31 males), 58 dialysis (39 males), and 177 non-CKD (112 males) patients were included. The 30-day mortality was 39.5% in ND-CKD, 27.6% in dialysis, and 7.9% in non-CKD patients. The hazard ratio of all-cause mortality following SAB in ND-CKD was 2.335 (95% confidence interval, 1.203 - 4.531; P = 0.003), compared to non-CKD patients. For methicillin-resistant S. aureus bacteremia (MRSAB), the hazard ratio of all-cause mortality in ND-CKD was 2.628 (95% CI, 1.074 - 6.435; P = 0.011), compared to dialysis patients. Appropriate antibiotics

Background Regdanvimab (CT-P59) is a monoclonal antibody with neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on part 1 of a 2-part randomized, placebo-controlled, double-blind study for patients with mild-to-moderate coronavirus disease 2019 (COVID-19). Methods Outpatients with mild-to-moderate COVID-19 received a single dose of regdanvimab 40 mg/kg (n = 100), regdanvimab 80 mg/kg (n = 103), or placebo (n = 104). The primary end points were time to negative conversion of SARS-CoV-2 from nasopharyngeal swab based on quantitative reverse transcription polymerase chain reaction (RT-qPCR) up to day 28 and time to clinical recovery up to day 14. Secondary end points included the proportion of patients requiring hospitalization, oxygen therapy, or mortality due to COVID-19. Results Median (95% CI) time to negative conversion of RT-qPCR was 12.8 (9.0–12.9) days with regdanvimab 40 mg/kg, 11.9 (8.9–12.9) days with regdanvimab 80 mg/kg, and 12.9 (12.7–13.9) days with placebo. Median (95% CI) time to clinical recovery was 5.3 (4.0–6.8) days with regdanvimab 40 mg/kg, 6.2 (5.5–7.9) days with regdanvimab 80 mg/kg, and 8.8 (6.8–11.6) days with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with regdanvimab 40 mg/kg (4.0% [1.6%–9.8%]) and regdanvimab 80 mg/kg (4.9% [2.1%–10.9%]) vs placebo (8.7% [4.6%–15.6%]). No serious treatment-emergent adverse events or deaths occurred. Conclusions Regdanvimab showed a trend toward a minor decrease in time to negative conversion of RT-qPCR results compared with placebo and reduced the need for hospitalization and oxygen therapy in patients with mild-to-moderate COVID-19. Clinical trial registration. NCT04602000 and EudraCT 2020-003369-20.

Background: Carbapenem-resistance (CR) causes poor clinical outcomes and has limited treatment options. We aim to evaluate the differences in clinical characteristics and impact of carbapenem-resistance on outcomes between Acinetobacter baumannii (ABA) and Pseudomonas aeruginosa (PAE) bacteraemia. Methods: We prospectively identified all patients with ABA and PAE bacteraemia in 10 hospitals over a 1-year period and collected their detailed clinical information. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrence within 30 days.Results: We included 304 ABA and 241 PAE bacteraemia cases. CR was detected in 216 ABA (71%) and 55 PAE (23%). Treatment failure was significantly higher in CR-ABA than in CR-PAE (60.6% vs. 34.5%, P = 0.001). Multivariate analyses were stratified by patient data according to CR and the appropriateness of empirical therapy. For ABA patients, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. Pneumonia was a significant risk factor in the appropriate group. For PAE patients, 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 ABA for treatment failure in both the inappropriate (adjusted odds ratio [aOR]: 6.17, 95% confidence interval [CI]: 1.13-33.75, P = 0.036) and appropriate empirical treatment groups (aOR: 4.15, 95% CI: 1.16-14.84, P = 0.029), but not for patients with PAE bacteraemia. Conclusions: We demonstrated significant differences in the clinical characteristics and impact of CR on the clinical outcomes between ABA and PAE bacteraemia. Our findings suggest that different approaches may be needed to treat ABA and PAE bacteraemia.

Background Our understanding of adaptive immune responses in COVID-19 patients is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient. Objective We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19. Methods We performed RNA sequencing (RNA-seq) and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved peripheral blood mononuclear cells (PBMCs). Results In RNA-seq analysis, the NK cells exhibited distinctive features compared to healthy donors, with significant enrichment of pro-inflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56dimCD16neg (uCD56dim) NK cell population expanded in cryopreserved PBMCs from COVID-19 patients regardless of disease severity, accompanied by decreased NK cell cytotoxicity. The NK cell population was rapidly normalized alongside the disappearance of uCD56dim NK cells and the recovery of NK cell cytotoxicity in mild COVID-19 patients, but this occurred slowly in severe COVID-19 patients. Conclusion The current longitudinal study provides a deep understanding of the NK cell biology in COVID-19., Graphical abstract

To evaluate the impacts of fluconazole minimum inhibitory concentration (MIC) according to primary antifungal agents on Candida glabrata bloodstream infection (BSI), a multicenter retrospective cohort study was conducted in Korea, concerning the time period from January 2010 to February 2016. A total of 197 adult patients with C. glabrata BSI were included in the study, and neutropenia (P = 0.026), APACHE II score (P = 0.004), and fluconazole resistance (HR 3.960, 95% CI 1.395-11.246, P = 0.010) were associated with 30-day mortality in multivariate analysis. In subgroup analysis, fluconazole MIC = 32 μg/mL in the azole-treated group (HR 6.691, 95% CI 1.569-28.542, P = 0.010) and fluconazole MIC ≥ 64 μg/mL in the non-azole-treated group (HR 3.337, 95% CI 1.183-9.411, P = 0.023) showed the highest hazard ratio (HR) for 30-day mortality. Increased fluconazole MIC was associated with poor outcome both in azole- and non-azole-treated patients with C. glabrata BSI.

Background Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This disease, which is quickly spreading worldwide, has high potential for infection and causes rapid progression of lung lesions, resulting in a high mortality rate. This study aimed to investigate the effects of SARS-CoV-2 infection on renal function in patients with COVID-19. Methods From February 21 to April 24, 2020, 66 patients diagnosed with COVID-19 at Chungnam National University Hospital were analyzed; all patients underwent routine urinalysis and were tested for serum creatinine, urine protein to creatinine ratio (PCR), and urine albumin to creatinine ratio (ACR). Results Acute kidney injury (AKI) occurred in 3 (4.5%) of the 66 patients, and 1 patient with AKI stage 3 underwent hemodialysis. Upon follow-up, all 3 patients recovered normal renal function. Compared with patients with mild COVID-19, AKI (n = 3) occurred in patients with severe COVID-19, of whom both urine PCR and ACR were markedly increased. Conclusion The incidence of AKI was not high in COVID-19 patients. The lower mortality rate in SARS-CoV-2 infection compared with previous Middle East respiratory syndrome and SARS-CoV infections is thought to be associated with a low incidence of dysfunction in organs other than the lungs., Graphical Abstract

To evaluate clinical features and prognostic factors of non-albicans candidemia, we conducted a retrospective multicenter cohort study at 7 university hospitals in Korea from January 2010 to February 2016. A total of 721 patients with non-albicans candidemia were included in the analysis. C. tropicalis was most commonly identified (36.5%), followed by C. glabrata (27.2%), C. parapsilosis (25.7%), and C. krusei (2.4%). Clinical presentation of C. tropicalis candidemia was most severe with highest median C-reactive protein level (10.1 mg/dL) and Acute Physiology and Chronic Health Evaluation II score (14, both P ≪ 0.05). C. tropicalis showed the highest 14- and 30-day mortality (28.9% and 44.1%). In multivariate analysis, C. tropicalis infection was significantly related with 14- (P = 0.005) and 30-day mortality (P = 0.033). In conclusion, C. tropicalis infection presented most severely and showed worst clinical outcome among non-albicans candidemia.

The microbiological characteristics of Staphylococcus aureus causing infective endocarditis (IE) have not been investigated thoroughly. We compared the characteristics of S. aureus isolates from patients with and without IE. Cases of S. aureus bacteremia (SAB) were collected from 10 hospitals over 7 years. Cases of native valve IE were matched with non-IE controls according to the following criteria: central-line-associated infection, community-acquired infection, methicillin susceptibility, and if possible, the primary site of infection. Genes coding virulence factors were analyzed using multiplex polymerase chain reactions. Fibrinogen and fibronectin-binding properties were assessed using in vitro binding assays. The fibronectin-binding protein A gene (fnbpA) was sequenced. Of 2,365 cases of SAB, 92 had IE. After matching, 37 pairs of S. aureus isolates from the IE cases and non-IE controls were compared; fnbpA was detected in 91.9% of the IE isolates and 100% of the non-IE isolates (p = 0.24). While the fibrinogen binding ratio was similar (1.07 ± 0.33 vs. 1.08 ± 0.26, p = 0.89), the fibronectin-binding ratio was significantly higher in the IE-group (1.31 ± 0.42 vs. 1.06 ± 0.31, p = 0.01). The proportions of major single-nucleotide polymorphisms in fnbpA were as follows: E652D (2.9% vs. 2.7%), H782Q (65.6% vs. 60.6%), and K786N (65.6% vs. 72.7%). The fibronectin-binding ratio was positively correlated with the number of SNPs present in IE cases (p < 0.001) but not in the non-IE controls (p = 0.124). Fibronectin-binding might play a key role in SAB IE. However, the degree of binding may be mediated by genetic variability between isolates.

Background: A pooling test is a useful tool for mass screening of coronavirus disease 2019 (COVID-19) in the pandemic era We aimed to optimize a simple two-step pooling test by estimating the optimal pool size using experimental and mathematical validation Materials and Methods: Experimental pools were created by mixing one positive respiratory sample with various numbers of negative samples We selected positive samples with cycle threshold (Ct) values greater than 32 to validate the efficiency of the pooling test assuming a high likelihood of false-negative results due to low viral loads The positivities of the experimental pools were investigated with a single reverse-transcription polymerase chain reaction (RT-PCR) using the U-TOP™ COVID-19 Detection Kit Plus (Seasun Biomaterials, Daejeon, Korea) We used the Dorfman equation to calculate the optimal size of a pooling test mathematically Results: Viral RNA could be detected in a pool with a size up to 11, even if the Ct value of a positive sample was about 35 The Dorfman equation showed that the optimal number of samples in a pool was 11 when the prevalence was assumed to be 0 66% based on the test positivity in Daejeon, Korea from April 1, 2020 to November 10, 2020 The efficiency of the pooling test was 6 2, which can save 83 9 of 100 individual tests Conclusion: Eleven samples in a pool were validated optimal experimentally assuming a prevalence of 0 66% The pool size needs modification as the pandemic progresses;thus, the prevalence should be carefully estimated before pooling tests are conducted Copyright © 2021 by The Korean Society of Infectious Diseases

Background A Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 started by a single imported case and was amplified by intra- and inter-hospital transmission. We describe two hospital outbreaks of MERS-CoV infection in Daejeon caused by a single patient who was infected by the first Korean case of MERS. Materials and Methods Demographic and clinical information involving MERS cases in the Daejeon cluster were retrospectively collected and potential contacts and exposures were assessed. The incubation periods and serial intervals were estimated. Viral RNAs were extracted from respiratory tract samples obtained from the index case, four secondary cases and one tertiary case from each hospital. The partial S2 domain of the MERS-CoV spike was sequenced. Results In Daejeon, a MERS patient (the index case) was hospitalized at Hospital A in the first week of illness and was transferred to Hospital B because of pneumonia progression in the second week of illness, where he received a bronchoscopic examination and nebulizer therapy. A total of 23 secondary cases (10 in Hospital A and 13 in Hospital B) were detected among patients and caregivers who stayed on the same ward with the index case. There were no secondary cases among healthcare workers. Among close hospital contacts, the secondary attack rate was 15.8% (12/76) in Hospital A and 14.3% (10/70) in Hospital B. However, considering the exposure duration, the incidence rate was higher in Hospital B (7.7/100 exposure-days) than Hospital A (3.4/100 exposure-days). In Hospital B, the median incubation period was shorter (4.6 days vs. 10.8 days), the median time to pneumonia development was faster (3 days vs. 6 days) and mortality was higher (70% vs. 30.8%) than in Hospital A. MERS-CoV isolates from 11 cases formed a single monophyletic clade, with the closest similarity to strains from Riyadh. Conclusion Exposure to the MERS case in the late stage (2nd week) of diseases appeared to increase the risk of transmission and was associated with shorter incubation periods and rapid disease progression among those infected. Early detection and isolation of cases is critical in preventing the spread of MERS in the hospital and decreasing the disease severity among those infected.

Mycobacterium avium complex (MAC) comprises M. intracellulare and M. avium. MAC usually causes pulmonary diseases in individuals with intact immunity, disseminated disease in patients with acquired immunodeficiency syndrome, and cer- vical lymphadenitis. It can also cause cutaneous disease, but musculoskeletal infection is rare. Herein, we present a case of vertebral osteomyelitis due to M. intracellulare in an elderly immunocompetent patient who underwent vertebroplasty. The patient was successfully treated with antimycobacterial drugs without surgical intervention. MAC should be considered as a causative pathogen of vertebral osteomyelitis when the patient has a history of vertebroplasty.

BACKGROUND/AIMS Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. METHODS Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital-onset MDR A. baumannii among patients in the ICUs. RESULTS The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 ± 82.26 defined daily doses per 1,000 patient-days to 94.85 ± 50.98 defined daily doses per 1,000 patient-days (p = 0.016). CONCLUSIONS Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year.

To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as14 or ≥14 days in the SS group and28 or ≥28 days in the LW group.Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05).Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.

Copyright©2015 Korean Geriatric Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/). ▸Received: April 6, 2015 ▸Revised: April 27, 2015 ▸Accepted: May 8, 2015 Address for correspondence: Kyung Mok Sohn, MD Division of Infectious Diseases, Department of Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon 301-721, Korea Tel: +82-42-280-7126, Fax: +82-42-280-8125 E-mail: medone@cnuh.co.kr 관절 내 주사 치료 후 발생한 Staphylococcus lugdunensis에 의한 화농성 슬관절염

Middle East respiratory syndrome (MERS) is an emerging zoonotic viral respiratory disease that was first identified in Saudi Arabia in 2012. In 2015, the largest MERS outbreak outside of the Middle East region occurred in the Republic of Korea. The rapid nosocomial transmission of MERS-coronavirus (MERS-CoV) in Korean health care settings highlighted the importance and urgent need for a rapid and reliable on-site diagnostic assay to implement effective control and preventive measures. Here, the evaluation and validation of two newly developed reverse transcription–insulated isothermal PCR (RT-iiPCR) methods targeting the ORF1a and upE genes of MERS-CoV are described. Compared with World Health Organization-recommended singleplex real-time quantitative RT-PCR (RT-qPCR) assays, both RT-iiPCR assays had comparable analytical sensitivity for the detection of MERS-CoV RNA in tissue culture fluid and in sputum samples spiked with infectious virus. Furthermore, clinical evaluation was performed with sputum samples collected from subjects with acute and chronic respiratory illnesses, including patients infected with MERS-CoV. The overall agreement values between the two RT-iiPCR assays and the reference RT-qPCR assays were 98.06% (95% CI, 94.43%–100%; κ = 0.96) and 99.03% (95% CI, 95.88%–100%; κ = 0.99) for ORF1a and upE assays, respectively. The ORF1a and upE MERS-CoV RT-iiPCR assays coupled with a field-deployable system provide a platform for a highly sensitive and specific on-site tool for diagnosis of MERS-CoV infections.

Vertebral Osteomyelitis caused by Burkholderia cepacia in an Immunocompetent Elderly Patient After Acupuncture Ki Dae Kim, MD, Kyung Mok Sohn, MD, Yeon-Sook Kim, MD, Shinhye Cheon, MD, Chang Hun Song, MD, Jin-Young Youm, MD, Sun Hoe Koo, MD Division of Infectious Diseases, Departments of Neurosurgery, and Laboratory Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea

We report the first case of catheter-related bacteremia caused by Kocuria salsicia in a patient with short bowel syndrome. The pathogen was initially identified as Kocuria varians by a Vitek 2-based assessment, but its 16S rRNA gene sequence showed 100% similarity to K. salsicia. The patient was successfully treated with vancomycin and removal of the catheter.

Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.

The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26., IMPORTANCE Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.

Background/Aims: Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. Methods: Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital-onset MDR A. baumannii among patients in the ICUs. Results: The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 ± 82.26 defined daily doses per 1,000 patient-days to 94.85 ± 50.98 defined daily doses per 1,000 patient-days (p = 0.016). Conclusions: Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year.

Disseminated aspergillosis is very rare in immunocompetent hosts and is typically associated with a poor prognosis. We describe the case of a 66-year-old, immunocompetent man who developed pneumonia, endophthalmitis and probable spondylitis caused by Aspergillus species. The patient was successfully treated with antifungal drugs. We reviewed the English-language literature between 1980 and 2012 for disseminated aspergillosis cases in immunocompetent hosts, using the keywords “dissemin*” and “aspergillo*.” Disseminated aspergillosis in immunocompetent hosts is very rare in the literature. However, awareness of possible dissemination of Aspergillus spp. is necessary in patients who have a probable lung lesion and in cases with unusual presentation of a disseminated infection, even if the patient has no risk factors.

Vancomycin is frequently inappropriately prescribed, especially as empirical treatment. The aim of this study was to evaluate (i) the amount of inappropriate continued empirical vancomycin use as a proportion of total vancomycin use and (ii) the risk factors associated with inappropriate continued empirical vancomycin use. We reviewed the medical records of adult patients who had been prescribed at least one dose of parenterally administered vancomycin between January and June 2012, in a single tertiary care hospital. When empirically prescribed vancomycin treatment was continued after 96 h without documentation of beta-lactam-resistant Gram-positive microorganisms in clinical specimens with significance, the continuation was considered inappropriate, and the amount used thereafter was considered inappropriately used. We identified risk factors associated with inappropriate continued empirical vancomycin use by multiple logistic regression. During the study period, the amount of parenterally administered vancomycin prescribed was 34.2 defined daily doses (DDDs)/1,000 patient-days (1,084 prescriptions for 971 patients). The amount of inappropriate continued empirical vancomycin use was 8.5 DDDs/1,000 patient-days, which represented 24.9% of the total parenterally administered vancomycin used (8.5/34.2 DDDs/1,000 patient-days). By multivariate analyses, inappropriate continued empirical vancomycin use was independently associated with the absence of any documented etiological organism (adjusted odds ratio [aOR], 1.60 [95% confidence interval {CI}, 1.06 to 2.41]) and suspected central nervous system (CNS) infections (aHR, 2.33 [95% CI, 1.20 to 4.50]). Higher Charlson's comorbidity index scores were inversely associated with inappropriate continued empirical vancomycin use (aHR, 0.90 [95% CI, 0.85 to 0.97]). Inappropriate continued empirical vancomycin use represented 24.9% of the total amount of vancomycin prescribed, which indicates room for improvement.

Background: There are few data about long-term respiratory complications following Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection This study aimed to evaluate respiratory functions and radiologic sequelae according to the severity of infection one year after the patients experienced MERS-CoV infection Methods: A total of 73 patients undergoing MERS-CoV infection during the 2015 MERS outbreak in South Korea were enrolled in this prospective multicenter study Pulmonary function tests and 6-minute walking tests were performed 1 year after infection Radiologic sequelae was defined as fibrosis or atelectasis on chest computer tomography and severe pneumonia was defined as that requiring oxygen therapy Multivariate linear regression tests were used to evaluate the effect of infection severity on respiratory function Results: At the time of MERS-CoV infection, 18 patients had no pneumonia, 35 experienced mild pneumonia, and 20 did severe pneumonia The median age was not different between groups (P = 0 942) Forced vital capacity (FVC) was 102 6%, 94 9%, and 88 7% in the no, mild, and severe pneumonia group, respectively (P = 0 010) and forced expiratory volume in 1 second was 105 3%, 95 7%, and 91 7% (P = 0 057) Diffusing capacity (DLCO) was significantly lower in the severe pneumonia group than in the no or mild pneumonia group (78 3% vs 89 4% or 88 6%, P = 0 035) In multivariate analyses, FVC and DLCO were significantly correlated with infection severity after adjustment with age, sex, underlying lung disease, and smoking There was no difference in the walking distance of 6 minute tests between groups Radiologic sequelae were shown in 18 8%, 65 6%, and 100% in the no, mild, and severe pneumonia group, respectively (P < 0 001) Conclusion: The patients with more severe pneumonia by MERS-CoV had more impaired respiratory function in one year follow-up, which was compatible with radiologic sequelae Disclosures: All authors: No reported disclosures FAU - Il Jun, Kang

Nak-Hyun Kim, Hei Lim Koo, Pyoeng Gyun Choe, Shinhye Cheon, Moonsuk Kim, Myung Jin Lee, Younghee Jung, Wan Beom Park, Kyoung-Ho Song, Eu Suk Kim, Ji Hwan Bang, Hong Bin Kim, Sang Won Park, Nam Joong Kim, Myoung-don Oh, Eui Chong Kim Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Infection Control Service, Seoul National University Hospital, Seoul, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

Background This study was performed to detect risk factors for Pseudomonas aeruginosa bacteremia in patients with liver cirrhosis. Methods A retrospective case–control study was designed to identify risk factors for P. aeruginosa bacteremia in cirrhotic patients. The cases were cirrhotic patients with P. aeruginosa bacteremia and the controls were cirrhotic patients with Enterobacteriaceae bacteremia. Results Sixty-one cases and the same number of controls were enrolled. In a multivariate analysis, younger age {adjusted odds ratio (aOR) per one year: 0.96, 95% confidence interval: 0.93 - 0.99}, nosocomial acquisition (aOR 3.87, 95% confidence interval: 1.50 - 9.94), preexisting biliary disease (aOR 4.79, 95% confidence interval: 1.92 - 10.47), and recent exposure to immunosuppressive agent (aOR 3.10, 95% confidence interval: 1.23 - 7.82) were associated with P. aeruginosa bacteremia. In the case group the frequency of appropriate initial antibiotic regimens was considerably lower than in the control group: 29.5% vs. 65.6% (P Conclusions Nosocomial acquisition, preexisting biliary disease, and recent use of immunosuppressive agents are strong predictive factors for P. aeruginosa bacteremia in cirrhotic patients.

Serratia에 의한 감염은 대부분 병원 시술이나 수술 혹은 면역 저하와 관련되어 있다. 인간 감염을 일으키는 것으로 S. marcescens가 가장 흔하고 S. liquefaciens도 종종 문제가 된다. 그러나 S. gimesii에 의한 감염 혹은 지역사회 획득 Serratia 척추염은 보고된 적이 없다. 저자들은 고혈압 외에는 건강하게 지내던 환자에서 발생한 경막외 고름을 동반한 S. grimesii에 의한 척추 골수염을 경험하였다. 고름 제거 후 항생제 치료로 호전되어 문헌고찰과 함께 보고하는 바이다.