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The appropriate carbapenem use is a critical concern for patient safety, public health, and 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 comprising of 1,350 decedents. Carbapenem use was universally restricted by computerised authorisation 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 2 weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was 7 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%) were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) without ID consults, 194 (58.2%) were assessed as “not optimal”: 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients within their last days of life, a majority of whom do not require it.

Although body fluid adenosine deaminase (ADA) level is useful for diagnosing tuberculosis but little is known about joint fluid ADA level in tuberculous (TB) arthritis. This study aimed to evaluate the diagnostic value of synovial fluid ADA (SF-ADA) in TB arthritis. Of 43 patients enrolled, nine had confirmed TB arthritis. Fourteen had non-TB septic arthritis, and 20 patients had non-infectious etiologies. The SF-ADA levels were significantly elevated in patients with TB arthritis compared to those with non-infectious origin (P

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

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we show that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. In addition, we confirm increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the critical group. Moreover, enhanced antibody responses and complement activation is associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from six fatal cases, as well as by enhanced hallmark gene set signatures of FcγR signaling and complement activation in myeloid cells of respiratory specimens from critical COVID-19 patients. These results suggest that SARS-CoV-2 infection may drive specific innate immune responses, including eosinophil-mediated inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of critical disease in COVID-19 patients., Graphical Abstract, Kim et al. find that critical COVID-19 is associated with enhanced eosinophil-mediated inflammation when compared to non-critical cases. Increased Th2-biased immune responses, accompanying overt complement activation, are seen in the critical group. These findings suggest that enhanced eosinophil-mediated inflammation and dysregulated humoral responses might be drivers of severe COVID-19.

Despite the worldwide effect of the Coronavirus disease 2019 (COVID-19) pandemic, the underlying mechanisms of fatal viral pneumonia remain elusive. Here, we conducted kinetic profiling of respiratory leukocytes and associated inflammatory mediators to show that severe COVID-19 is associated with delayed but enhanced eosinophilic inflammation when compared to mild cases. In addition, we confirmed increased Th2-biased adaptive immune responses, accompanying overt complement activation, in the severe group. Moreover, enhanced antibody responses and complement activation was associated with disease pathogenesis as evidenced by formation of immune complexes and membrane attack complexes in airways and vasculature of lung biopsies from a fatal case, as well as by enhanced hallmark gene set signatures of FcgR signaling and complement activation in myeloid cells of respiratory specimens from severe COVID-19 patients. We also observed expression of viral antigen in lung epithelial and endothelial cells without producing viruses during late stage of COVID-19, indicating abortive viral infection which may further fuel antibody responses and aggravate immune-complex-mediated inflammation. These results suggest that SARS-CoV-2 infection may drive scripted specific innate immune responses, including eosinophilic inflammation, and subsequent pulmonary pathogenesis via enhanced Th2-biased immune responses, which might be crucial drivers of severe pneumonia in COVID-19 patients.

Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a cytokine storm is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls. Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.

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

Clostridium (Clostridioides) difficile causes toxin-mediated diarrhea and pseudomembranous colitis, primarily among hospital inpatients. Outbreaks of C. difficile infection (CDI) have been caused by strains with acquired antimicrobial resistance, particularly fluoroquinolone resistance, including C. difficile ribotype (RT) 027 in North America and Europe and RT 017, the most common strain in Asia. Despite being the most common cause of hospital-acquired infection in high-income countries, and frequent misuse of antimicrobials in Asia, little is known about CDI in the Asia-Pacific region. We aimed to determine the antimicrobial susceptibility profiles of a collection of C. difficile isolates from the region. C. difficile isolates (n = 414) from a 2014 study of 13 Asia-Pacific countries were tested for susceptibility to moxifloxacin, amoxicillin-clavulanate, erythromycin, clindamycin, rifaximin, metronidazole, vancomycin, and fidaxomicin according to the Clinical and Laboratory Standards Institute's agar dilution method. All isolates were susceptible to metronidazole, vancomycin, amoxicillin-clavulanate, and fidaxomicin. Moxifloxacin resistance was detected in all countries except Australia, all RT 369 and QX 239 strains, and 92.7% of RT 018 and 70.6% of RT 017 strains. All C. difficile RT 012, 369, and QX 239 strains were also resistant to erythromycin and clindamycin. Rifaximin resistance was common in RT 017 strains only (63.2%) and was not detected in Australian, Japanese, or Singaporean isolates. In conclusion, antimicrobial susceptibility of C. difficile varied by strain type and by country. Multiresistance was common in emerging RTs 369 and QX 239 and the most common strain in Asia, RT 017. Ongoing surveillance is clearly warranted.

Background Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a ‘cytokine storm’ is involved in the pathogenesis of severe illness. However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC). Methods A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the pro-inflammatory cytokines/chemokines. Results Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV-2 significantly increased pro-inflammatory cytokines/chemokines and S100A9 in human primary PBMCs. Conclusion These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation., Graphical Abstract

Urinary tract infections (UTIs) are one of the most common types of bacterial infection in humans in various parts of the world and are caused mainly by uropathogenic Escherichia coli (UPEC). A total of 58 UPEC isolates from urine were characterized by serotyping and pulsed-field gel electrophoresis (PFGE). The majority of the UPEC strains belonged to serogroups O2 and O6. The UPEC strains were grouped under different pulsotypes and majority of them belonged to serogroups O2 and O6. Among the 14 virulence factors considered, 13 were present in various serogroups. The virulence genes fimH and sfa were present in all the isolates while none of the isolates carried lt-1. The strains exhibited 36 different virulence patterns, of which 11, referred to as UP (UPEC pattern) 1 to UP 11 were most common. Antibiotic resistance profiling of the UPEC isolates revealed that the serogroups O2 and O6 contain the highest number of resistant strains. The data from the current study depicting the distribution of UPEC strains among various serogroups and pulsotypes, and the occurrence of virulence genes and antibiotics resistance offer useful information on the epidemiological features of UPEC in Korea for the enhanced surveillance of potential emergence of UPEC.

Urinary tract infections (UTIs) are among the most common infections in humans, predominantly caused by uropathogenic Escherichia coli (UPEC). The diverse genomes of UPEC strains mostly impede disease prevention and control measures. In this study, we comparatively analyzed the whole genome sequence of a highly virulent UPEC strain, namely UPEC 26-1, which was isolated from urine sample of a patient suffering from UTI in Korea. Whole genome analysis showed that the genome consists of one circular chromosome of 5,329,753 bp, comprising 5064 protein-coding genes, 122 RNA genes (94 tRNA, 22 rRNA and 6 ncRNA genes), and 100 pseudogenes, with an average G+C content of 50.56%. In addition, we identified 8 prophage regions comprising 5 intact, 2 incomplete and 1 questionable ones and 63 genomic islands, suggesting the possibility of horizontal gene transfer in this strain. Comparative genome analysis of UPEC 26-1 with the UPEC strain CFT073 revealed an average nucleotide identity of 99.7%. The genome comparison with CFT073 provides major differences in the genome of UPEC 26-1 that would explain its increased virulence and biofilm formation. Nineteen of the total GIs were unique to UPEC 26-1 compared to CFT073 and nine of them harbored unique genes that are involved in virulence, multidrug resistance, biofilm formation and bacterial pathogenesis. The data from this study will assist in future studies of UPEC strains to develop effective control measures.

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

Various immunocompromised conditions increase the risk of meningitis caused by Listeria monocytogenes. However, the relative importance of these risk factors has not been well established. We determined the risk factors that predict meningitis due to L. monocytogenes compared to that caused by Streptococcus pneumoniae. A nationwide multicenter case–control study was conducted in Korea. Cases of meningitis caused by L. monocytogenes between 1998 and 2013 were included. Patients with pneumococcal meningitis were included as controls. Multivariate logistic regression analysis was used to predict the risk factors of Listeria meningitis. A total of 36 cases and 113 controls were enrolled. The most significant predictive risk factor of Listeria meningitis was a prior history of receiving immunosuppressive therapy (odds ratio 8.12, 95 % CI 2.47–26.69). Chronic liver disease was the second most important predictive risk factor (OR 5.03, 95 % CI 1.56–16.22). Delaying appropriate antibiotic therapy by more than 6 h (hazard ratio 2.78) and fatal underlying disease (hazard ratio 2.88) were associated with increased mortality. Patients with a prior history of receiving immunosuppressive therapy within 1 month and chronic liver disease have 8.1-fold and 5-fold increased risk of meningitis by L. monocytogenes compared to S. pneumoniae, respectively.

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.

Mycobacterium chelonae (Mch) is an atypical rapidly growing mycobacterium (RGM) that belongs to the M. chelonae complex, which can cause a variety of human infections. During this type of mycobacterial infection, macrophage-derived chemokines play an important role in the mediation of intracellular communication and immune surveillance by which they orchestrate cellular immunity. However, the intracellular signaling pathways involved in the macrophage-induced chemokine production during Mch infections remain unknown. Thus, the present study aimed to determine the molecular mechanisms by which Mch activates the gene expressions of chemokine (C-C motif) ligand 2 (CCL2) and CCL5 in murine bone marrow-derived macrophages (BMDMs) and in vivo mouse model. Toll-like receptor 2 (TLR2)-deficient mice showed increased bacterial burden in spleen and lung and decreased protein expression of CCL2 and CCL5 in serum. Additionally, Mch infection triggered the mRNA and protein expression of CCL2 and CCL5 in BMDMs via TLR2 and myeloid differentiation primary response gene 88 (MyD88) signaling and that it rapidly activated nuclear factor (NF)-κB signaling, which is required for the Mch-induced expressions of CCL2 and CCL5 in BMDMs. Moreover, while the innate receptor Dectin-1 was only partly involved in the Mch-induced expression of the CCL2 and CCL5 chemokines in BMDMs, the generation of intracellular reactive oxygen species (ROS) was an important contributor to these processes. Taken together, the present data indicate that the TLR2, MyD88, and NF-κB pathways, Dectin-1 signaling, and intracellular ROS generation contribute to the Mch-mediated expression of chemokine genes in BMDMs.

As the outbreak of coronavirus disease 2019 continues and the number of confirmed cases requiring isolation increases, there is a need for a safe and efficient system to assess patients' condition. We developed and evaluated a self-assessment questionnaire consisting of 23 symptoms with linear-scale scores from 0 to 10. Patients were asked to indicate their worst score for each symptom daily, and medical personnel assessed clinical improvement or deterioration based on the changes in scores. Focused communication on severity of specific symptoms was the primary advantage for the clinicians, and a thorough check for their symptoms was helpful for patients.

Stress-induced cardiomyopathy (SCMP) is characterized by transient left ventricular (LV) systolic dysfunction with regional wall motion abnormalities that do not match coronary arterial territories 1) Although this syndrome is similar to acute myocardial infarction, the diagnosis of SCMP requires the absence of obstructive coronary artery disease or acute plaque rupture 2) There are several types of SCMP: apical ballooning (typical type, about 75–80%), midventricular ballooning (about 10–20%), basal ballooning (inverted type, about 5%), and biventricular type (less than 0 5%) The estimated incidence of SCMP is about 1–2% of patients with suspected acute coronary syndrome 3)4) Because it can be caused by intensive emotional or physical stress, there can be occurrences of SCMP in patients with novel coronavirus disease-2019 (COVID-19) In one study of 1,216 COVID-19 patients, SCMP incidence was 2% (19 patients) 5) The reported in-hospital SCMP mortality is up to 5% We present 2 fatal cases of SCMP in COVID-19 patients requiring intensive care

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

We evaluated the molecular epidemiology and microbiological characteristics of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) isolates that cause bacteremia in Korean hospitals, focusing especially on ST131. Our data suggest that ST131 isolates possessed more virulence traits and showed more multidrug resistance patterns than non-ST131 isolates. Among CTX-M-15 producers, the frequency of serum resistance was significantly higher in ST131 than in non-ST131. As in other parts of the world, the ESBL-EC ST131 clone has emerged and disseminated in both community and hospital settings in Korea, including in blood isolates in patients with bacteremia.

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.

Clostridium difficile infection (CDI) is a common cause of antibiotic-associated diarrhea with an increase in severity and frequency in the recent times. CDI can be refractory and relapses, especially in the elderly or patients with significant comorbidities. Conventional treatments with antibiotics often fail to cure the infection. Even when successfully treated, recurrent infection is common. Some studies have reported that fecal transplantation may be effective and safe for the treatment of recurrent and intractable CDI. We present two CDI cases (one recurrent and one refractory) which were treated successfully by fecal transplantation using enema.

The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.

Summary Background There are no available studies on the duration and risk factors of vancomycin-resistant enterococci (VRE) carriage after hospital discharge. In this study we investigated the duration of colonization with VRE and the risk factors for prolonged carriage in the outpatient clinic after discharge from the hospital. Methods The study took place from January 2008 to September 2009. Patients were included if they were identified as persistent VRE carriers by follow-up rectal swab or stool cultures in the outpatient setting, after discharge from the hospital without clearance of VRE. The probability of culture positivity and clearance was analyzed from the discharge date. Cox regression was performed to determine the risk factors for prolonged carriage. VRE clearance was defined as VRE-negative rectal (or stool) cultures on at least three consecutive occasions a minimum of 1 week apart. Results One hundred twenty-seven patients were included in this study. Follow-up cultures were conducted for a median of 8.86 weeks (range 1–90 weeks) after hospital discharge. The median duration of culture positivity of VRE was 5.57 weeks (range 0–50.14 weeks). Ninety-six out of 127 patients (75.6%) showed the first negative culture result at a median time of 4.86 weeks (range 0–66 weeks) after discharge. Among these patients, 15 were lost to follow-up after the first negative culture and eight were lost after the second negative culture. Sixty-eight patients (53.5%) were confirmed to have clearance of VRE during follow-up in the outpatient clinic. The median time to clearance after discharge was 8.86 weeks (range 2–90 weeks). In the cleared cases, the median time to the first negative VRE culture result was 4.71 weeks (range 0–66 weeks). Ninety percent of patients showed the first negative culture result at 25 weeks and VRE clearance at 30 weeks after discharge. Surgery or antibiotic use during admission ( p =0.048 and p =0.001, respectively), dialysis ( p =0.046), and discharge to a nursing home or other health care institution ( p =0.025) were independently associated with prolonged colonization with VRE. Conclusions The median duration of VRE colonization was 5.57 weeks after hospital discharge. In the cases with clearance during follow-up, the median time to clearance after discharge was 8.86 weeks. Risk factors for prolonged carriage were surgery, antibiotic use during admission, dialysis, and discharge to a nursing home or other health care institution. Therefore, patients with these risk factors should be managed more carefully to prevent transmission of VRE in the outpatient clinic.

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.

Mycobacterium fortuitum is a rapidly growing mycobacterium that has been regarded as an etiological agent of a variety of human infections. However, little is known about the host inflammatory responses and the molecular mechanisms by which MF-induced inflammation is regulated in macrophages. In this study, we report that MF infection leads to the induction of an anti-inflammatory molecule, A20 (also known as TNFAIP3), which is essential for the regulation of MF-induced inflammatory responses in murine bone marrow-derived macrophages (BMDMs). MF triggered the expression of tumor necrosis factor-α and interleukin-6 in BMDMs through signaling of the Toll-like receptor 2 (TLR2)-myeloid differentiation primary response gene 88. Additionally, MF rapidly induced the expression of A20, which inhibited proinflammatory cytokine expression and nuclear factor (NF)-κB reporter gene activities in BMDMs. Notably, MF-induced activation of NF-κB signaling was required for A20 expression and proinflammatory responses in BMDMs. Furthermore, the rough morphotype of the MF clinical strain induced a higher level of proinflammatory signaling activation, but less A20 induction in BMDMs, compared to the smooth morphotype. Taken together, these results suggest that MF-induced activation of host proinflammatory responses is negatively regulated through TLR2-dependent A20 expression.

Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3′-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages. Mtb infection downregulated, whereas the autophagy activators upregulated, DRAM2 expression in human monocytes and macrophages by activating AMP-activated protein kinase. In addition, overexpression of MIR144* decreased DRAM2 expression and formation of autophagosomes in human monocytes, whereas inhibition of MIR144* had the opposite effect. Moreover, the levels of MIR144* were elevated, whereas DRAM2 levels were reduced, in human peripheral blood cells and tissues in TB patients, indicating the clinical significance of MIR144* and DRAM2 in human TB. Notably, DRAM2 interacted with BECN1 and UVRAG, essential components of the autophagic machinery, leading to displacement of RUBCN from the BECN1 complex and enhancement of Ptdlns3K activity. Furthermore, MIR144* and DRAM2 were critically involved in phagosomal maturation and enhanced antimicrobial effects against Mtb. Our findings identify a previously unrecognized role of human MIR144* in the inhibition of antibacterial autophagy and the innate host immune response to Mtb. Additionally, these data reveal that DRAM2 is a key coordinator of autophagy activation that enhances antimicrobial activity against Mtb.

The first cases of infective endocarditis due to a new species of Bergeyella , Bergeyella cardium sp. nov., are reported. Two strains, 13-07 T (= JCM 30115 T = NCCP 15908 T ) and 13-16, were independently isolated from 2 patients in different hospitals in Korea. Initially, the isolates were identified as Brevundimonas spp.; however, their 16S rRNA gene sequences shared a similarity of 94.9% with Bergeyella zoohelcum , implying that they are a new species belonging to of the genus Bergeyella . The organisms might be susceptible to many commonly used antibiotics, including penicillin. The first case was successfully treated with ceftriaxone, and the second, with piperacillin/tazobactam plus amikacin.

Background From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. Materials and Methods We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. Results The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. Conclusion The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.