Маркеры воспаления при атеросклеротических изменениях сосудистой стенки у пациентов с ишемической болезнью сердца

ишемическая болезнь сердцаатеросклерозцитокин

Analytical Performance and Potential Clinical Utility of EUCAST Rapid Antimicrobial Susceptibility Testing in Blood Cultures after Four Hours of Incubation

EUCAST rapid antimicrobial susceptibility testing (RAST) provides antibiotic susceptibility results after 4 to 8 h of incubation. This study assessed the diagnostic performance and clinical usefulness of EUCAST RAST after 4 h. This was a retrospective clinical study performed on blood cultures with Escherichia coli and Klebsiella pneumoniae complex (K. pneumoniae and Klebsiella variicola) at Karolinska University Laboratory (Stockholm, Sweden). The rate of categorized RAST results and the categorical agreement (CA) of RAST with the standard EUCAST 16-to-20-h disk diffusion (DD) method for piperacillin-tazobactam, cefotaxime, ceftazidime, meropenem, and ciprofloxacin were analyzed, as well as the utility of RAST for adjusting the empirical antibiotic therapy (EAT) and the combination of RAST with a lateral flow assay (LFA) for extended-spectrum beta-lactamase (ESBL) detection. A total of 530 E. coli and 112 K. pneumoniae complex strains were analyzed, generating 2,641 and 558 readable RAST zones, respectively. RAST results categorized according to antimicrobial sensitivity/resistance (S/R) were obtained for 83.1% (2,194/2,641) and 87.5% (488/558) of E. coli and K. pneumoniae complex strains, respectively. The RAST result categorization to S/R for piperacillin-tazobactam was poor (37.2% for E. coli and 66.1% for K. pneumoniae complex). CA with the standard DD method was over 97% for all tested antibiotics. Using RAST, we detected 15/26 and 1/10 of the E. coli and K. pneumoniae complex strains that were resistant to the EAT. For patients treated with cefotaxime, RAST was used to detect 13/14 cefotaxime-resistant E. coli strains and 1/1 cefotaxime-resistant K. pneumoniae complex strain. ESBL positivity was reported the same day as blood culture positivity with RAST and LFA. EUCAST RAST provides accurate and clinically relevant susceptibility results after 4 h of incubation and can accelerate the assessment of resistance patterns.IMPORTANCE Early effective antimicrobial treatment has been shown to be crucial for improving the outcome of bloodstream infections (BSI) and sepsis. In combination with the rise of antibiotic resistance, this calls for accelerated methods for antibiotic susceptibility testing (AST) for effective treatment of BSI. This study assesses EUCAST RAST, an AST method that yields results in 4, 6, or 8 h after blood culture positivity. We analyzed a high number of clinical samples of Escherichia coli and Klebsiella pneumoniae complex strains and confirm that the method delivers reliable results after 4 h of incubation for the relevant antibiotics for treating E. coli and K. pneumoniae complex bacteremia. Furthermore, we conclude that it is an important tool for antibiotic treatment decision-making and early detection of ESBL-producing isolates. Early effective antimicrobial treatment has been shown to be crucial for improving the outcome of bloodstream infections (BSI) and sepsis. In combination with the rise of antibiotic resistance, this calls for accelerated methods for antibiotic susceptibility testing (AST) for effective treatment of BSI.Funding Agencies|Karolinska Institutet</p

Secondary bacterial infections and antimicrobial resistance in COVID-19: comparative evaluation of pre-pandemic and pandemic-era, a retrospective single center study

Purpose In this study, we aimed to evaluate the epidemiology and antimicrobial resistance (AMR) patterns of bacterial pathogens in COVID-19 patients and to compare the results with control groups from the pre-pandemic and pandemic era. Methods Microbiological database records of all the COVID-19 diagnosed patients in the Ege University Hospital between March 15, 2020, and June 15, 2020, evaluated retrospectively. Patients who acquired secondary bacterial infections (SBIs) and bacterial co-infections were analyzed. Etiology and AMR data of the bacterial infections were collected. Results were also compared to control groups from pre-pandemic and pandemic era data. Results In total, 4859 positive culture results from 3532 patients were analyzed. Fifty-two (3.59%) patients had 78 SBIs and 38 (2.62%) patients had 45 bacterial co-infections among 1447 COVID-19 patients. 22/85 (25.88%) patients died who had bacterial infections. The respiratory culture-positive sample rate was 39.02% among all culture-positive samples in the COVID-19 group. There was a significant decrease in extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (8.94%) compared to samples from the pre-pandemic (20.76%) and pandemic era (20.74%) (p = 0.001 for both comparisons). Interestingly, Acinetobacter baumannii was the main pathogen in the respiratory infections of COVID-19 patients (9.76%) and the rate was significantly higher than pre-pandemic (3.49%, p < 0.002) and pandemic era control groups (3.11%, p < 0.001). Conclusion Due to the low frequency of SBIs reported during the ongoing pandemic, a more careful and targeted antimicrobial prescription should be taken. While patients with COVID-19 had lower levels of ESBL-producing Enterobacterales, the frequency of multidrug-resistant (MDR) A. baumannii is higher.Karolinska InstituteOpen access funding provided by Karolinska Institute. The author(s) received no specific funding for this work

Monocyte-derived dendritic cells express and secrete matrix-degrading metalloproteinases and their inhibitors and are imbalanced in multiple sclerosis

Dendritic cells (DC) are antigen-presenting cells (APC) that most efficiently initiate and control immune responses. Migration processes of blood DC are crucial to exert their professional antigen-presenting functions. Matrix-degrading metalloproteinases (MMP) are proteolytic enzymes, which are considered to be key enzymes in extracellular matrix (ECM) turnover and mediators of cell migration. Tissue inhibitors of metalloproteinases (TIMP) are important regulators of MMP activity. Here we investigate whether blood monocyte-derived immature DC (iDC) and mature DC (mDC) express, produce and secrete functionally active MMP-1, -2, -3 and -9 and their inhibitors TIMP-1 and -2, and examine their involvement in multiple sclerosis (MS). On mRNA level, we observed high numbers of MMP-2 and TIMP-2 mRNA expressing iDC in MS. On protein level, high percentages of MMP-1, -2 and -9 expressing iDC by flow cytometry, and high MMP-1 secretion by Western blot together with high MMP-2 and -9 activities in iDC supernatants as studied with zymography were observed. Similarly, MS is associated with high percentages of MMP-2 and -3 and of TIMP-1 expressing mDC by flow cytometry together with high MMP-3 secretion and high MMP-9 activity in culture supernatants. Spontaneous migratory capacity of both iDC and mDC over ECM-coated filters was higher in MS compared to healthy controls (HC). In conclusion, blood monocyte-derived iDC and mDC express, produce and secrete several MMP and TIMP. Alterations in these molecules as observed in MS may be functionally important for DC functioning

Evaluation of an extracorporeal ozone-based bactericide system for the treatment of Escherichia coli sepsis

Background: Sepsis is associated with substantial mortality rates. Antibiotic treatment is crucial, but global antibiotic resistance is now classified as one of the top ten global public health risks facing humanity. Ozone (O-3) is an inorganic molecule with no evident function in the body. We investigated the bactericide properties of ozone, using a novel system of extracorporeal ozone blood treatment. We hypothesized that ozone would decrease the concentration of viable Escherichia coli (E. coli) in human whole blood and that the system would be technically feasible and physiologically tolerable in a clinically relevant model of E. coli sepsis in swine. Methods: The E. coli strain B09-11822, a clinical isolate from a patient with septic shock was used. The in vitro study treated E. coli infected human whole blood (n = 6) with ozone. The in vivo 3.5-h sepsis model randomized swine to E. coli infusion and ozone treatment (n = 5) or E. coli infusion and no ozone treatment (n = 5). Live E. coli, 5 x 10(7) colony-forming units (CFU/mL) was infused in a peripheral vein. Ozone treatment was initiated with a duration of 30 min after 1.5 h. Results: The single pass in vitro treatment decreased E. coli by 27%, mean 1941 to 1422 CFU/mL, mean of differences - 519.0 (95% CI - 955.0 to - 82.98,P= 0.0281). pO(2) increased (95% CI 31.35 to 48.80, P= 0.0007), pCO(2) decreased (95% CI -3.203 to - 1.134, P= 0.0069), oxyhemoglobin increased (95% CI 1.010 to 3.669, P= 0.0113). Methemoglobin was not affected. In the sepsis model, 9/10 swine survived. One swine randomized to ozone treatment died from septic shock before initiation of the treatment. Circulatory, respiratory, and metabolic parameters were not affected by the ozone treatment. E. coli in arterial blood, in organs and in aerobic and anaerobic blood cultures did not differ. Hemoglobin, leucocytes, and methemoglobin were not affected by the treatment. Conclusions: Ozone decreased the concentration of viable E. coli in human whole blood. The system was technically feasible and physiologically tolerable in porcine sepsis/septic shock and should be considered for further studies towards clinical applications

ECMM CandiReg-A ready to use platform for outbreaks and epidemiological studies

BACKGROUND: Recent outbreaks of Candida auris further exemplify that invasive Candida infections are a substantial threat to patients and healthcare systems. Even short treatment delays are associated with higher mortality rates. Epidemiological shifts towards more resistant Candida spp. require careful surveillance. OBJECTIVES: Triggered by the emergence of C auris and by increasing antifungal resistance rates the European Confederation of Medical Mycology developed an international Candida Registry (FungiScope™ CandiReg) to allow contemporary multinational surveillance. METHODS: CandiReg serves as platform for international cooperation to enhance research regarding invasive Candida infections. CandiReg uses the General Data Protection Regulation compliant data platform ClinicalSurveys.net that holds the electronic case report forms (eCRF). Data entry is supported via an interactive macro created by the software that can be accessed via any Internet browser. RESULTS: CandiReg provides an eCRF for invasive Candida infections that can be used for a variety of studies from cohort studies on attributable mortality to evaluations of guideline adherence, offering to the investigators of the 28 ECMM member countries the opportunity to document their cases of invasive Candida infection. CandiReg allows the monitoring of epidemiology of invasive Candida infections, including monitoring of multinational outbreaks. Here, we describe the structure and management of the CandiReg platform. CONCLUSION: CandiReg supports the collection of clinical information and isolates to improve the knowledge on epidemiology and eventually to improve management of invasive Candida infections. CandiReg promotes international collaboration, improving the availability and quality of evidence on invasive Candida infection and contributes to improved patient management.status: publishe