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 multidrugresistant 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.

Experimental and Mathematical Optimization of a Pooling Test for Detection of SARS-CoV-2 in a Population with Low Viral Load

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.

Experimental and Mathematical Optimization of a Pooling Test for Detection of SARS-CoV-2 in a Population with Low Viral Load

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.

Higher Risk for All-cause Mortality of Staphylococcus aureus Bacteremia in Patients with Non-Dialysis Dependent Chronic Kidney Disease

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 nonCKD (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 <48 h was independently related to improved survival following SAB among ND-CKD (adjusted HR, 0.304; 95% CI, 0,108 – 0.857; P = 0.024) and dialysis (adjusted HR, 0.323; 95% CI, 0,116 – 0.897; P = 0.030) patients. @*Conclusion@#ND-CKD patients demonstrated poor outcome following SAB and administration of appropriate antibiotics within 48 h could reduce the risk for mortality.

Self-Assessment Questionnaire for Efficient and Safe Evaluation of Patients with Mild COVID-19

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.

COVID-19 Patients Upregulate Toll-like Receptor 4-mediated Inflammatory Signaling That Mimics Bacterial Sepsis

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 (SARSCoV-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 proinflammatory 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-CoV2 significantly increased proinflammatory 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.

Acute Kidney Injury and Kidney Damage in COVID-19 Patients

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.

The Usefulness of Hematological Parameters for Assessing Disease Progression in Patients with HIV Infection

BACKGROUND: In patients with HIV, CD4+ T cell count and viral load are the main laboratory tests performed to assess clinical management. However, they require extensive resources. In this study, we aimed to determine whether hematological parameters measured using a hematology analyzer are useful as surrogate markers of CD4+ T cell count and viral load in HIV-infected patients. METHODS: Peripheral blood samples were obtained from 14 HIV-naïve, 105 HIV-treated, and 103 uninfected individuals. Hematological parameters were measured using the ADVIA 2120i hematology analyzer (Siemens Healthcare Diagnostics, USA). RESULTS: In HIV-naïve and -treated patients, the percentage of large unstained cells (%LUCs) was 2.5±1.6% and 1.9±0.7%, respectively, compared to 1.6±0.5% in HIV-uninfected controls. The %LUCs was higher in HIV patients with low CD4⁺ T cell count below 200/μL (2.4±1.0%) or high viral load ≥200 copies/mL (2.4±0.8%) than in other infected groups. Significant differences in lymphocyte count were observed between the HIV-naïve (1.5±0.6×10⁹/L) and uninfected (2.0±0.6×10⁹/L) groups as well as between HIV patients with CD4⁺ T cells ≥500/μL (2.5±0.6×10⁹/L) and other infected groups. Neutrophil count varied between high viral load (3.0±1.4×10⁹/L) and low viral load (3.7±1.3×10⁹/L) groups. The CD4⁺ T cell count correlated with lymphocyte count (r=0.642, P<0.0001) and %LUCs (r=-0.287, P=0.002). CONCLUSIONS: %LUCs, lymphocyte count, and neutrophil count are probable surrogate markers of CD4⁺ T cells and viral load.

Vertebral Osteomyelitis due to Mycobacterium intracellulare in an Immunocompetent Elderly Patient After Vertebroplasty

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 cervical 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.

Subdural Empyema Caused by Nontyphoidal Salmonella in a Patient with a Previous Evacuation of Subdural Hematoma / 대한내과학회지

Nontyphoidal Salmonella infection often results in acute gastroenteritis, but extraintestinal infection presenting as a subdural empyema is unusual. We report a case of a 67-year-old man diagnosed with a subdural empyema caused by Salmonella group B that developed after evacuation of a subdural hematoma. To our knowledge, this is the first such case report in Korea.

Outbreaks of Middle East Respiratory Syndrome in Two Hospitals Initiated by a Single Patient in Daejeon, South Korea

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.

Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea

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.

Septic Knee Arthritis Caused by Staphylococcus lugdunensis After Intraarticular Injection Therapy

Staphylococcus lugdunensis is a coagulase-negative staphylococcus. However, it causes various clinically important human infections and behaves similar to Staphylococcus aureus. S. lugdunensis reportedly causes infective endocarditis, skin and soft tissue infection, bone and joint infection, septicemia, endarteritis, urinary tract infection, ocular infection, and peritonitis. There are no reports of septic arthritis by this organism in Korea. We presented a case of septic arthritis due to S. lugdunensis in an elderly patient with diabetes mellitus after an intra-articular injection.

Vertebral Osteomyelitis caused by Burkholderia cepacia in an Immunocompetent Elderly Patient After Acupuncture

Burkholderia cepacia is an important nosocomial pathogen in hospitalized patients, particularly those with prior antimicrobial therapy. B. cepacia causes various clinically significant infections such as bacteremia, pneumonia, and urinary tract and surgical site infections. However, osteomyelitis caused by B. cepacia is very rare. We present a case of B. cepacia vertebral osteomyelitis with review of the literature.

Diagnosis of scrub typhus: introduction of the immunochromatographic test in Korea

No abstract available.

Successful Control of Extended-spectrum Beta-lactamase-producing Klebsiella pneumoniae Outbreak in a Neonatal Intensive Care Unit / 병원감염관리

BACKGROUND: Extended-spectrum beta-lactamase-producing (ESBL) Klebsiella pneumoniae is an important cause of nosocomial infections in neonatal intensive care units (NICUs). This study aimed to reduce ESBL-producing K. pneumoniae in the NICU by using infection control measures. METHODS: We performed prospective surveillance cultures, monitoring, and education for infection control in the NICU between May and August 2011. Specimens were collected from all infants and the environment including stethoscopes, thermometers, ventilators, incubators, etc. The anterior nares and hands of healthcare workers were also screened. We inspected infection control practices and provided feedback. The level of infection control awareness was measured using a questionnaire. RESULTS: The level of awareness and performance of hand washing increased significantly after intervention (both P<0.001). The environmental management of healthcare providers also improved significantly (P=0.001). The yield of ESBL-producing K. pneumoniae from clinical specimens decreased gradually throughout the study period (30.4% in May to 12.6% in August). Central catheter-related K. pneumoniae bacteremia decreased from 1.3/1000 to 0/1000 catheter-days. CONCLUSION: Infection control measures including education, monitoring, and surveillance can lower the incidence of ESBL-producing K. pneumoniae in the NICU.

A Case of Thymoma with Immunodeficiency (Good's Syndrome) with Disseminated Tuberculosis / 대한내과학회지

Good's syndrome is the rare association of immunodeficiency with thymoma, characterized by hypogammaglobulinemia, depleted B-cells, diminished T-cells and inversion of the CD4/CD8 ratio. Thymectomy does not usually improve hypogammaglobulinemia; thus, the patient remains prone to infections. Infections affect primarily the sinopulmonary and gastrointestinal system. Here we present a case of a 71-year-old woman with common manifestations of Good's syndrome who succumbed to disseminated tuberculosis. Serum immunoglobulin levels should be measured for patients with thymoma and susceptibility to infection.

Mortality of Community-Acquired Pneumonia in Korea: Assessed with the Pneumonia Severity Index and the CURB-65 Score

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.

Successful Fecal Transplantation by Enema for Recurrent and Refractory Clostridium difficile Infection

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.

A Case of Vertebral Osteomyelitis Caused by Serratia grimesii in a Patient without Predisposing Factors / 대한내과학회지

Vertebral osteomyelitis or paraspinal abscess caused by Serratia species is rare and has been reported only in certain groups of people, such as intravenous drug users, immunocompromised hosts, and patients who have undergone invasive procedures. However, we report here that Serratia was recovered from a patient with vertebral osteomyelitis and epidural abscess without predisposing factors. The organism was initially identified as Serratia liquefaciens by a Vitek II-based assessment. It was finally identified as Serratia grimesii by 16S rRNA gene sequence analysis. We present the first case of vertebral osteomyelitis caused by S. grimesii in a patient without risk factors and who was managed successfully.