ABSTRACT
BACKGROUND: Bloodstream infections (BSIs) due to Enterococcus faecium (E. faecium), particularly those due to vancomycin-resistant enterococcus (VRE), are still a therapeutic challenge. AIM: To evaluate mortality from BSI due to E. faecium and VRE in central Taiwan. MATERIALS AND METHODS: We retrospectively analyzed cases of significant E. faecium BSI in the Changhua Christian Hospital System between January 1, 2010 and December 31, 2013. RESULTS: Of the 76 cases, 28 patients (36.8%) were admitted to intensive care units (ICUs) at the onset of BSI, 10 (13.2%) cases were associated with polymicrobial bacteremia, and 29 (38.2%) cases were associated with entry via the biliary tract. VRE was observed in 18 (23.7%) cases. The 30-day mortality rate was 13.1% (10/76). Multivariate logistic regression analysis showed that bacteremia of non-biliary tract origin (OR = 8.43, 95% confidence interval (95% CI) = 1.32-54.00, p = 0.002) and ICU admission (OR = 4.2, 95% CI = 1.7-10.0, p = 0.002) were significant risk factors for 30-day mortality, whereas appropriate antimicrobial therapy was a protective factor for 30-day mortality (OR = 0.33, 95% CI = 0.14-0.79, p = 0.013). CONCLUSIONS: Our results underscore the need to assist patients admitted to ICUs with E. faecium BSIs with a non-biliary tract origin. We emphasize the use of appropriate antimicrobial therapy for E. faecium BSI with the aim to rescue more patients with these infections.
Subject(s)
Bacteremia/microbiology , Bacteremia/mortality , Vancomycin-Resistant Enterococci/isolation & purification , Bacteremia/drug therapy , Female , Humans , Incidence , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Risk Factors , Taiwan/epidemiology , Vancomycin ResistanceABSTRACT
Background: Bloodstream infections (BSIs) due to Enterococcus faecium (E. faecium), particularly those due to vancomycin-resistant enterococcus (VRE), are still a therapeutic challenge. Aim: To evaluate mortality from BSI due to E. faecium and VRE in central Taiwan. Materials and Methods: We retrospectively analyzed cases of significant E. faecium BSI in the Changhua Christian Hospital System between January 1, 2010 and December 31, 2013. Results: Of the 76 cases, 28 patients (36.8%) were admitted to intensive care units (ICUs) at the onset of BSI, 10 (13.2%) cases were associated with polymicrobial bacteremia, and 29 (38.2%) cases were associated with entry via the biliary tract. VRE was observed in 18 (23.7%) cases. The 30-day mortality rate was 13.1% (10/76). Multivariate logistic regression analysis showed that bacteremia of non-biliary tract origin (OR = 8.43, 95% confidence interval (95% CI) = 1.32-54.00, p = 0.002) and ICU admission (OR = 4.2, 95% CI = 1.7-10.0, p = 0.002) were significant risk factors for 30-day mortality, whereas appropriate antimicrobial therapy was a protective factor for 30-day mortality (OR = 0.33, 95% CI = 0.14-0.79, p = 0.013). Conclusions: Our results underscore the need to assist patients admitted to ICUs with E. faecium BSIs with a non-biliary tract origin. We emphasize the use of appropriate antimicrobial therapy for E. faecium BSI with the aim to rescue more patients with these infections.
Antecedentes: Las infecciones del torrente sanguíneo por Enterococcus faecium, particularmente aquellas causadas por enterococos resistentes a vancomicina (ERV), representan aún un desafío para los tratamientos. Este estudio está orientado a la evaluación de la mortalidad debido a la infección del torrente sanguíneo (ITS) por E. faecium y por enterococos resistentes a vancomicina (ERV) en Taiwán central. Materiales y Métodos: Analizamos de forma retrospectiva casos de ITS causadas por E. faecium genuinas en el Sistema del Hospital Changhua Christian, entre los días 1 de enero de 2010 y 31 de diciembre de 2013. Resultados: De los 76 casos analizados, 28 pacientes fueron ingresados a las Unidades de Cuidados Intensivos (UCI) al comienzo de una ITS (36,8%), 10 casos fueron asociados a bacteriemia polimicrobiana (13,2%), y 29 casos tuvieron como puerta de entrada la vía biliar. En 18 casos se pudieron observar ERV (23,7%). La mortalidad a 30 días fue de 13,1% (10/76). El análisis multivariado mediante regresión logística mostró que la bacteriemia de origen no biliar (OR = 8,43, 95% intervalo de confianza (95% CI) = 1,32-54,00; p = 0,002), y el ingreso a la UCI (OR = 4,2; 95% CI = 1,7-10,0; p = 0,002), fueron factores de riesgo significativos para el rango de mortalidad de 30 días, así como un tratamiento de antimicrobiano apropiado constituye un factor protector en contra la mortalidad (OR = 0,33; 95% CI = 0,14-0,79; p = 0,013). Conclusiones: Nuestros resultados destacan la necesidad de asistir a los pacientes ingresados a la UCI con ITS por E. faecium con origen no biliar. Hacemos énfasis a la aplicación de una antibioterapia adecuada para sacar adelante a un mayor número de pacientes con este tipo de infecciones.
Subject(s)
Humans , Male , Female , Middle Aged , Bacteremia/microbiology , Bacteremia/mortality , Vancomycin-Resistant Enterococci/isolation & purification , Taiwan/epidemiology , Microbial Sensitivity Tests , Incidence , Retrospective Studies , Risk Factors , Bacteremia/drug therapy , Vancomycin ResistanceABSTRACT
Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenviroment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal cells were decreased. When HIF-1α was blocked, the co-cultured Jurkat cell’s adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.
Subject(s)
Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Leukemia, T-Cell/metabolism , Mesenchymal Stem Cells/metabolism , Cell Adhesion , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Jurkat Cells , Real-Time Polymerase Chain ReactionABSTRACT
Hypoxia inducible factor-1α (HIF-1α) is an important transcription factor, which plays a critical role in the formation of solid tumor and its microenvironment. The objective of the present study was to evaluate the expression and function of HIF-1α in human leukemia bone marrow stromal cells (BMSCs) and to identify the downstream targets of HIF-1α. HIF-1α expression was detected at both the RNA and protein levels using real-time PCR and immunohistochemistry, respectively. Vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) were detected in stromal cells by enzyme-linked immunosorbent assay. HIF-1α was blocked by constructing the lentiviral RNAi vector system and infecting the BMSCs. The Jurkat cell/BMSC co-cultured system was constructed by putting the two cells into the same suitable cultured media and conditions. Cell adhesion and secretion functions of stromal cells were evaluated after transfection with the lentiviral RNAi vector of HIF-1α. Increased HIF-1α mRNA and protein was detected in the nucleus of the acute myeloblastic and acute lymphoblastic leukemia compared with normal BMSCs. The lentiviral RANi vector for HIF-1α was successfully constructed and was applied to block the expression of HIF-1α. When HIF-1α of BMSCs was blocked, the expression of VEGF and SDF-1 secreted by stromal cells were decreased. When HIF-1α was blocked, the co-cultured Jurkat cell's adhesion and migration functions were also decreased. Taken together, these results suggest that HIF-1α acts as an important transcription factor and can significantly affect the secretion and adhesion functions of leukemia BMSCs.
Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Leukemia, T-Cell/metabolism , Mesenchymal Stem Cells/metabolism , Cell Adhesion , Enzyme-Linked Immunosorbent Assay , Humans , Immunohistochemistry , Jurkat Cells , Real-Time Polymerase Chain ReactionABSTRACT
Antibacterial monomers incorporated in dentin bonding systems may have toxic effects on the pulp. Thus, the cytotoxicity of antibacterial monomers and its underlying mechanisms must be elucidated to improve the safety of antibacterial monomer application. The influence of an antibacterial monomer, methacryloxylethyl cetyl ammonium chloride (DMAE-CB), on the vitality of L929 mouse fibroblasts was tested using MTT assay. Cell cycle progression was studied using flow cytometry. Production of intracellular reactive oxygen species (ROS) after DMAE-CB treatment was measured using 2,7-dichlorodihydrofluorescein diacetate staining and flow cytometry analysis. Loss of mitochondrial membrane potential, disturbance of Bcl-2 and Bax expression, as well as release of cytochrome C were also measured using flow cytometry analysis or Western blot to explore the possible involvement of the mitochondrial-related apoptotic pathway. DMAE-CB elicited cell death in a dose-dependent manner and more than 50 percent of cells were killed after treatment with 30 µM of the monomer. Both necrosis and apoptosis were observed. DMAE-CB also induced G1- and G2-phase arrest. Increased levels of intracellular ROS were observed after 1 h and this overproduction was further enhanced by 6-h treatment with the monomer. DMAE-CB may cause apoptosis by disturbing the expression of Bcl-2 and Bax, reducing the mitochondrial potential and inducing release of cytochrome C. Taken together, these findings suggest that the toxicity of the antibacterial monomer DMAE-CB is associated with ROS production, mitochondrial dysfunction, cell cycle disturbance, and cell apoptosis/necrosis.
Subject(s)
Animals , Mice , Anti-Bacterial Agents/toxicity , Apoptosis/drug effects , Dentin-Bonding Agents/toxicity , Methacrylates/toxicity , Mitochondria/drug effects , Oxidative Stress/drug effects , Quaternary Ammonium Compounds/toxicity , Analysis of Variance , Fibroblasts/drug effects , Models, Animal , Reactive Oxygen Species/metabolism , Statistics, NonparametricABSTRACT
Bat coronaviruses (Bt-CoVs) are thought to be the precursors of severe acute respiratory syndrome coronavirus. We detected Bt-CoVs in 2 bat species from Trinidad. Phylogenetic analysis of the RNA-dependent RNA polymerase gene and helicase confirmed them as group 1 coronaviruses.