Showing papers in "Infection and Chemotherapy in 2021"
30 citations
TL;DR: The guidelines were developed as a part of the 2021 Academic R&D Service Project of the Korea Disease Control and Prevention Agency in response to requests from healthcare professionals in clinical practice for guidance on developing antimicrobial stewardship programs as discussed by the authors.
Abstract: These guidelines were developed as a part of the 2021 Academic R&D Service Project of the Korea Disease Control and Prevention Agency in response to requests from healthcare professionals in clinical practice for guidance on developing antimicrobial stewardship programs (ASPs). These guidelines were developed by means of a systematic literature review and a summary of recent literature, in which evidence-based intervention methods were used to address key questions about the appropriate use of antimicrobial agents and ASP expansion. These guidelines also provide evidence of the effectiveness of ASPs and describe intervention methods applicable in Korea.
24 citations
TL;DR: In this article, an online survey and statistical analysis were conducted by Kyungpook National University Hospital on 5,252 patients diagnosed as COVID-19 between February 18, 2020 and March 14, 2020.
Abstract: BACKGROUND: As the coronavirus disease 2019 (COVID-19) pandemic has progressed, there has been a growing awareness of the long-term impacts of the COVID-19 infection. However, until recently, there was no published study that investigated COVID-19-related sequelae and related factors for greater than six months from the onset of COVID-19 symptoms or the time of COVID-19 diagnosis in Korea. MATERIALS AND METHODS: Online survey and statistical analysis were conducted by Kyungpook National University Hospital on 5,252 patients diagnosed as COVID-19 between February 18, 2020 and March 14, 2020. Responders aged between 16 and 70 years were included. Long-term sequelae were defined as persistent symptoms or signs ≥ 6 months after acute COVID-19 infection. The survey was conducted from September 8, 2020 to September 10, 2020. Clinical characteristics and self-reported clinical sequelae of the responders were analyzed to investigate the prevalence and factors associated with sequelae using descriptive and multivariate logistic regression analysis. RESULTS: The median period from the date of the first symptom onset or COVID-19 diagnosis to the time of the survey was 195 (interquartile range [IQR] 191 - 200) days. The response rate was 17.1% (900 out of 5,252). The median age was 31 (IQR 24.0 - 47.0) years old, and 627 responders were female (69.7%). Regarding the disease severity, 29 (3.2%) were asymptomatic, 763 (84.8%) mild, 86 (9.6%) moderate, 17 (1.9%) severe, and 5 (0.6%) critical. In total, 591 (65.7%) responders suffered from COVID-19-related long-term sequelae and 78 (8.6%) responders were receiving outpatient treatment for COVID-19-related long-term sequelae. The most common symptoms identified during the isolation period were anosmia and ageusia at 44.5% and 43.5%, respectively. Fatigue was the most common long-term sequelae, accounting for 253 (26.2%) responders, followed by concentration difficulty, amnesia, cognitive dysfunction, anxiety, and depression, which accounted for over 20%. Female gender was identified as the factor associated with mental and psychological long-term sequelae (P <0.05). CONCLUSION: The results showed that the rate of COVID-19-related long-term sequelae was 65.7%. The most common long-term sequela was fatigue. The risk factor identified was female gender. It was found that the long-term sequelae had various manifestations, including mental and psychological aspects. To improve the care of COVID-19 recovered patients with COVID-19-related long-term sequelae, the participation of a comprehensive and an interdisciplinary group of researchers is required.
20 citations
TL;DR: In this article, the authors provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence and provide guidelines for the treatment of coronavirus disease 2019 (COVID-2019) pandemic.
Abstract: Despite the global effort to mitigate the spread, coronavirus disease 2019 (COVID-19) has become a pandemic that took more than 2 million lives There are numerous ongoing clinical studies aiming to find treatment options and many are being published daily Some effective treatment options, albeit of variable efficacy, have been discovered Therefore, it is necessary to develop an evidence-based methodology, to continuously check for new evidence, and to update recommendations accordingly Here we provide guidelines on pharmaceutical treatment for COVID-19 based on the latest evidence
20 citations
TL;DR: In this paper, the authors conducted a systematic review on the prioritization of the COVID-19 vaccine and found that older adults were the most frequently mentioned group, and healthcare workers (HCWs) were the 1st priority group.
Abstract: BACKGROUND: Since the supply of coronavirus disease 2019 (COVID-19) vaccines will be limited worldwide, it is essential to prioritize vaccination based on scientific evidence. Although several frameworks and studies on vaccine distribution have been published, no published systematic review has evaluated the prioritization of the COVID-19 vaccine. MATERIALS AND METHODS: We searched 4 different databases, PubMed, SCOPUS, Web of Science, and EMBASE for articles published between January 2019 and December 31, 2020. Studies were included if they contained the primary search terms "vaccine", "COVID-19", and "prioritization". In addition, we manually included reports from national and international websites. RESULTS: Thirteen studies met the inclusion criteria. In these studies, older adults were the most frequently mentioned group, and healthcare workers (HCWs) were mentioned as the 1st priority group. HCWs and patients with comorbidities were the 2nd and 3rd most frequently mentioned groups in the reviewed papers. Reducing severe COVID-19 was the most frequently mentioned goal. CONCLUSION: Since vaccination programs have been initiated in several countries, scientific evidence on vaccination prioritization is needed to increase our knowledge of general vaccine prioritization and improve vaccine acceptance. Our results showed that HCWs and older adults were the most frequently valued in studies.
18 citations
TL;DR: In this article, the efficacy and safety of Interferon Beta (IFN-s) in patients who have a confirmed COVID-19 diagnosis was reviewed. And the authors found that patients who received early treatment with IFN-S experienced significantly reduced length of hospitalization, mortality, ICU admission, and mechanical ventilation.
Abstract: BACKGROUND: The high rate of transmission and infection of coronavirus disease 2019 (COVID-19) is a public health emergency of major epidemiological concern. No definitive treatments have been established, and vaccinations have only recently begun. We aim to review the efficacy and safety of Interferon Beta (IFN-s) in patients who have a confirmed COVID-19 diagnosis. MATERIALS AND METHODS: A search from PubMed, Science Direct, Cochrane, and Clinicaltrials.gov databases were conducted from December 2019 to December 2020 to review the efficacy and safety of IFN-s in adult patients with COVID-19 confirmed. We included randomized controlled trials, case reports, and experimental studies. Correspondences, letters, editorials, reviews, commentaries, case control, cross-sectional, and cohort studies that did not include any new clinical data were excluded. RESULTS: Of the 66 searched studies, 8 were included in our review. These studies demonstrated that although IFN-s did not reduce the time to clinical response, there was an increase in discharge rate at day 14 and a decrease in mortality at day 28. The time to negative reverse transcription polymerase chain reaction (RT-PCR) was shown to be significantly shortened in patients receiving IFN-s, along with a lower nasopharyngeal viral load. Further, patients receiving IFN-s had a less significant rise in IL-6. IFN-s was shown to decrease intensive care unit (ICU) admission rate, the requirement of invasive ventilation in severe cases, and improve the survival rate compared to control groups. There were no severe adverse events reported. Our review found that patients who received early treatment with IFN-s experienced significantly reduced length of hospitalization, mortality, ICU admission, and mechanical ventilation. A greater chance of clinical improvement and improved imaging studies was noted in patients who received IFN-s. There were no reported deaths associated with the addition of IFN-s. Further randomized trials involving more significant sample sizes are needed to better understand the effect of IFN-s on survival in COVID-19. CONCLUSION: This review identified encouraging data and outcomes of incorporating IFN-s to treat COVID-19 patients. IFN-s has been shown to decrease hospital stay's overall length and decrease the severity of respiratory symptoms when added to the standard of care. Also, in some studies, it has been demonstrated to reduce the length of ICU stay, enhance survival rate, and decrease the need for invasive mechanical ventilation. There were minor side effects reported (neuropsychiatric symptoms and hypersensitivity reaction). However, randomized clinical trials with a large sample size are needed to assess IFN-s's benefit precisely.
17 citations
TL;DR: In this paper, the ability of chest computed tomography (CT) severity score (CSS) to predict ICU admission and mortality in patients with COVID-19 pneumonia was assessed with the area under the receiver operating characteristic (ROC) curves.
Abstract: Background The novel coronavirus disease 2019 (COVID-19) continues to wreak havoc worldwide. This study assessed the ability of chest computed tomography (CT) severity score (CSS) to predict intensive care unit (ICU) admission and mortality in patients with COVID-19 pneumonia. Materials and methods A total of 192 consecutive patients with COVID-19 pneumonia aged more than 20 years and typical CT findings and reverse-transcription polymerase chain reaction positive admitted in a tertiary hospital were included. Clinical symptoms at admission and short-term outcome were obtained. A semi-quantitative scoring system was used to evaluate the parenchymal involvement. The association between CSS, disease severity, and outcomes were evaluated. Prediction of CSS was assessed with the area under the receiver-operating characteristic (ROC) curves. Results The incidence of admission to ICU was 22.8% in men and 14.1% in women. CSS was related to ICU admission and mortality. Areas under the ROC curves were 0.764 for total CSS. Using a stepwise binary logistic regression model, gender, age, oxygen saturation, and CSS had a significant independent relationship with ICU admission and death. Patients with CSS ≥12.5 had about four-time risk of ICU admission and death (odds ratio 1.66, 95% confidence interval 1.66 - 9.25). The multivariate regression analysis showed the superiority of CSS over other clinical information and co-morbidities. Conclusion CSS was a strong predictor of progression to ICU admission and death and there was a substantial role of non-contrast chest CT imaging in the presence of typical features for COVID-19 pneumonia as a reliable predictor of clinical severity and patient's outcome.
15 citations
TL;DR: In this article, the authors compared the contribution of comorbidities in the development of critical conditions in coronavirus disease 2019 (COVID-19) patients by conducting a metaanalysis and network meta-analysis of 18 studies.
Abstract: Severe illness and poor outcome are mainly associated with aging or certain medical comorbidities, especially chronic diseases. However, factors for unfavorable prognosis have not been well described owing to relatively small sample sizes and single-center reports. Therefore, this study aimed to compare the contribution of comorbidities in the development of critical conditions in coronavirus disease 2019 (COVID-19) patients. Pooled estimates of relative risks (RRs) and their 95% confidence intervals (CIs) were calculated by conducting a meta-analysis and network meta-analysis of 18 studies. Chronic obstructive pulmonary disease (COPD) was most strongly associated with the overall critical condition (RR = 4.22, 95% CI = 3.12 - 5.69), followed by cardiovascular disease (CVD) (RR = 3.00, 95% CI = 2.41 - 3.73), malignancy (RR = 2.91, 95% CI = 2.16 - 3.91), cerebrovascular accident (CVA) (RR = 2.86, 95% CI = 1.95 - 4.19), diabetes (RR = 2.10, 95% CI = 2.16 - 3.91), hypertension (RR = 2.02, 95% CI = 1.82 - 2.23), and chronic kidney disease (RR = 2.00, 95% CI = 1.36 - 2.94). The presence of comorbidities except for chronic liver disease and chronic kidney disease significantly increased the risk of severe infection, intensive care unit (ICU) admission, and cardiac injury in the subgroup analysis by types of critical conditions. Preexisting hypertension and diabetes additionally increased the risk of acute respiratory distress syndrome (ARDS). Among comorbidities, COPD had the highest probability of leading to severe COVID-19, ICU admission, and liver injury, while malignancy was most likely to cause ARDS and cardiac injury. In summary, preexisting COPD, CVD, CVA, hypertension, diabetes, and malignancy are more likely to worsen the progression of COVID-19, with severe infection, ICU admission requirement, and cardiac injury development.
15 citations
TL;DR: Transmission of SARS-CoV-2 in the hematologic ward occurred rapidly in the multi-patient room and shared bathroom settings and there was a case of possible airborne transmission due to unexpected airflow.
Abstract: BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks occur in hospitals in many parts of the world. In hospital settings, the possibility of airborne transmission needs to be investigated thoroughly. MATERIALS AND METHODS: There was a nosocomial outbreak of COVID-19 in a hematologic ward in a tertiary hospital, Seoul, Korea. We found 11 patients and guardians with COVID-19 through vigorous contact tracing and closed-circuit television monitoring. We found one patient who probably had acquired COVID-19 through airborne-transmission. We performed airflow investigation with simulation software, whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: Of the nine individuals with COVID-19 who had been in the hematologic ward, six stayed in one multi-patient room (Room 36), and other three stayed in different rooms (Room 1, 34, 35). Guardian in room 35 was close contact to cases in room 36, and patient in room 34 used the shared bathroom for teeth brushing 40 minutes after index used. Airflow simulation revealed that air was spread from the bathroom to the adjacent room 1 while patient in room 1 did not used the shared bathroom. Airflow was associated with poor ventilation in shared bathroom due to dysfunctioning air-exhaust, grill on the door of shared bathroom and the unintended negative pressure of adjacent room. CONCLUSION: Transmission of SARS-CoV-2 in the hematologic ward occurred rapidly in the multi-patient room and shared bathroom settings. In addition, there was a case of possible airborne transmission due to unexpected airflow.
15 citations
TL;DR: In this paper, the United States Centers for Disease Control and Prevention announced the core elements for hospital ASPs, which outlines the specific structural and procedural components required to implement ASPs in 2014.
Abstract: Antimicrobial resistance has emerged as a serious global public health threat. One of the countermeasures to increased antibiotic-resistant bacterial infections is the use of an integrative intervention strategy for the selection and administration of appropriate antibiotics and for the monitoring of antibiotic use, collectively known as "Antimicrobial Stewardship Programs" (ASPs). However, since the medical environment and policies vary by country and medical facilities, ASPs also need to be applied to each facility and condition accordingly. The United States Centers for Disease Control and Prevention announced the core elements for hospital ASPs, which outlines the specific structural and procedural components required to implement ASPs in 2014. As multidrug-resistant bacterial infections and use of broad-spectrum antibiotics in Korea are on the rise, ASPs must be urgently applied to medical facilities for appropriate management of antibiotic use. However, there is an ongoing limitation to the immediate adoption and application of ASPs in Korean medical facilities due to the lack of medical workforce and related financial resources. To address this issue, efforts of medical professionals and government are required, and core elements that match the characteristics and circumstances of Korean medical facilities must be urgently developed.
13 citations
TL;DR: In this paper, the authors evaluated anakinra's safety and efficacy for treating severe coronavirus disease 2019 (COVID-19), and found a significant association was found regarding mechanical ventilation requirements in the treatment arm compared to the control group.
Abstract: This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 - 0.54, I² = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 - 0.95, I² = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 - 3.91, I² = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 - 3.03, I² = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.
TL;DR: In this article, the authors classify antiretroviral drugs into six distinct classes based on their biological function and resistance profiles: nucleoside analog reverse-transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors (NTRI), integrase strand transferase inhibitors and protease inhibitors; fusion inhibitors; and co-receptor antagonists.
Abstract: Treatment with highly active antiretroviral therapy (HAART) can prolong a patient's life-span by disrupting pivotal steps in the replication cycle of the human immunodeficiency virus-1 (HIV-1). However, drug resistance is emerging as a major problem worldwide due to the prolonged period of treatment undergone by HIV-1 patients. Since the approval of zidovudine in 1987, over thirty antiretroviral drugs have been categorized into the following six distinct classes based on their biological function and resistance profiles: (1) nucleoside analog reverse-transcriptase inhibitors; (2) non-nucleoside reverse transcriptase inhibitors; (3) integrase strand transferase inhibitors; (4) protease inhibitors; (5) fusion inhibitors; and (6) co-receptor antagonists. Additionally, several antiretroviral drugs have been developed recently, such as a long active drug, humanized antibody and pro-drug metabolized into an active form in the patient's body. Although plenty of antiretroviral drugs are beneficially used to treat patients with HIV-1, the ongoing efforts to develop antiretroviral drugs have overcome the drug resistances, adverse effects, and limited adherence of drugs observed in previous drugs to some extent. Furthermore, studies focused on agents targeting latent HIV-1 reservoirs should be strengthened, as that may lead to eradication of HIV-1.
TL;DR: In this paper, the evolution of antimicrobial resistance levels of ESKAPE microorganisms isolated during 2009 - 2010 (Period 1) and 2012 - 2014 (period 2) in a IV-level hospital in Peru was analyzed.
Abstract: BACKGOUND The members of the so-called ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are a frequent cause of severe infection, ranking among the most relevant causes of hospital infections. In Peru, few studies, often focused in a single ESKAPE microorganism, have been performed, but none providing an overall and comprehensive long-time analysis of the antibiotic resistance of ESKAPE microorganisms. In the present study, the evolution of antimicrobial resistance levels of ESKAPE microorganisms isolated during 2009 - 2010 (Period 1) and 2012 - 2014 (Period 2) in a IV-level hospital in Lima was analyzed. MATERIALS AND METHODS ESKAPE microorganisms were isolated from inpatients clinical samples. Bacterial identification, as well as antimicrobial susceptibility levels for up to 29 antimicrobial agents and presence of Extended-Spectrum β-Lactamases (only established in K. pneumoniae) were determined using automatic methods. RESULTS Of 9,918 clinical isolates, 1,917/3,777 (50.8%) [JAN/2009-JUN/2010 (Period 1)] and 4764/6141 (46.4%) [JAN/2012-DEC/2014 (Period 2)] belonged to the ESKAPE group (P <0.0001). ESKAPE were more frequent in the intensive care unit (ICU) (P <0.0001). E. faecium decreased from 5.1% to 4.1% (P <0.5), S. aureus from 10.5% to 7.0% (P <0.05), and P. aeruginosa from 12.9% to 11.6% (P <0.05), while, A. baumannii increased from 5.0% to 6.7% (P <0.05), mainly related to an increase in ICU isolates (8.4% vs. 17.1%; P <0.05). Overall, high levels of antimicrobial resistance were detected, but with few exceptions (e.g. vancomycin in E. faecium), antibiotic resistance levels remained stable or lower in Period 2. Contrarily, A. baumannii showed significantly increased resistance to different cephalosporins, carbapenems and amoxicillin plus sulbactam. CONCLUSION The introduction of a successful extensively drug-resistant A. baumannii clone in the ICU is suspected. The isolation of ESKAPE and levels of antibiotic resistance levels have reduced over time.
TL;DR: In this paper, the authors examined the risk factors for colonisation of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant CRE (CRE) patients with hematologic malignancies.
Abstract: BACKGROUND This paper aimed to inspect factors affecting febrile neutropenia patients with hematologic malignancies. The intestinal colonization rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) was assessed. The rate of subsequent ESBL-E and CRE bacteremia correlated with corresponding bacterial colonization was evaluated. Further, the risk factors for ESBL-E and CRE intestinal colonization were examined. Finally, the impact of rectal swab screening combined with adapted empirical antibiotic therapy on the mortality rate of patients with febrile neutropenia was assessed. MATERIALS AND METHODS Febrile neutropenia patients underwent rectal swabs and collection of blood culture specimens upon admission. Empirical treatment was subsequently modified according to rectal swab results if necessary. Bacteremia patients were treated according to blood culture results. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for ESBL-E and CRE fecal carriage and mortality. RESULTS In total, 201 rectal swabs and 402 blood samples were collected from 163 patients during 201 febrile neutropenia episodes. Of these episodes, 38 (18.90%) were colonized with ESBL-E and 30 (14.92%) with CRE. Bloodstream infections developed in 29/201 (14.42%) episodes. Only bacteremia episodes caused by Gram-negative bacilli were included in our analysis. The development of Gram-negative-rod bacteremia was observed in eight out of 38 (21.05%) ESBL-E colonized episodes and four out of 30 (13.33%) CRE-colonized episodes. A BSI developed in three out of 38 (7.89%) ESBL-E colonized episodes, and two out of 30 (6.66%) CRE-colonized episodes developed BSI with the respective organism. Multivariate analysis identified previous quinolone use as the only independent risk factor for fecal colonization of multi-drug-resistant (MDR) Enterobacteriaceae (ESBL-E and CRE) (odds ratio, 17.09; 95% confidence interval, 5.29 - 55.18; P <0.0001). No significant association was observed between ESBL-E and CRE carriage and increased risk of developing subsequent bacteremia. No significant differences were detected between groups receiving modified and non-modified treatments in duration of hospitalization or antibiotic therapy (univariate analysis) and 28-day mortality rate (logistic regression). CONCLUSION Quinolone exposure was a major risk factor for ESBL-E and CRE fecal carriage. Performing rectal swab screening for MDR Enterobacteriaceae and modifying empirical antibiotic therapy accordingly did not improve clinical outcomes of febrile neutropenia patients.
TL;DR: In this article, the authors conducted a web-based cross-sectional survey based on Google Forms to collect data on adverse events (AEs) after the first dose of the ChAdOx1 nCoV-19 vaccine for healthcare workers.
Abstract: Vaccination is an important strategy for controlling the coronavirus disease 2019 (COVID-19) pandemic. We conducted a web-based cross-sectional survey based on Google Forms to collect data on adverse events (AEs) after the first dose of the ChAdOx1 nCoV-19 vaccine for healthcare workers (HCWs). Among the 1,676 vaccinated HCWs, 59.5% (998/1,676) responded to the survey. In total, 809 (81.1%) respondents reported experiencing AEs. There were no serious AEs, such as anaphylaxis. The most common AE was pain at the injection site (76.2%), followed by fatigue (75.9%), myalgia (74.9%), and fever (58.4%). HCWs in the younger age group experienced significantly more AEs than in the older age group.
TL;DR: In this article, the efficacy and tolerability of ruxolitinib for adult COVID-19 patients were examined using preferred reporting items for aystematic reviews and meta-analyses (PRISMA).
Abstract: Background The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients. Materials and methods This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups. Results 168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 - 4.16; P = 0.45; I² = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I² = 0%). Conclusion Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.
TL;DR: Although pleural effusion is an uncommon finding in the COVID-19, care should be taken to avoid exposure when handling the pleural fluid sample.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected via a nasopharyngeal swab and in sputum, blood, urine, and feces. However, there is only limited data on the real-time reverse transcriptase polymerase chain reaction (RT-PCR) results of coronavirus disease 2019 (COVID-19) patients with pleural fluid. We report a case of COVID-19 with SARS-CoV-2 detected in both sputum and pleural fluid. A 68-year-old male patient came to the hospital with a chief complaint of dyspnea. He was diagnosed with lung cancer. A biopsy was performed, and a pneumothorax was found. As a result, a chest tube was placed into the right pleural space. During his hospital stay, the patient was confirmed as COVID-19 positive. We identified the presence of SARS-CoV-2 through real-time RT-PCR assay from the pleural fluid. Although pleural effusion is an uncommon finding in the COVID-19, care should be taken to avoid exposure when handling the pleural fluid sample.
TL;DR: The machine-learning techniques may play a role in differentiating between TBM and VM, and the ANN model seems to have better diagnostic performance than the non-expert clinician.
Abstract: BACKGROUND Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. MATERIAL AND METHODS For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. RESULTS The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). CONCLUSION The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.
TL;DR: In this article, the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections was evaluated.
Abstract: Background Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). Materials and methods We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I² statistic. Results The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).
TL;DR: In this article, the authors used Monte Carlo simulation to calculate the probability of target attainment, and the cumulative fraction of response (CFR) of the free area under the curve to MIC ratio (fAUIC24) was calculated.
Abstract: BACKGROUND Linezolid, an oxazolidinone antibiotic, is recommended for vancomycin-resistant enterococci (VRE). However, 100% free-drug concentration above the minimum inhibitory concentration (fT>MIC) and an area under the curve of free drug to MIC ratio (fAUC24/MIC) >100 were associated with favorable clinical outcome with less emerging resistance. A plasma trough concentration (Ctrough) of linezolid ≥9 μg/mL was also related to hematologic toxicity. Thus, linezolid dose optimization is needed for VRE treatment. The study aimed to determine the in vitro linezolid activity against clinical VRE isolates and linezolid dosing regimens in critically ill patients who met the target pharmacokinetics/pharmacodynamics (PK/PD) for VRE treatment. MATERIALS AND METHODS Enterococcal isolates from enterococcal-infected patients were obtained between 2014 and 2018 at Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment, and the cumulative fraction of response (CFR) of the free area under the curve to MIC ratio (fAUIC24) was used to calculate the fAUC24/MIC 80 - 100 and fT/MIC >85 - 100% of the interval time of administration for clinical response and microbiological eradication as well as the Ctrough ≥9 μg/mL for the probability of hematologic toxicity. RESULTS For linezolid MIC determination, the MIC median (MIC50), MIC for 90% growth (MIC90), and range for linezolid were 1.5 μg/mL, 2 μg/mL, and 0.72 - 2 μg/mL, respectively. A dosing regimen of 1,200 mg either once daily or as a divided dose every 12 h gave target attainments of fAUC24/MICs >80 and >100, which exceeded 90% for MICs ≤1 and ≤1 μg/mL, respectively, with a rate of hematologic toxicity MICs were >85% and 100%, a 1,200-mg divided dose every 12 h could cover VRE isolates having linezolid MICs ≤1 μg/mL and ≤0.75 μg/mL. Even 600 mg every 8 h and 1,200 mg as a continuous infusion gave a higher target attainment of fAUC24/MIC and a fT>MIC and the target CFR, but those regimens gave Ctrough ≥9 μg/mL rates of 40.7% and 99.6%. CONCLUSION The current dosing of 1,200 mg/day might be optimal treatment for infection by VRE isolates with documented MICs ≤1 μg/mL. For treatment of VRE with a MIC of 2 μg/mL or to achieve the target CFR, the use of linezolid with other antibiotic combinations might help achieve the PK/PD target, provide better clinical outcome, and prevent resistance.
TL;DR: In this paper, the authors provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.
Abstract: Neutralizing antibodies targeted at the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been developed and now under evaluation in clinical trials. The US Food and Drug Administration currently issued emergency use authorizations for neutralizing monoclonal antibodies in non-hospitalized patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at high risk for progressing to severe disease and/or hospitalization. In terms of this situation, there is an urgent need to investigate the clinical aspects and to develop strategies to deploy them effectively in clinical practice. Here we provide guidance for the use of anti-SARS-CoV-2 monoclonal antibodies for the treatment of COVID-19 based on the latest evidence.
TL;DR: In this paper, the effect of enteral favipiravir at a 2 × 1,600 mg loading dose and 2 × 600 mg maintenance dose for 5 days in addition to the standard COVID-19 treatment was investigated.
Abstract: BACKGROUND: The antiviral agent favipiravir is an RNA-dependent RNA polymerase (RdRp) inhibitor. MATERIALS AND METHODS: We examined patients with a clinical, laboratory, and radiological diagnosis of severe coronavirus disease 2019 (COVID-19) pneumonia. We investigated the effect of administering enteral favipiravir at a 2 × 1,600 mg loading dose and 2 × 600 mg maintenance dose for 5 days in addition to the standard COVID-19 treatment. RESULTS: In total, 180 patients, who were hospitalized at the Istanbul Tuzla State Hospital and received favipiravir treatment between March 20, 2020 and May 30, 2020, were examined. Of these, 47 patients died. Thirty-three of the patients who died were aged over 65 years (70%), indicating that fatality was higher in elderly patients. Most of those who died had at least one comorbidity. Of the 101 patients who initiated favipiravir within ≤3 days of hospitalization, 17 died (17%). Of the 79 patients who initiated favipiravir after >3 days of hospitalization, 30 died (38%) (P = 0.002). CONCLUSION: We found that initiation of favipiravir within the first 72 h after the onset of disease symptoms reduced fatality in patients with COVID-19.
TL;DR: In this paper, the authors compared the antibiotic resistance of pathogens causing CAIs, HCAIs, and hospital-acquired infections (HAIs) in Korea, and investigated the need for different empirical antibiotics therapy for CAIs and HCAI.
Abstract: BACKGROUND There have been recent proposals to categorize healthcare-associated infections (HCAIs) separately from community-acquired infections (CAIs). The aim of this study was to compare the antibiotic resistance of pathogens causing CAIs, HCAIs, and hospital-acquired infections (HAIs) in Korea, and to investigate the need for different empirical antibiotics therapy for CAIs and HCAIs. MATERIALS AND METHODS This prospective study was conducted in a university hospital between March and December 2019. Inpatients who underwent a bacterial culture within 2 days of hospitalization, with a Enterobacteriaceae strain identified at the infection site and available antibiotic susceptibility results, were included in the analysis. Infections were classified as CAIs, HCAIs or HAIs, depending on the source. RESULTS Of the 146 patients included in the analysis, the prevalence of fluoroquinolone-resistant Enterobacteriaceae was 18.8%, 38.5%, and 55.0%; the prevalence of pathogens showing third-generation cephalosporins resistance was 8.3%, 50.0%, and 60.0%; and the prevalence of pathogens showing piperacillin-tazobactam resistance was 8.3%, 7.7%, 15.0% in the CAIs, HCAIs, and HAIs groups, respectively. The prevalence of extended-spectrum beta-lactamase-positive pathogens was 6.3%, 47.3%, and 55.0% in the CAIs, HCAIs, and HAIs group, respectively, with no significant difference between the HCAIs and HAIs groups. Resistance patterns of the HCAIs group more closely resembled those of the HAIs group than those of the CAIs group. CONCLUSION The pathogens isolated from patients with HCAIs showed resistance patterns that were more similar to those of patients with HAIs than those with CAIs. Thus, CAIs and HCAIs should be distinguished from each other when selecting antibiotic agents.
TL;DR: In this article, it is recommended that paraspinal tissues, rather than spinal tissues, are collected to increase the positive rate in tissue culture, and the collected tissue sample is used in culture tests on bacteria and mycobacteria as well as pathological tests.
Abstract: Pyogenic spondylitis requires long-term antibiotics treatment and identification of the etiologic microorganism is essential. The first test in the microbiologic diagnosis of pyogenic spondylitis is a blood culture. Any microorganisms that grow in blood culture are highly likely to be the etiological microorganisms of pyogenic spondylitis. If the microbial etiology cannot be defined by the blood culture, a needle biopsy is performed on the inflamed tissues. Here, it is recommended that paraspinal tissues, rather than spinal tissues, are collected to increase the positive rate in tissue culture. If the microbial etiology cannot be defined by the first needle biopsy, another needle biopsy may be performed. The collected tissue sample is used in culture tests on bacteria and mycobacteria as well as pathological tests. If tuberculous spondylitis is suspected, polymerase chain reaction is carried out to detect Mycobacterium tuberculosis. In the case that the etiological microorganisms cannot be identified, the data of the patient regarding age, sex, vertebrae involved, history of spinal surgery or procedure, previous or concurrent urinary tract or intra-abdominal infection are analyzed. Based on this the most probable microbial etiology is determined to select the antibiotics to be used in the empiric treatment.
TL;DR: In this paper, the authors report three cases of patients with Varicella-Zoster Virus (VZV) and COVID-19 co-infections, presenting in three varied ways.
Abstract: There have been recent descriptions of the novel coronavirus disease 2019 (COVID-19) presenting as 'varicella-like exanthem'. We report three cases of patients with Varicella-Zoster Virus (VZV) and COVID-19 co-infections, presenting in three varied ways. These cases highlight the need for heightened alertness to how such co-infections can present, to pick up overlapping 'dual pathologies' during this current pandemic given that infection control measures including airborne precautions are crucial for both COVID-19 and VZV.
TL;DR: In this paper, the authors examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity.
Abstract: Background Acinetobacter baumannii has been recognized as a cause of nosocomial infection To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A baumannii (CRAB) Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity Materials and methods Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015 The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥33 μg/mL Results A total of 50 CRAB isolates were included The MIC50 and MIC90 were 64 and 128 μg/mL, respectively, for sulbactam, 256 and 2,048 μg/mL, respectively, for fosfomycin, and 1 and 4 μg/mL, respectively, for colistin In patients with creatinine clearance of 91 - 130 m/min, the dosing regimens of 180 mg every 12 h and 150 mg every 8 h achieved ≥ 90% of target of the area under the free drug plasma concentration-time curve from 0 to 24 hr (fAUC24)/MIC ≥25 against isolates MICs of ≤025 and ≤05 μg/mL, respectively, and their rates of colistin trough concentration more than ≥33 μg/mL were 35 and 54%, respectively Colistin combined with sulbactam or fosfomycin decreased the colistin MIC of CRAB isolates from 1 - 16 μg/mL to 00625 - 1 and 00625 - 2 μg/mL, respectively Based on CFR ≥ 90%, no colistin monotherapy regimens in patients with creatinine clearance of 91 - 130 mL/min were effective against all of the studied CRAB isolates For improving efficacy and reducing the risk of nephrotoxicity, colistin 150 mg given every 12 h together with sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) was effective in patients with creatinine clearance of 91 - 130 mL/min Additionally, both colistin combination regimens were effective against five colistin-resistant A baumannii isolates Conclusion Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment
TL;DR: In Korea, the prevalence of HCV is estimated to be approximately 1% Although no effective vaccine for HCV has been developed yet, highly effective and safe direct-acting antiviral therapy, which has a short treatment duration of 8 - 12 weeks, has made HCV eradication possible globally as mentioned in this paper.
Abstract: Viral hepatitis is the most important cause of acute and chronic liver disease in Korea Particularly, hepatitis B virus (HBV) is the leading cause of liver-related mortality Because of the nationwide vaccinations in the 1980s, hepatitis B surface antigen positive rates substantially decreased from 8% to 3% Moreover, the introduction of potent nucleoside or nucleotide analogs led to the effective treatment of patients who had already been infected by HBV The remaining issue has been to develop novel drugs that can cure HBV infection Hepatitis C virus (HCV), on the other hand, is a hepatotropic virus that is parenterally transmitted In Korea, the prevalence of HCV is estimated to be approximately 1% Although no effective vaccine for HCV has been developed yet, highly effective and safe direct-acting antiviral therapy, which has a short treatment duration of 8 - 12 weeks, has made HCV eradication possible globally Currently, the unsolved issue regarding HCV management is low disease awareness among patients and health care providers Therefore, nationwide testing for anti-HCV would be a solution to identify patients infected with HCV but with no symptoms Lastly, the Hepatitis A virus (HAV) is orally transmitted and results in acute hepatitis In Korea, the young adult population is a high-risk group since this group is not vaccinated against HAV More active vaccination and improved hygiene would be necessary to prevent HAV infection
TL;DR: Given the high mortality in disseminated cases, invasive fusariosis is becoming a therapeutic challenge to clinicians treating immunocompromised patients.
Abstract: Fusarium species, which are commonly found in soil, water, and organic substrates, can cause serious infections especially in immunocompromised patients. Fusarium infection is notoriously difficult to treat, because of their inherently high minimum inhibitory concentrations (MICs) to most antifungal agents. There have been limited data on invasive fusariosis in Korea. We identified 57 patients with culture-proven fusariosis at Samsung Medical Center, Seoul, Korea, from September 2003 through January 2017. Invasive fusariosis was defined as any case with at least one positive blood culture or with concurrent involvement of 2 or more non-contiguous sites. Superficial infections such as keratitis and onychomycosis were excluded. We reported 14 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, of which 6 cases were fusarium fungemia. Hematologic malignancies (7/14, 50%), solid organ transplantation (2/14, 14.2%), or immunosuppressive therapy (2/14, 14.2%), were the predominant underlying conditions. The overall mortality rate was 37%, however, that of disseminated fusariosis was up to 83%. Antifungal treatment with voriconazole or liposomal amphotericin B was commonly administered. In this report, we described the clinical characteristics and treatment outcomes of invasive fusariosis in Korea. Given the high mortality in disseminated cases, invasive fusariosis is becoming a therapeutic challenge to clinicians treating immunocompromised patients.
TL;DR: In this article, a nanoemulsion (NE) containing both chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) was used to deliver both ClPc and PM to leishmaniasis cells.
Abstract: Background Photodynamic therapy (PDT) using chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) can be effective against New World Leishmania species involved in cutaneous leishmaniasis (CL). The aim of this study is to assay the skin permeation and the antileishmanial effects of a nanoemulsion (NE) containing both ClAlPc and PM in experimental CL by Leishmania (Viannia) braziliensis. Material and methods Cremophor ELP/castor oil-based NEs were prepared by a low-energy method and characterized for their physicochemical parameters. The NEs were used to deliver both ClAlPc and PM to leishmania cells. The in vitro toxicity of NEs were tested in vitro against L. (V.) braziliensis and THP-1 cells. The in vivo toxicity was assessed in non-infected BALB/c mice. Ex-vivo permeation and retention studies using healthy mice skin were also conducted. Finally, the in vivo activity of NE-PM+ClAlPc after PDT was tested in BALB/c mice infected with parasites. Results NEs are colloidally stable with average droplet diameter of 30 nm, polydispersity index (PDI) below 0.2, and zeta potential near zero. Both promastigotes and intracellular amastigotes treated with NE-PM, NE-ClAlPc and NE-PM+ClAlPc were inhibited at >50%, >95%, >88%, respectively, after PDT with a phototoxic index (PI) >1.2. No skin ClAlPc permeation was observed. In contrast, PM skin permeation was 80-fold higher using PM-loaded NE formulation in comparison to aqueous PM solution. Topical treatment with NE formulations showed no signs of local toxicity or genotoxicity. In addition, concentrations of PM between 27.3 - 292.5 μM/25 mg of tissue were detected in different organs. In vivo, the NE-PM+ClAlPc treatment did not reduce skin lesions. Conclusion The Cremophor ELP/castor oil NE formulation increases the permeation of PM through the skin and can be used to co-deliver PM plus ClAlPc for combined PDT protocols. However, the lack of efficacy in the in vivo model evidences that the therapeutical scheme has to be improved.