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

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

Correlates of burnout among healthcare workers during the COVID-19 pandemic in South Korea.

Burnout is a form of negative emotional and physical response to job stress. This study aimed to investigate the prevalence of burnout among healthcare workers responding to the coronavirus disease 2019 (COVID-19) outbreak in Korea and to explore correlates of burnout among healthcare workers. A nationwide questionnaire-based survey was conducted from December 1, 2020, to January 29, 2021 on 1425 healthcare workers who worked in one of the 16 healthcare facilities designated for COVID-19 care, in public health centers, or as paramedics in Korea. Burnout was assessed using 16 Korean-adapted items based on the Oldenburg Burnout Inventory (OLBI). Data were collected using a structured questionnaire and analyzed using the R version 4.1.1 software program. OLBI results indicate clinically exhaustion in 84.5% (1204/1425) and clinically disengagement in 91.1% (1298/1425), and 77.3% (1102/1425) met the score criteria for both the exhaustion and disengagement subscales for burnout. Burnout rate was significantly increased in the group with chronic fatigue symptoms (Fatigue Severity Scale ≥ 3.22) after the outbreak of COVID-19 (OR, 3.94; 95% CI 2.80-5.56), in the female group (OR, 2.05; 95% CI 1.46-2.86), in the group with physical symptoms (Patient Health Questionnaire-15 ≥ 10) after the outbreak of COVID-19 (OR, 2.03; 95% CI 1.14-3.60), in the group with a higher Global Assessment of Recent Stress scale (OR, 1.71; 95% CI 1.46-2.01), in the group with post-traumatic stress symptoms (Primary Care Post-Traumatic Stress Disorder-5 ≥ 2) (OR, 1.47; 95% CI 1.08-2.01), and in the younger age group(OR, 1.45; 95% CI 1.22-1.72). The chronic fatigue symptoms were correlated with cumulative days of care (OR, 1.18; 95% CI 1.02-1.37). The physical symptoms were correlated with average contact hours with COVID-19 patients per day (OR, 1.34; 95% CI 1.17-1.54), and cumulative days of care (OR, 1.21; 95% CI 1.06-1.38). Most Korean healthcare workers suffered from burnout related to excessive workload during the COVID-19 pandemic. During a widespread health crisis like COVID-19, it is necessary to regularly check the burnout status in healthcare workers and reduce their excessive workload by supplementing the workforce and providing appropriate working hours sufficient rest hours.

Usefulness analysis of the 2018 ASCO/IDSA guideline for outpatient management of fever and neutropenia in adults treated for malignancy.

Although the clinical practice guideline for outpatient management of febrile neutropenia (FN) in adults treated for malignancy was updated by the ASCO/IDSA in 2018, most patients with FN in our hospital have been hospitalized. We performed this study to analyze the usefulness of the guideline. The medical records of patients hospitalized for FN in Kyungpook National University Chilgok Hospital from May 2016 to April 2018 were retrospectively reviewed. The feasibility of candidates for outpatient management according to the guideline was evaluated based on the outcomes. A total of 114 patients were enrolled and categorized into two groups, low-risk (38.6%) and high-risk (61.4%). The proportion of feasible candidates for outpatient management was 70.2% and was higher in the low-risk than in the high-risk group (90.0% vs. 57.1%; P < 0.001). The low-risk group had no mortality, no resistance to oral amoxicillin/clavulanate or ciprofloxacin, a higher rate of successful empirical antibiotics, and lower rates of glycopeptide or carbapenem administration. A significant number of hospitalized cancer patients treated for FN after chemotherapy were found to be feasible candidates for outpatient management. The guideline can be a useful tool to reduce labor of healthcare workers and hospitalization costs.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Trends of Cause of Death among Human Immunodeficiency Virus Patients and the Impact of Low CD4 Counts on Diagnosis to Death: a Retrospective Cohort Study.

BACKGROUND: Monitoring the full spectrum of causes of death among human immunodeficiency virus (HIV) patients has become increasingly important as survival improves because of highly active antiretroviral therapy. However, there are no recently published data regarding the changes in the causes of death among HIV patients based on year of HIV diagnosis, and the impact of low CD4 count at the time of HIV diagnosis on the clinical outcome is still unclear in Korea. METHODS: A retrospective cohort study was conducted with 801 patients with HIV infection who were followed up at a tertiary university hospital and diagnosed with HIV between July 1984 and October 2019. The causes of death were analyzed by descriptive analysis based on CD4 count and the year of HIV diagnosis. Kaplan-Meier and log rank tests were performed to compare the prognosis between the CD4 < 200 cells/mm³ and CD4 ≥ 200 cells/mm³ groups. RESULTS: Among 801 patients, 67 patients were eligible for the death cause analysis. Infection-related death accounted for 44 patients (65.7%) and non-infection related death accounted for 23 patients (32.4%). Pneumocystis pneumonia (29.9%) was the single most common cause of death in both past and present cases, and tuberculosis (19.4%) was the second leading cause of death from infections, but the frequency has declined in recent years. Causes of infection-related death have decreased, whereas non-infection related causes of death have increased remarkably. Malignancy-related death was the most common cause of non-infection related death. Acquired immunodeficiency syndrome (AIDS) non-related malignancy accounted for 11.9%, whereas AIDS-related malignancy accounted for 6.0% of the total death among HIV patients. No significant statistical differences were found in mortality rate (P = 0.228), causes of death (P = 0.771), or survival analysis (P = 0.089) between the CD4 < 200 cells/mm³ and CD4 ≥ 200 cells/mm³ groups. CONCLUSION: Being diagnosed with CD4 < 200 cells/mm³ at the time of HIV diagnosis was not an indicator of greater risk of death compared with the CD4 ≥ 200 cells/mm³ group. Malignant tumors have become an important cause of death in recent years, and an increasing tendency of AIDS-non-related malignancy causes has been observed.

Significance of Increased Rapid Treatment from HIV Diagnosis to the First Antiretroviral Therapy in the Recent 20 Years and Its Implications: the Korea HIV/AIDS Cohort Study.

From December 2006 to December 2016, 1,429 patients enrolled in the Korea human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) Cohort Study were investigated. Based on the year of diagnosis, the time interval between HIV diagnosis and initiation of antiretroviral therapy (ART) was analyzed by dividing it into 2 years. The more recent the diagnosis, the more likely rapid treatment was initiated (P < 0.001) and the proportion of patients starting ART on the same day of HIV diagnosis was increased in 2016 (6.5%) compared to that in 2006 (1.7%). No significant difference in the median values of CD4+ cell counts according to the diagnosis year was observed. In the past 20 years, the time from the HIV diagnosis to the initiation of ART was significantly reduced. Rapid treatment was being implemented at the HIV diagnosis, regardless of CD4+ cell count. Considering the perspective "treatment is prevention," access to more rapid treatment is necessary at the time of HIV diagnosis.

Testican-1, as a novel diagnosis of sepsis.

The development of new sepsis-specific biomarkers is mandatory to improve the detection and monitoring of the disease. Testican-1 is a highly conserved, multidomain proteoglycan that is most prominently expressed in the thalamus of the brain, and is upregulated in activated astroglial cells of the cerebrum. The aim of this study was to evaluate blood levels of Testican-1 in septic patients. A prospective study of 82 patients with sepsis was conducted. Furthermore, C57BL/6 mice were administrated with lipopolysaccharide (LPS), high mobility group box 1 (HMGB1) protein or subjected to cecal ligation and puncture (CLP) surgery. Alternatively, human umbilical vein endothelial cells (HUVECs) or C57BL/6 mice were exposed to LPS (100 ng/mL) or HMGB1 (1 µg/mL). LPS, HMGB1, or CLP enhanced the synthesis and secretion of Testican-1 in HUVECs and mice. In patients admitted to the intensive care unit (ICU) with sepsis, circulating levels of Testican-1 were significantly high (sepsis, 20.44-63.37 ng/mL, n = 30; severe sepsis, 41.30-98.69 ng/mL, n = 22; septic shock, 98.10-151.85 ng/mL, n = 30) when compared to the levels of control donors (6.97-8.77 ng/mL, n = 21), reflecting the severity of the disease. These results suggest that in septic patients, Testican-1 blood level is related to the severity of sepsis and Testican-1 could be used as a biomarker to determine the severity of sepsis.

Association between Type A blaZ Gene Polymorphism and Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus.

Some proportion of type A blaZ gene-positive methicillin-susceptible Staphylococcus aureus strains exhibit the cefazolin inoculum effect (CIE). The type A blaZ gene was divided into two groups by single nucleotide polymorphisms (SNPs) at Ser226Pro and Cys229Tyr. The median cefazolin MICs at a high inoculum concentration were 5.69 µg/ml for the Ser-Cys group and 40.32 µg/ml for the Pro-Tyr group (P = 0.01). The SNPs at codons 226 and 229 in the amino acid sequence encoded by the blaZ gene were closely associated with the CIE.

The acceptable duration between occupational exposure to hepatitis B virus and hepatitis B immunoglobulin injection: Results from a Korean nationwide, multicenter study.

BACKGROUND: Postexposure prophylaxis for occupational exposure to hepatitis B virus (HBV) plays an important role in the prevention of HBV infections in health care workers (HCWs). We examined data concerning the acceptable duration between occupational exposure and administration of a hepatitis B immunoglobulin (HBIG) injection in an occupational clinical setting. METHODS: A retrospective analysis was conducted with data from 143 cases of HCWs exposed to HBV in 15 secondary and tertiary teaching hospitals between January 2005 and June 2013. Data were taken from the infection control records of each hospital. RESULTS: Active vaccination after HBV exposure was started in 119 cases (83.2%) and postvaccination testing for hepatitis B antibody showed positive seroconversion in 93% of cases. In 98 cases (68.5%), HBIG was administered within 24 hours after HBV exposure; however, 45 HCWs (31.5%) received an HBIG injection more than 24 hours postexposure and 2 among the 45 received an injection after 7 days. Although 31.5% received an HBIG injection more than 24 hours postexposure, no cases of seroconversion to hepatitis b antibody positivity occurred. CONCLUSIONS: For susceptible HCWs, HBIG administered between 24 hours and 7 days postexposure may be as effective as administration within 24 hours in preventing occupational HBV infection.

Impact of first-line antifungal agents on the outcomes and costs of candidemia.

Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia.

Risk factors and pathogenic significance of severe sepsis and septic shock in 2286 patients with gram-negative bacteremia.

BACKGROUND: The aim of this study was to identify risk factors for development of severe sepsis or septic shock and to evaluate the clinical impact of severe sepsis on outcome in patients with gram-negative bacteremia (GNB). METHODS: From the database of a nationwide surveillance for bacteremia, patients with GNB were analyzed. Data of patients with severe sepsis or septic shock were compared with those of patient with sepsis. RESULTS: Of 2286 patients with GNB, 506 (22.1%) fulfilled the criteria of severe sepsis or septic shock. Factors associated with severe sepsis or septic shock in the multivariate analysis included renal disease, indwelling urinary catheter, hematologic malignancy, and neutropenia. The 30-day mortality of patients with severe sepsis or septic shock was significantly higher than that of patients with sepsis (39.5% [172/435] vs. 7.4% [86/1170]; P < 0.001). Multivariable analysis revealed that solid tumor, liver disease, pulmonary disease, pneumonia, and pathogens other than Escherichia coli, which were risk factors of development of severe sepsis or septic shock, were also found to be strong predictors of mortality. Severe sepsis or septic shock was a significant factor associated with mortality (OR, 3.34; 95% CI, 2.35-4.74), after adjustment for other variables predicting poor prognosis. CONCLUSIONS: Severe sepsis or septic shock was a common finding in patients with GNB, predicting a higher mortality rate. Renal disease and indwelling urinary catheter were the most important risk factors significantly associated with severe sepsis or septic shock among patients with GNB.

Clinical impact of methicillin resistance on outcome of patients with Staphylococcus aureus infection: a stratified analysis according to underlying diseases and sites of infection in a large prospective cohort.

OBJECTIVE: This study was conducted to identify the predictors of mortality and to evaluate the impact of methicillin resistance on outcome in patients with Staphylococcus aureus infection according to underlying conditions and type of infection. METHODS: An observational cohort study including 4949 patients with S. aureus infection was conducted. We compared data from patients with MRSA infection with those with MSSA infection. RESULTS: The 30-day mortality rate of MRSA group was significantly higher than that of MSSA group (15.6% vs. 6.2%, P < 0.001). However, MRSA infection was not found to be independent risk factor for mortality after adjusting for other variables (OR = 1.03, 95% CI = 0.80-1.32). When we analyzed patients with S. aureus bacteremia (n = 709), MRSA infection was found to be significantly associated with mortality in multivariate analysis (Adjusted OR = 1.69, 95% CI = 1.15-2.49). When the 30-day mortality rates were compared according to underlying diseases, the 30-day mortality rate of MRSA group was significantly higher than that of MSSA group in patients with malignancy or renal diseases. MRSA infection was also found to be one of the independent risk factors for mortality in patients with malignancy (adjusted OR = 1.69, 95% CI = 1.06-2.70) and in those with renal disease (adjusted OR = 1.70, 95% CI = 1.0-2.89), after adjustment for host variables. CONCLUSIONS: Methicillin resistance adversely affected the outcome of patients with S. aureus infection, in patients with cancer or renal disease and in those with S. aureus bacteremia, although MRSA infection was not found to be significantly associated with higher mortality in overall patient population.

Epidemiology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a prospective study by the Asian network for surveillance of resistant pathogens.

Appropriate antimicrobial treatment of community-acquired pneumonia (CAP) should be based on the distribution of aetiological pathogens, antimicrobial resistance of major pathogens, clinical characteristics and outcomes. We performed a prospective observational study of 955 cases of adult CAP in 14 hospitals in eight Asian countries. Microbiological evaluation to determine etiological pathogens as well as clinical evaluation was performed. Bronchopulmonary disease (29.9%) was the most frequent underlying disease, followed by cardiovascular diseases (19.9%), malignancy (11.7%) and neurological disorder (8.2%). Streptococcus pneumoniae (29.2%) was the most common isolate, followed by Klebsiella pneumoniae (15.4%) and Haemophilus influenzae (15.1%). Serological tests were positive for Mycoplasma pneumoniae (11.0%) and Chlamydia pneumoniae (13.4%). Only 1.1% was positive for Legionella pneumophila by urinary antigen test. Of the pneumococcal isolates, 56.1% were resistant to erythromycin and 52.6% were not susceptible to penicillin. Seventeen percent of CAP had mixed infection, especially S. pneumoniae with C. pneumoniae. The overall mortality rate was 7.3%, and nursing home residence, mechanical ventilation, malignancy, cardiovascular diseases, respiratory rate>30/min and hyponatraemia were significant independent risk factors for mortality by multivariate analysis (P<0.05). The current data provide relevant information about pathogen distribution and antimicrobial resistance of major pathogens of CAP as well as clinical outcomes of illness in Asian countries.

Risk factors for specific methicillin-resistant Staphylococcus aureus clones in a Korean hospital.

OBJECTIVES: To analyse the risk factors for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections caused by different clonal types. METHODS: A total of 134 non-duplicate nosocomial MRSA isolates were analysed for clonal types by molecular typing techniques. The medical records of 90 patients who had documented MRSA infection were evaluated retrospectively. RESULTS: Two predominant MRSA clones of sequence types (STs) ST239 (n = 75) and ST5 (n = 39) accounted for 85% of the isolates. Management of patients in the departments of orthopaedic surgery, neurosurgery and plastic surgery was identified as a risk factor for infection with MRSA of ST239, while the presence of intravascular catheters was a risk factor for infection with ST5. Pulmonary infection was significantly higher in the patients infected with ST239 strains than in the patients infected with ST5 strains (P < 0.05). The overall mean duration of antimicrobial therapy for the patients with ST239 infection was significantly more than that for the patients with ST5 infection (P < 0.05). CONCLUSIONS: ST239 and ST5 were the predominant MRSA clones in the study hospital. Risk factors were significantly different between ST239 and ST5 strains. The results of this study will be of use in designing larger prospective epidemiological studies for MRSA infection based on clonal types.