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47 ud af 47 tidsskrifter valgt, søgeord (pneumoni) valgt, emner højest 180 dage gamle, sorteret efter nyeste først.
318 emner vises.
Sha WeiTingting XuYuxin ChenKai Zhoua Shenzhen Institute of Respiratory Diseases, Second Clinical Medical College (Shenzhen People's Hospital), Jinan University; the First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen, People’s Republic of Chinab Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China
Emerg Microbes Infect, 30.12.2023
Tilføjet 30.12.2023
Zixin Cai, Bilian Liu
PLoS One Infectious Diseases, 29.12.2023
Tilføjet 29.12.2023
by Zixin Cai, Bilian Liu Objective In December 2019, a novel pneumonia associated with the 2019 coronavirus emerged unexpectedly. However, limited data exist on the effects of COVID-19 on ACTH and cortisol levels. To address this gap in knowledge, we conducted a meta-analysis of published studies on the relationship between COVID-19 patients and their ACTH and cortisol levels. Methods We conducted a thorough search of the PubMed, Embase, Cochrane Library, and Web of Science databases up until May 2023. We assessed the relevance of each study we found, specifically looking for studies that reported on ACTH and cortisol levels in COVID-19 patients. We calculated weighted mean differences (WMD) and 95% confidence intervals (CI) to investigate the relationship between ACTH and cortisol levels in COVID-19 patients. We evaluated the quality of each study using the Newcastle Ottawa scale (NOS), and we assessed publication bias using Begg’s rank correlation test, Egger’s test, and funnel plot. We conducted our meta-analysis using the Stata 12.0 (Stata Corporation, TX). Results Our search yielded nine studies that met our inclusion criteria, which included a total of 440 COVID-19 patients and 474 controls, with data up to May 2023. Seven of these studies reported on ACTH levels, and six studies reported on cortisol levels. Our findings revealed that COVID-19 patients had significantly higher levels of cortisol compared to controls (WMD 3.46 (95% CI 2.29 to 4.62)). However, there was no significant difference in ACTH levels between COVID-19 patients and controls (WMD 1.58 (95% CI -5.79 to 8.94)). Conclusions This meta-analysis indicates a potential relationship between elevated cortisol levels and COVID-19 infection. However, more well-designed, adequately powered, randomized controlled trial will be needed to assess the use of cortisol in patients with COVID-19 infection.
Læs mere Tjek på PubMedFatema Binte Alam, Prajoy Podder, M. Rubaiyat Hossain Mondal
PLoS One Infectious Diseases, 29.12.2023
Tilføjet 29.12.2023
by Fatema Binte Alam, Prajoy Podder, M. Rubaiyat Hossain Mondal Early evaluation and diagnosis can significantly reduce the life-threatening nature of lung diseases. Computer-aided diagnostic systems (CADs) can help radiologists make more precise diagnoses and reduce misinterpretations in lung disease diagnosis. Existing literature indicates that more research is needed to correctly classify lung diseases in the presence of multiple classes for different radiographic imaging datasets. As a result, this paper proposes RVCNet, a hybrid deep neural network framework for predicting lung diseases from an X-ray dataset of multiple classes. This framework is developed based on the ideas of three deep learning techniques: ResNet101V2, VGG19, and a basic CNN model. In the feature extraction phase of this new hybrid architecture, hyperparameter fine-tuning is used. Additional layers, such as batch normalization, dropout, and a few dense layers, are applied in the classification phase. The proposed method is applied to a dataset of COVID-19, non-COVID lung infections, viral pneumonia, and normal patients’ X-ray images. The experiments take into account 2262 training and 252 testing images. Results show that with the Nadam optimizer, the proposed algorithm has an overall classification accuracy, AUC, precision, recall, and F1-score of 91.27%, 92.31%, 90.48%, 98.30%, and 94.23%, respectively. Finally, these results are compared with some recent deep-learning models. For this four-class dataset, the proposed RVCNet has a classification accuracy of 91.27%, which is better than ResNet101V2, VGG19, VGG19 over CNN, and other stand-alone models. Finally, the application of the GRAD-CAM approach clearly interprets the classification of images by the RVCNet framework.
Læs mere Tjek på PubMedInfection, 28.12.2023
Tilføjet 28.12.2023
Abstract Purpose Although diagnostic stewardship issues in clinical microbiology harbor an optimization potential for anti-infective consumption, they are only marginally addressed in antimicrobial stewardship (AMS) programs. As part of an AMS point prevalence (PPS) survey we therefore aimed to gain a more dynamic view on the microbiological awareness within therapeutic regimens. By examining whether initial microbiological sampling was performed and in which way microbiological results were incorporated into further treatment considerations we sought to find out to what extent these points determine the appropriateness of treatment regimens. Methods PPS was performed at the University Hospital Salzburg (1524 beds) in May 2021. Relevant data was determined from the patient charts and the appropriateness of anti-infective use was assessed using predefined quality indicators. Six months after the PPS, a questionnaire was administered to clinicians to obtain information on the use of microbiological findings and their relevance in the clinic. Results Lack of microbiological awareness in the clinical setting proved to be the key reason for an overall inadequate use of anti-infectives (35.4% of cases rated as inadequate), ahead of the aspects of dose (24.1%), empirical therapy (20.3%) and treatment duration (20.2%). This was particularly the case for broad-acting agents and was most evident in urinary tract infections, skin and soft tissue infections, and pneumonia. The results of the questionnaire indicate a discrepancy between the physicians surveyed and the routine clinical setting. Conclusion A high potential in improving the use of anti-infectives in hospitals seems to lie in a strong emphasis on microbiological diagnostic stewardship measures.
Læs mere Tjek på PubMedInfection, 28.12.2023
Tilføjet 28.12.2023
Abstract Background Interstitial lung disease (ILD) is a new risk category for pneumocystis pneumonia (PCP) with a high mortality rate. The definite diagnostic criteria of PCP in ILD patients have not been established until now. The aims of this study were to identify potential risk factors of PCP in patients with ILD, and to evaluate the performance of metagenomic next-generation sequencing (mNGS), CD4 + T cell count, (1–3)-β-d-Glucan (BG) and lactate dehydrogenase (LDH) in the diagnosis of PCP in ILD patients. Methods This is a retrospective, single-center, case–control study. ILD patients who underwent mNGS from December 2018 to December 2022 were included in the study. Based on the diagnosis criteria of PCP, these patients were divided into PCP-ILD and non-PCP-ILD groups. The potential risk factors for PCP occurrence in ILD patients were analysed via logistic regression. The diagnostic efficacy of mNGS was compared with serological biomarkers. Results 92 patients with ILD were enrolled, 31 of which had a definite PCP and were assigned to the PCP-ILD group while 61 were to the non-PCP-ILD group. The infection rate of PJ in ILD patients was 33.7% (31/92). The history of glucocorticoid therapy, CD4 + T cell count, BG level and traction bronchiectasis on HRCT were associated with PCP occurrence in ILD patients. LDH level did not reach statistical significance in the logistic regression analysis. mNGS was confirmed as the most accurate test for PCP diagnosis in ILD patients. Conclusion ILD is a new risk group of PCP with high PCP prevalence. Clinicians should pay close attention to the occurrence of PCP in ILD patients who possess the risk factors of previous glucocorticoid therapy, decreased CD4 + T cell count, increased BG level and absence of traction bronchiectasis on HRCT. mNGS showed the most excellent performance for PCP diagnosis in ILD patients. Peripheral blood CD4 + T cell count and BG level are alternative diagnostic methods for PCP in ILD patients. However, the diagnostic value of serum LDH level was limited in ILD patients.
Læs mere Tjek på PubMedBMC Infectious Diseases, 28.12.2023
Tilføjet 28.12.2023
Abstract Background Klebsiella pneumoniae is a pathogen that often infects patients in clinical practice. Due to its high virulent and drug resistance, infected patients are difficult to treat. In clinical practice, Klebsiella pneumoniae can infect patients\' intestines, intestines, blood, etc., causing pathological changes. However, there is relatively little information on the impact of Klebsiella pneumoniae on intestinal inflammation and microbial populations. Zebrafish is an excellent biomedical model that has been successfully applied to the virulence assessment of Klebsiella pneumoniae. Methods In this study, three clinically isolated representative strains of Klebsiella pneumoniae (high virulence non-resistant, high virulence resistant, and low virulence resistant) were used to infect zebrafish, and their effects on intestinal colonization, inflammation, pathology, and microbial diversity were tested. Results Enzyme-linked immunoassay (ELISA) showed that Klebsiella pneumoniae significantly increased levels of the cytokines interleukin-1α (Il-1α), interleukin-1β (Il-1β), and tumor necrosis factor-α (Tnf-α), which increased inflammatory symptoms. Hematoxylin eosin staining(H&S) showed that Klebsiella pneumoniae treatment caused intestinal lesions in zebrafish, in which KP1053 exposure significantly decreased the number of goblet cells, KP1195 caused epithelial dissolution and exfoliation. In addition, Klebsiella pneumoniae disturbed the composition of intestinal microbiota, and the Shannon index increased, which increased the number of harmful bacteria. Conclusions Klebsiella pneumoniae infection can lead to intestinal colonization, inflammation, pathological changes, and changes in microbial biodiversity. This study provides a reference for the intestinal pathology of clinical Klebsiella pneumoniae infection.
Læs mere Tjek på PubMedInfection, 27.12.2023
Tilføjet 27.12.2023
Abstract Purpose Although diagnostic stewardship issues in clinical microbiology harbor an optimization potential for anti-infective consumption, they are only marginally addressed in antimicrobial stewardship (AMS) programs. As part of an AMS point prevalence (PPS) survey we therefore aimed to gain a more dynamic view on the microbiological awareness within therapeutic regimens. By examining whether initial microbiological sampling was performed and in which way microbiological results were incorporated into further treatment considerations we sought to find out to what extent these points determine the appropriateness of treatment regimens. Methods PPS was performed at the University Hospital Salzburg (1524 beds) in May 2021. Relevant data was determined from the patient charts and the appropriateness of anti-infective use was assessed using predefined quality indicators. Six months after the PPS, a questionnaire was administered to clinicians to obtain information on the use of microbiological findings and their relevance in the clinic. Results Lack of microbiological awareness in the clinical setting proved to be the key reason for an overall inadequate use of anti-infectives (35.4% of cases rated as inadequate), ahead of the aspects of dose (24.1%), empirical therapy (20.3%) and treatment duration (20.2%). This was particularly the case for broad-acting agents and was most evident in urinary tract infections, skin and soft tissue infections, and pneumonia. The results of the questionnaire indicate a discrepancy between the physicians surveyed and the routine clinical setting. Conclusion A high potential in improving the use of anti-infectives in hospitals seems to lie in a strong emphasis on microbiological diagnostic stewardship measures.
Læs mere Tjek på PubMedInfection, 27.12.2023
Tilføjet 27.12.2023
Abstract Background Interstitial lung disease (ILD) is a new risk category for pneumocystis pneumonia (PCP) with a high mortality rate. The definite diagnostic criteria of PCP in ILD patients have not been established until now. The aims of this study were to identify potential risk factors of PCP in patients with ILD, and to evaluate the performance of metagenomic next-generation sequencing (mNGS), CD4 + T cell count, (1–3)-β-d-Glucan (BG) and lactate dehydrogenase (LDH) in the diagnosis of PCP in ILD patients. Methods This is a retrospective, single-center, case–control study. ILD patients who underwent mNGS from December 2018 to December 2022 were included in the study. Based on the diagnosis criteria of PCP, these patients were divided into PCP-ILD and non-PCP-ILD groups. The potential risk factors for PCP occurrence in ILD patients were analysed via logistic regression. The diagnostic efficacy of mNGS was compared with serological biomarkers. Results 92 patients with ILD were enrolled, 31 of which had a definite PCP and were assigned to the PCP-ILD group while 61 were to the non-PCP-ILD group. The infection rate of PJ in ILD patients was 33.7% (31/92). The history of glucocorticoid therapy, CD4 + T cell count, BG level and traction bronchiectasis on HRCT were associated with PCP occurrence in ILD patients. LDH level did not reach statistical significance in the logistic regression analysis. mNGS was confirmed as the most accurate test for PCP diagnosis in ILD patients. Conclusion ILD is a new risk group of PCP with high PCP prevalence. Clinicians should pay close attention to the occurrence of PCP in ILD patients who possess the risk factors of previous glucocorticoid therapy, decreased CD4 + T cell count, increased BG level and absence of traction bronchiectasis on HRCT. mNGS showed the most excellent performance for PCP diagnosis in ILD patients. Peripheral blood CD4 + T cell count and BG level are alternative diagnostic methods for PCP in ILD patients. However, the diagnostic value of serum LDH level was limited in ILD patients.
Læs mere Tjek på PubMedSafura-Luise Heidari, Malene Hove-Skovsgaard, Nicoline Stender Arentoft, Anne-Sophie W. Svartstein, Dina Leth Møller, Christian Salgård Jensen, Thomas Benfield, Jens-Ulrik Stæhr Jensen, Rebekka Faber Thudium, Susanne D. Nielsen
International Journal of Infectious Diseases, 27.12.2023
Tilføjet 27.12.2023
Respiratory infections, including pneumonia, are common causes of hospital admission in people with HIV (PWH) [1]. A multicenter study including 10,851 PWH found that pneumonia was the most frequently observed severe bacterial non-AIDS-defining infection in PWH [2]. Prior to the introduction of combination antiretroviral therapy (cART), incidence rates of pneumonia up to 90 cases per 1000 person-years were reported in USA, Europe, and Africa, corresponding to a 25-fold higher risk of bacterial pneumonia in PWH compared to the general population [3], [4].
Læs mere Tjek på PubMedInfection, 24.12.2023
Tilføjet 24.12.2023
Abstract Purpose The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. Methods Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. Results The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-β, SDF-1α, TNF-α, TNF-β, VEGF, PDGF-BB, TRAIL, β-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. Conclusion Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.
Læs mere Tjek på PubMedInfection, 23.12.2023
Tilføjet 23.12.2023
Abstract Purpose The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. Methods Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. Results The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-β, SDF-1α, TNF-α, TNF-β, VEGF, PDGF-BB, TRAIL, β-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. Conclusion Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.
Læs mere Tjek på PubMedInfection, 23.12.2023
Tilføjet 23.12.2023
Abstract Background Nosocomial bloodstream infections (nBSI) have emerged as a clinical concern for physicians treating COVID-19 patients. In this study, we aimed to evaluate the effectiveness of a multiplex ddPCR in detecting bacterial pathogens in the blood of COVID-19 critically ill patients. Methods This prospective diagnostic study included RT-PCR-confirmed COVID-19 patients admitted to our hospital from December 2022 to February 2023. A multiplex ddPCR assay was used to detect common bacterial pathogens and AMR genes in blood samples of the patients, along with antimicrobial susceptibility testing (AST). The diagnostic performance of the ddPCR assay was evaluated by comparing the results with those obtained through blood culture and clinical diagnosis. Additionally, the ability of ddPCR in detecting bacterial resistance was compared with the AST results. Results Of the 200 blood samples collected from 184 patients, 45 (22.5%) were positive using blood culture, while 113 (56.5%) were positive for bacterial targets using the ddPCR assay. The ddPCR assay outperformed blood culture in pathogen detection rate, mixed infection detection rate, and fungal detection rate. Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens in COVID-19 critically ill patients, followed by Enterococcus and Streptococcus. Compared to blood culture, ddPCR achieved a sensitivity of 75.5%, specificity of 51.0%, PPV of 30.9%, and NPV of 87.8%, respectively. However, there were significant differences in sensitivity among different bacterial species, where Gram-negative bacteria have the highest sensitivity of 90.3%. When evaluated on the ground of clinical diagnosis, the sensitivity, specificity, PPV and NPV of ddPCR were 78.1%, 90.5%, 94.7%, and 65.5%, respectively. In addition, the ddPCR assay detected 23 cases of blaKPC, which shown a better consistent with clinical test results than other detected AMR genes. Compared to blaKPC, there were few other AMR genes detected, indicating that the application of other AMR gene detection in the COVID-19 critically ill patients was limited. Conclusion The multiplex ddPCR assay had a significantly higher pathogen detection positivity than the blood culture, which could be an effective diagnostic tool for BSIs in COVID-19 patients and to improve patient outcomes and reduce the burden of sepsis on the healthcare system, though there is room for optimization of the panels used.- Adjusting the targets to include E. faecalis and E. faecium as well as Candida albicans and Candida glabrata could improve the ddPCR\' s effectiveness. However, further research is needed to explore the potential of ddPCR in predicting bacterial resistance through AMR gene detection.
Læs mere Tjek på PubMedInfection, 23.12.2023
Tilføjet 23.12.2023
Abstract Background Existing panels for lower respiratory tract infections (LRTIs) are slow and lack quantification of important pathogens and antimicrobial resistance, which are not solely responsible for their complex etiology and antibiotic resistance. BioFire FilmArray Pneumonia (PN) panels may provide rapid information on their etiology. Methods The bronchoalveolar lavage fluid of 187 patients with LRTIs was simultaneously analyzed using a PN panel and cultivation, and the impact of the PN panel on clinical practice was assessed. The primary endpoint was to compare the consistency between the PN panel and conventional microbiology in terms of etiology and drug resistance, as well as to explore the clinical significance of the PN panel. The secondary endpoint was pathogen detection using the PN panel in patients with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). Results Fifty-seven patients with HAP and 130 with CAP were included. The most common pathogens of HAP were Acinetobacter baumannii and Klebsiella pneumoniae, with the most prevalent antimicrobial resistance (AMR) genes being CTX-M and KPC. For CAP, the most common pathogens were Haemophilus influenzae and Staphylococcus aureus, with the most frequent AMR genes being CTX-M and VIM. Compared with routine bacterial culture, the PN panel demonstrated an 85% combined positive percent agreement (PPA) and 92% negative percent agreement (NPA) for the qualitative identification of 13 bacterial targets. PN detection of bacteria with higher levels of semi-quantitative bacteria was associated with more positive bacterial cultures. Positive concordance between phenotypic resistance and the presence of corresponding AMR determinants was 85%, with 90% positive agreement between CTX-M-type extended-spectrum beta-lactamase gene type and phenotype and 100% agreement for mecA/C and MREJ. The clinical benefit of the PN panel increased by 25.97% compared with traditional cultural tests. Conclusion The bacterial pathogens and AMR identified by the PN panel were in good agreement with conventional cultivation, and the clinical benefit of the PN panel increased by 25.97% compared with traditional detection. Therefore, the PN panel is recommended for patients with CAP or HAP who require prompt pathogen diagnosis and resistance identification.
Læs mere Tjek på PubMedBMC Infectious Diseases, 21.12.2023
Tilføjet 21.12.2023
Abstract Background Klebsiella pneumoniae is a pathogen that often infects patients in clinical practice. Due to its high virulent and drug resistance, infected patients are difficult to treat. In clinical practice, Klebsiella pneumoniae can infect patients\' intestines, intestines, blood, etc., causing pathological changes. However, there is relatively little information on the impact of Klebsiella pneumoniae on intestinal inflammation and microbial populations. Zebrafish is an excellent biomedical model that has been successfully applied to the virulence assessment of Klebsiella pneumoniae. Methods In this study, three clinically isolated representative strains of Klebsiella pneumoniae (high virulence non-resistant, high virulence resistant, and low virulence resistant) were used to infect zebrafish, and their effects on intestinal colonization, inflammation, pathology, and microbial diversity were tested. Results Enzyme-linked immunoassay (ELISA) showed that Klebsiella pneumoniae significantly increased levels of the cytokines interleukin-1α (Il-1α), interleukin-1β (Il-1β), and tumor necrosis factor-α (Tnf-α), which increased inflammatory symptoms. Hematoxylin eosin staining(H&S) showed that Klebsiella pneumoniae treatment caused intestinal lesions in zebrafish, in which KP1053 exposure significantly decreased the number of goblet cells, KP1195 caused epithelial dissolution and exfoliation. In addition, Klebsiella pneumoniae disturbed the composition of intestinal microbiota, and the Shannon index increased, which increased the number of harmful bacteria. Conclusions Klebsiella pneumoniae infection can lead to intestinal colonization, inflammation, pathological changes, and changes in microbial biodiversity. This study provides a reference for the intestinal pathology of clinical Klebsiella pneumoniae infection.
Læs mere Tjek på PubMedInfection, 21.12.2023
Tilføjet 21.12.2023
Abstract Background Nosocomial bloodstream infections (nBSI) have emerged as a clinical concern for physicians treating COVID-19 patients. In this study, we aimed to evaluate the effectiveness of a multiplex ddPCR in detecting bacterial pathogens in the blood of COVID-19 critically ill patients. Methods This prospective diagnostic study included RT-PCR-confirmed COVID-19 patients admitted to our hospital from December 2022 to February 2023. A multiplex ddPCR assay was used to detect common bacterial pathogens and AMR genes in blood samples of the patients, along with antimicrobial susceptibility testing (AST). The diagnostic performance of the ddPCR assay was evaluated by comparing the results with those obtained through blood culture and clinical diagnosis. Additionally, the ability of ddPCR in detecting bacterial resistance was compared with the AST results. Results Of the 200 blood samples collected from 184 patients, 45 (22.5%) were positive using blood culture, while 113 (56.5%) were positive for bacterial targets using the ddPCR assay. The ddPCR assay outperformed blood culture in pathogen detection rate, mixed infection detection rate, and fungal detection rate. Acinetobacter baumannii and Klebsiella pneumoniae were the most commonly detected pathogens in COVID-19 critically ill patients, followed by Enterococcus and Streptococcus. Compared to blood culture, ddPCR achieved a sensitivity of 75.5%, specificity of 51.0%, PPV of 30.9%, and NPV of 87.8%, respectively. However, there were significant differences in sensitivity among different bacterial species, where Gram-negative bacteria have the highest sensitivity of 90.3%. When evaluated on the ground of clinical diagnosis, the sensitivity, specificity, PPV and NPV of ddPCR were 78.1%, 90.5%, 94.7%, and 65.5%, respectively. In addition, the ddPCR assay detected 23 cases of blaKPC, which shown a better consistent with clinical test results than other detected AMR genes. Compared to blaKPC, there were few other AMR genes detected, indicating that the application of other AMR gene detection in the COVID-19 critically ill patients was limited. Conclusion The multiplex ddPCR assay had a significantly higher pathogen detection positivity than the blood culture, which could be an effective diagnostic tool for BSIs in COVID-19 patients and to improve patient outcomes and reduce the burden of sepsis on the healthcare system, though there is room for optimization of the panels used.- Adjusting the targets to include E. faecalis and E. faecium as well as Candida albicans and Candida glabrata could improve the ddPCR\' s effectiveness. However, further research is needed to explore the potential of ddPCR in predicting bacterial resistance through AMR gene detection.
Læs mere Tjek på PubMedInfection, 21.12.2023
Tilføjet 21.12.2023
Abstract Background Existing panels for lower respiratory tract infections (LRTIs) are slow and lack quantification of important pathogens and antimicrobial resistance, which are not solely responsible for their complex etiology and antibiotic resistance. BioFire FilmArray Pneumonia (PN) panels may provide rapid information on their etiology. Methods The bronchoalveolar lavage fluid of 187 patients with LRTIs was simultaneously analyzed using a PN panel and cultivation, and the impact of the PN panel on clinical practice was assessed. The primary endpoint was to compare the consistency between the PN panel and conventional microbiology in terms of etiology and drug resistance, as well as to explore the clinical significance of the PN panel. The secondary endpoint was pathogen detection using the PN panel in patients with community-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). Results Fifty-seven patients with HAP and 130 with CAP were included. The most common pathogens of HAP were Acinetobacter baumannii and Klebsiella pneumoniae, with the most prevalent antimicrobial resistance (AMR) genes being CTX-M and KPC. For CAP, the most common pathogens were Haemophilus influenzae and Staphylococcus aureus, with the most frequent AMR genes being CTX-M and VIM. Compared with routine bacterial culture, the PN panel demonstrated an 85% combined positive percent agreement (PPA) and 92% negative percent agreement (NPA) for the qualitative identification of 13 bacterial targets. PN detection of bacteria with higher levels of semi-quantitative bacteria was associated with more positive bacterial cultures. Positive concordance between phenotypic resistance and the presence of corresponding AMR determinants was 85%, with 90% positive agreement between CTX-M-type extended-spectrum beta-lactamase gene type and phenotype and 100% agreement for mecA/C and MREJ. The clinical benefit of the PN panel increased by 25.97% compared with traditional cultural tests. Conclusion The bacterial pathogens and AMR identified by the PN panel were in good agreement with conventional cultivation, and the clinical benefit of the PN panel increased by 25.97% compared with traditional detection. Therefore, the PN panel is recommended for patients with CAP or HAP who require prompt pathogen diagnosis and resistance identification.
Læs mere Tjek på PubMedAnayochukwu E. Anyasodor, Kedir Y. Ahmed, Uchechukwu L. Osuagwu, Nnamdi C. Mgbemena, Bernd H. Kalinna, Subash Thapa, Shakeel Mahmood, Allen G. Ross
PLoS One Infectious Diseases, 21.12.2023
Tilføjet 21.12.2023
by Anayochukwu E. Anyasodor, Kedir Y. Ahmed, Uchechukwu L. Osuagwu, Nnamdi C. Mgbemena, Bernd H. Kalinna, Subash Thapa, Shakeel Mahmood, Allen G. Ross Background In countries with high child mortality rates, such as Nigeria, early intervention for common childhood illnesses (e.g., pneumonia and malaria) is essential for improving clinical outcomes. The timely reporting and treatment of fever is therefore critical in making a differential diagnosis and choosing an appropriate course of treatment. The present study aimed to investigate the prevalence and major risk factors associated with delays in seeking treatment for fever in children under five years of age in Nigeria. Methods This study used a total weighted sample of 7,466 children under five years of age from the 2018 National Nigerian Demographic and Health Survey. Multivariable binary logistic regression modelling was used to investigate the association between predisposing, enabling, need, health service and community level factors, and delay in treatment-seeking for fever. Results We report the delays in seeking treatment for childhood fever that was reported by mothers in the last two weeks prior to the national survey. The prevalence for delayed treatment was 62.1% (95% confidence interval [CI]: 60.1%, 64.1%). Our findings showed that there were fewer delays in seeking treatment in children aged 24–59 months (adjusted odds ratio [aOR] = 0.79, 95% CI: 0.68, 0.93), among mothers who were formally employed (aOR = 0.84; 95% CI: 0.73, 0.96), regularly attended antenatal services (aOR = 0.76, 95%CI: 0.66, 0.88), and for those who resided in wealthier households (aOR = 0.71; 95% CI: 0.56, 0.89). Children whose mothers resided in the North-West geopolitical zone of Nigeria were less likely to delay seeking treatment for fever (aOR = 0.55; 95% CI: 0.42, 0.73). However, mothers who had an unwanted pregnancy had a higher odds of delaying treatment for childhood fever (aOR = 1.58; 95% CI: 1.05, 2.39). Conclusion There were significant delays in seeking treatment for childhood fever in poorer homes found in geopolitically unstable zones of Nigeria. Mothers who were poor, unemployed, and with younger children (
Læs mere Tjek på PubMedLE Hermans, CM Centner, CM Morel, O Mbamalu, C Bonaconsa, C Ferreyra, O Lindahl, M Mendelson
International Journal of Infectious Diseases, 21.12.2023
Tilføjet 21.12.2023
Communicable diseases are the foremost cause of morbidity and mortality in sub-Saharan Africa (SSA).[1] This trend is mainly driven by the pandemics of HIV, tuberculosis, malaria, and COVID-19, neglected tropical diseases, and pneumonia and diarrhoeal disease in children.[2–4] The rising incidence of antimicrobial resistant (AMR) bacterial infections threatens to compound this already significant burden. A recent survey estimated that in 2019, the four global regions most heavily affected by AMR were all in SSA.[5]
Læs mere Tjek på PubMedHenley, J., Brookes-Howell, L., Euden, J., Pallmann, P., Llewelyn, M., Howard, P., Powell, N., Dark, P., Szakmany, T., Hellyer, T. P., Albur, M., Hamilton, R., Prestwich, G., Ogden, M., Maboshe, W., Sandoe, J., Thomas-Jones, E., Carrol, E., on behalf of the PEACH study group (Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients), on behalf of the PEACH consortium (Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients), Albur, Bond, Gerver, Hopkins, McCullagh, Parsons, Partridge, Shaw, Shinkins, Todd, West
BMJ Open, 20.12.2023
Tilføjet 20.12.2023
ObjectiveTo explore and model factors affecting antibiotic prescribing decision-making early in the pandemic. DesignSemistructured qualitative interview study. SettingNational Health Service (NHS) trusts/health boards in England and Wales. ParticipantsClinicians from NHS trusts/health boards in England and Wales. MethodIndividual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions. ResultsDuring the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed. ConclusionThis study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic. Trial registration number ISRCTN66682918.
Læs mere Tjek på PubMedBMC Infectious Diseases, 20.12.2023
Tilføjet 20.12.2023
Abstract Background Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. Methods We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. Result During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p
Læs mere Tjek på PubMedBMC Infectious Diseases, 19.12.2023
Tilføjet 19.12.2023
Abstract Background Data regarding the clinical effects of bacteremia on severe community-acquired pneumonia (CAP) are limited. Thus, we investigated clinical characteristics and outcomes of severe CAP patients with bacteremia compared with those of subjects without bacteremia. In addition, we evaluated clinical factors associated with bacteremia at the time of sepsis awareness. Methods We enrolled sepsis patients diagnosed with CAP at emergency departments (EDs) from an ongoing nationwide multicenter observational registry, the Korean Sepsis Alliance, between September 2019 and December 2020. For evaluation of clinical factors associated with bacteremia, we divided eligible patients into bacteremia and non-bacteremia groups, and logistic regression analysis was performed using the clinical characteristics at the time of sepsis awareness. Result During the study period, 1,510 (47.9%) sepsis patients were caused by CAP, and bacteremia was identified in 212 (14.0%) patients. Septic shock occurred more frequently in the bacteremia group than in the non-bacteremia group (27.4% vs. 14.8%; p
Læs mere Tjek på PubMedToshiyuki Sumi, Kotomi Terai, Keito Suzuki, Yuta Koshino, Takumi Ikeda, Hiroki Watanabe, Yuichi Yamada, Hirofumi Chiba
American Journal of Respiratory and Critical Care Medicine , 15.12.2023
Tilføjet 15.12.2023
American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 12, Page e47-e48, December 15, 2023.
Læs mere Tjek på PubMedJournal of Infectious Diseases, 15.12.2023
Tilføjet 15.12.2023
Abstract Background Host-response biomarkers to differentiate bacterial from viral etiology in children with respiratory infections have shown high accuracies, but are understudied in Mycoplasma pneumoniae (Mp) infections.Methods We compared BV scores (0-34 indicating viral, and 66-100 indicating bacterial etiology), TRAIL (pg/mL), IP-10 (pg/mL), and CRP (mg/L) serum levels between Mp positive (Mp+) and negative (Mp-) community-acquired pneumonia (CAP). We performed receiver operating characteristic (ROC) curve analyses for clinical features and biomarkers.Results Of 80 CAP patients (median age 6.3 years, 57.5% male), 26 were Mp + CAP. By comparing Mp + CAP with Mp–CAP patients, BV scores were lower (median 14.0, IQR 3.0–27.8 vs. 54.0, IQR 12.0–84.8; P = 0.0008), TRAIL levels were higher (86.5, IQR 67.4–123.0 vs. 65.5, IQR 42.5–103.9; P = 0.025), CRP levels were lower (12.9, IQR 4.0–22.3 vs. 36.7, IQR 13.0–132.8; P = 0.0019), and IP-10 levels were comparable (366.0, IQR 150.2–603.8 vs. 331.0, IQR 154.3–878.8; P = 0.73). ROC analyses yielded a comparable discriminatory accuracy for the combination of age, fever duration, respiratory symptoms duration, with either procalcitonin or BV (AUC 0.87 vs. 0.86, P = 0.94).Conclusions Children with Mp + CAP have atypically low, viral levels of the BV score, underscoring the complementary role of microbiological testing.
Læs mere Tjek på PubMedJuan de Dios Jordán Chaves, Rubén Lobato Cano, Javier Casas Ciria, Carolina Freyre Carrillo, Jose Diego Santotoribio Camacho, María Francisca de la Rubia Martín
Clinical Microbiology and Infection, 15.12.2023
Tilføjet 15.12.2023
Pseudomonas aeruginosa (PAE) is an important cause of both community and nosocomial human infections. The PAE is one of the most common pathogens isolated from respiratory tract specimens in patients with bronchiectasis and causes high mortality in patients with ventilator-associated pneumonia (1).
Læs mere Tjek på PubMedJoe Wee Jian Ong, Kai Sen Tan, Joseph Jing Xian Lee, Ju Ee Seet, Hyung Won Choi, Siok Ghee Ler, Jayantha Gunaratne, Teluguakula Narasaraju, Lok‐To Sham, Volker Patzel, Vincent T. Chow
Journal of Medical Virology, 13.12.2023
Tilføjet 13.12.2023
Nascimento, G. M., Gomes Rodrigues, D. L., Mangas Catarino, D. G., Piastrelli, F. T., Cheno, M. Y., Braz, K. C. C., Oliveira Alves, L. B., Avezum, A., Veiga, V. C., Zavascki, A. P., Tomazini, B., Besen, B., Pereira, A. J., Marques de Pinho, A. P. N., De Oliveira Junior, H. A.
BMJ Open, 9.12.2023
Tilføjet 9.12.2023
IntroductionCertain criteria for ventilator-associated events (VAE) definition might influence the type of an event, its detection rate and consequently the resource expenditure in intensive care unit. The Impact of Infections by Antimicrobial-Resistant Microorganisms - Ventilator-Associated Pneumonia (IMPACTO MR-PAV) aims to evaluate the incidence and diagnostic accuracy of ventilator-associated pneumonia (VAP) using the current criteria for VAP surveillance in Brazil versus the VAE criteria defined by the US National Healthcare Safety Network-Center for Diseases Control and Prevention (CDC) criteria. Methods and analysisThe study will be conducted in around 15 centres across Brazil from October 2022 to December 2023. Trained healthcare professionals will collect data and compare the incidence of VAP using both the current criteria for VAP surveillance in Brazil and the VAE criteria defined by the CDC. The accuracy of the two criteria for identifying VAP will also be analysed. It will also characterise other events associated with mechanical ventilation (ventilator-associated condition, infection-related ventilator-associated complication) and adjudicate VAP reported to the Brazilian Health Regulatory Agency (ANVISA) using current epidemiological diagnostic criteria. Ethics and disseminationThis study was approved by the Institutional Review Board under the number 52354721.0.1001.0070. The study’s primary outcome measure will be the incidence of VAP using the two different surveillance criteria, and the secondary outcome measures will be the accuracy of the two criteria for identifying VAP and the adjudication of VAP reported to ANVISA. The results will contribute to the improvement of VAP surveillance in Brazil and may have implications for other countries that use similar criteria. Trial registration numberNCT05589727; Clinicaltrials.gov.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.12.2023
Tilføjet 8.12.2023
Abstract Purpose To examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course. Materials and methods The clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.12.2023
Tilføjet 8.12.2023
Abstract Background Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND). Case presentation A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum. Conclusions The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment.
Læs mere Tjek på PubMedBMC Infectious Diseases, 8.12.2023
Tilføjet 8.12.2023
Abstract Purpose To examine the clinical characteristics of adult patients with community-acquired spontaneous bacterial meningitis (CASBM) with a fulminant clinical course. Materials and methods The clinical features and therapeutic outcomes of 127 adult CASBM patients were analyzed. The patients were divided into two groups as those with and without a fulminant clinical course. Fulminant clinical course was defined as meningitis presenting initially with marked consciousness disturbance (Glasgow Coma Scale score
Læs mere Tjek på PubMedBMC Infectious Diseases, 7.12.2023
Tilføjet 7.12.2023
Abstract Background Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND). Case presentation A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum. Conclusions The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment.
Læs mere Tjek på PubMedBMC Infectious Diseases, 7.12.2023
Tilføjet 7.12.2023
Abstract Background The severity of coronavirus disease 2019 (COVID-19) infections has led to the development of several therapeutic agents, with tocilizumab becoming increasingly used to treat patients with COVID-19-related pneumonia. This study compared the use of tocilizumab treatment with the standard of care (SOC) to determine its efficacy against severe COVID-19-related pneumonia in Japan. Methods This retrospective cohort study was designed to evaluate the efficacy of tocilizumab in two different databases: the JA42434 single-arm study and COVID-19 Registry Japan (COVIREGI-JP), with a synthetic control group from the COVIREGI-JP cohort as a benchmark for the tocilizumab group. The study’s primary objective was to evaluate the efficacy of tocilizumab in treating severe COVID-19-related pneumonia compared to the SOC among patients included in the above two databases. The SOC group was extracted as the synthetic control group using exact matching and a propensity score matching in sequence per subject. As a secondary objective, the efficacy of tocilizumab compared to the SOC was evaluated exclusively among patients included in the COVIREGI-JP database. In each objective, the primary endpoint was defined as the time to discharge or the status of awaiting discharge. Results For the primary endpoint, the hazard ratio (HR) of the tocilizumab group against the SOC group was 1.070 (95% confidence interval [CI]: 0.565–2.028). The median time from Study Day 1 to discharge or the state of awaiting discharge was 15 days in the tocilizumab group and 16 days in the SOC group. The HRs for the secondary endpoints, namely, time to improvement in the clinical state, time to clinical failure, and time to recovery, were 1.112 (95% CI: 0.596–2.075), 0.628 (95% CI: 0.202–1.953), and 1.019 (95% CI: 0.555–1.871), respectively. Similarly, the HR of the primary endpoint for the secondary objective was 0.846 (95% CI: 0.582–1.230). Conclusions Tocilizumab did not demonstrate a positive effect on time to discharge or the state of awaiting discharge. Furthermore, no statistically significant differences in other clinical outcomes, such as time to improvement in the clinical state, time to clinical failure, and time to recovery, were observed among the groups.
Læs mere Tjek på PubMedJournal of the American Medical Association, 6.12.2023
Tilføjet 6.12.2023
To the Editor We have several comments about the recent randomized clinical trial (ACTIV-1) that investigated the effect of abatacept, cenicriviroc, or infliximab on COVID-19 pneumonia.
Læs mere Tjek på PubMedJournal of the American Medical Association, 6.12.2023
Tilføjet 6.12.2023
In Reply We thank Drs Mathew and Feldmann for their comments on the results of ACTIV-1. We agree that mortality is a very important clinical outcome, but designing a trial such as ACTIV-1 to have sufficient power to detect an effect on mortality was challenging in June 2020, when data on clinical outcomes of severe COVID-19 were in flux. Indeed, the design of ACTIV-1 was heavily influenced by the results of ACTT-1, the initial placebo-controlled trial of remdesivir, which showed evidence of improved time to recovery but not improved mortality.
Læs mere Tjek på PubMedClinical Infectious Diseases, 5.12.2023
Tilføjet 5.12.2023
AbstractBackgroundMetallo-β-lactamases (MBL)-producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments and outcomes of infections by MBL-Enterobacterales.MethodsProspective observational study conducted in the Pisa University Hospital (Jan 2019-Oct 2022) including patients with MBL-producing Enterobacterales infections. The primary outcome measure was 30-day mortality. A multivariable Cox regression analysis was performed to identify factors associated with 30-day mortality. Adjusted hazard ratio (aHR) (95% confidence intervals, CI) were calculated.Results343 patients were included: 15 VIM- and 328 NDM-producing Enterobacterales infections. Overall, 199 (58%) were bloodstream infections, 60 (17.5%) hospital-acquired/ventilator-associated pneumonias, 60 (17.5%) complicated urinary tract infections, 13 (3.8%) intra-abdominal infections, 11 (3.2%) skin and soft tissue infections. Thirty-day mortality was 29.7%. Thirty-two patients did not receive in vitro active antibiotic therapy, 215/343 (62.7%) received ceftazidime-avibactam (CZA) plus aztreonam (ATM), 33/343 (9.6%) cefiderocol-containing regimens, 26/343 (7.6%) colistin-containing regimens and 37 (10.8%) other active antibiotics. On multivariable analysis, septic shock (aHR 3.57, 95% CI 2.05-6.23, p
Læs mere Tjek på PubMedBMC Infectious Diseases, 4.12.2023
Tilføjet 4.12.2023
Abstract Background The severity of coronavirus disease 2019 (COVID-19) infections has led to the development of several therapeutic agents, with tocilizumab becoming increasingly used to treat patients with COVID-19-related pneumonia. This study compared the use of tocilizumab treatment with the standard of care (SOC) to determine its efficacy against severe COVID-19-related pneumonia in Japan. Methods This retrospective cohort study was designed to evaluate the efficacy of tocilizumab in two different databases: the JA42434 single-arm study and COVID-19 Registry Japan (COVIREGI-JP), with a synthetic control group from the COVIREGI-JP cohort as a benchmark for the tocilizumab group. The study’s primary objective was to evaluate the efficacy of tocilizumab in treating severe COVID-19-related pneumonia compared to the SOC among patients included in the above two databases. The SOC group was extracted as the synthetic control group using exact matching and a propensity score matching in sequence per subject. As a secondary objective, the efficacy of tocilizumab compared to the SOC was evaluated exclusively among patients included in the COVIREGI-JP database. In each objective, the primary endpoint was defined as the time to discharge or the status of awaiting discharge. Results For the primary endpoint, the hazard ratio (HR) of the tocilizumab group against the SOC group was 1.070 (95% confidence interval [CI]: 0.565–2.028). The median time from Study Day 1 to discharge or the state of awaiting discharge was 15 days in the tocilizumab group and 16 days in the SOC group. The HRs for the secondary endpoints, namely, time to improvement in the clinical state, time to clinical failure, and time to recovery, were 1.112 (95% CI: 0.596–2.075), 0.628 (95% CI: 0.202–1.953), and 1.019 (95% CI: 0.555–1.871), respectively. Similarly, the HR of the primary endpoint for the secondary objective was 0.846 (95% CI: 0.582–1.230). Conclusions Tocilizumab did not demonstrate a positive effect on time to discharge or the state of awaiting discharge. Furthermore, no statistically significant differences in other clinical outcomes, such as time to improvement in the clinical state, time to clinical failure, and time to recovery, were observed among the groups.
Læs mere Tjek på PubMedBMC Infectious Diseases, 3.12.2023
Tilføjet 3.12.2023
Abstract Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.
Læs mere Tjek på PubMedBMC Infectious Diseases, 3.12.2023
Tilføjet 3.12.2023
Abstract We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV.
Læs mere Tjek på PubMedBMC Infectious Diseases, 3.12.2023
Tilføjet 3.12.2023
Abstract Background The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country’s epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters’ predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). Methods A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. Results Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P
Læs mere Tjek på PubMedBMC Infectious Diseases, 3.12.2023
Tilføjet 3.12.2023
Abstract Objective Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. Methods A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. Results Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. Conclusion The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Læs mere Tjek på PubMedBMC Infectious Diseases, 3.12.2023
Tilføjet 3.12.2023
Abstract Background We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. Methods This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline’s clinical efficacy and safety were performed to control confounding factors. Results For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. Conclusions Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient’s age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.
Læs mere Tjek på PubMedPo‐Yu Huang, Chih‐Cheng Lai, Chi‐Kuei Hsu
Journal of Medical Virology, 2.12.2023
Tilføjet 2.12.2023
Avantika Nathani, Anoosha Tauquir, Safdar Khan, Andrea Valeria Arrossi, Francisco Almeida
American Journal of Respiratory and Critical Care Medicine , 2.12.2023
Tilføjet 2.12.2023
American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page e44-e46, December 1, 2023.
Læs mere Tjek på PubMedBMC Infectious Diseases, 1.12.2023
Tilføjet 1.12.2023
Abstract Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection.
Læs mere Tjek på PubMedMizan Kindu, Feleke Moges, Degu Ashagrie, Zemene Tigabu, Baye Gelaw
PLoS One Infectious Diseases, 30.11.2023
Tilføjet 30.11.2023
by Mizan Kindu, Feleke Moges, Degu Ashagrie, Zemene Tigabu, Baye Gelaw Background Intensive care units are units where healthcare-associated infections (HAIs) are common and antimicrobial resistance rates are increasing. Microbial contamination in hospital environment plays an important role in the development of HAIs. Intervention-based improvements in infection prevention and control at national and facility level are critical for the containment of antimicrobial resistance and prevention of HAIs. Objectives This study aimed to determine the distribution of multidrug-resistant and carbapenemase-producing critical gram negative bacteria (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter species) and their antibiotic resistance in intensive care unit environmental surfaces at the University of Gondar and Felege Hiwot Comprehensive Specialized Hospitals. Methods This was multicenter hospital-based cross sectional study. Environmental samples were swabbed from all intensive care units using a normal saline moistened-sterile cotton tip stick. Bacteria culturing and antibiotic susceptibility testing were performed following standard microbiological techniques. Selected meropenem-resistant isolates were phenotypically assessed for carbapenemase production using modified and simplified carbapenem inactivation methods. Results From a total of 384 environmental samples analyzed, 126 (32.8%) showed growth and 162 isolates were identified. K. pneumoniae (79/162, 48.8%) was the commonest isolate followed by Acinetobacter species (51/162, 31.5%), E. coli (19/162, 11.7%) and P. aeruginosa (13/162, 8.0%). Multidrug-resistant and carbapenemase-producing isolates were detected on most hospital environment surface types, especially from the baby bed sets and incubators. The most common multidrug-resistant and principal carbapenemase producer was K. pneumoniae, with rates of 71(89.9%) and 24(85.7%), respectively. Conclusion This study revealed the distribution of multidrug-resistant and carbapenemase-producing critical gram negative bacteria in the environment of intensive care unit. Higher detection rate of multidrug-resistant and carbapenemase-producing K. pneumoniae on most environmental surfaces calls for urgent control action and further attention.
Læs mere Tjek på PubMedBMC Infectious Diseases, 30.11.2023
Tilføjet 30.11.2023
Abstract We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV.
Læs mere Tjek på PubMedJiankang ZhaoDanni PuZiyao LiXinmeng LiuYulin ZhangYongli WuFeilong ZhangChen LiXianxia ZhuoBinghuai LuBin Cao1National Center for Respiratory Medicine, Beijing, China2Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China3State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, China4National Clinical Research Center for Respiratory Diseases, Beijing, China5Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China6Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China7Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China8Liuyang Traditional Chinese Medicine Hospital, Changsha, Hunan, China9Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China10Department of Respiratory Medicine, Capital Medical University, Beijing, China, Alessandra Carattoli
Antimicrobial Agents And Chemotherapy, 28.11.2023
Tilføjet 28.11.2023
BMC Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
Abstract Background The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country’s epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters’ predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). Methods A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. Results Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P
Læs mere Tjek på PubMedBMC Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
Abstract Objective Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. Methods A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. Results Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. Conclusion The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent.
Læs mere Tjek på PubMedBMC Infectious Diseases, 28.11.2023
Tilføjet 28.11.2023
Abstract Background We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. Methods This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline’s clinical efficacy and safety were performed to control confounding factors. Results For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. Conclusions Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient’s age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.
Læs mere Tjek på PubMedLiang En Wee, David Chien Lye, Vernon Lee
Lancet Respiratory Medicine, 28.11.2023
Tilføjet 28.11.2023
Despite decades of advances in clinical management protocols and new antibiotics, pneumonia continues to be a leading cause of morbidity and mortality worldwide. The 2019 Global Burden of Disease Study indicated that lower respiratory infections, including pneumonia, were the fourth leading cause of disability-adjusted life-years across all ages.1 People at the extremes of age, specifically children younger than 10 years and older adults (aged ≥75 years), had the highest burden of lower respiratory infections.
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