Patrones de resistencia a antibióticos de Acinetobacter baumannii en un hospital de Colombia

Objetivo: Identificar patrones de resistencia en los aislamientos de A. baumannii obtenidos en una unidad de cuidados intensivos de Cali, Colombia. Diseño: Estudio descriptivo, prospectivo de corte transversal. Institución: Clínica Universitaria Rafael Uribe Uribe, Cali, Colombia. Materiales: Los aislamientos se obtuvieron de cultivos de muestras de sangre, heridas quirúrgicas, secreción nasal, orina, secreción uretral y puntas de catéter. Intervenciones: Se recolectaron 52 aislamientos durante los años 2009 y 2010. Mediante el análisis del antibiograma se identificaron patrones de resistencia (antibiotipos), se realizó antibiograma cuantitativo y se construyó un cladograma basado en el agrupamiento por el método de promedios aritméticos de grupos apareados no ponderados (conocido en inglés como UPGMA). Principales medidas de resultados: Medida de la concentración mínima inhibitoria (CMI) y el coeficiente de similitud generado por las distancias de los diámetros de los halos de inhibición entre dos aislamientos (antibiograma cuantitativo). Resultados: Se identificaron 5 antibiotipos; el 50% de los aislamientos se agruparon en el antibiotipo 1, con resistencia a todos los antibióticos y sensibilidad a tigeciclina y sulperazona; el antibiotipo 4 agrupó los aislamientos con resistencia a todos los antibióticos (19,3%). En el antibiograma cuantitativo se identificó dos clados con 5 y 47 aislamientos, respectivamente. Conclusiones: Los aislamientos de Acinetobacter baumannii tuvieron pocas diferencias fenotípicas y es probable que presenten alguna de las β-lactamasas tipo OXA

Epidemiología de bacterias nosocomiales resistentes a los antimicrobianos

Nosocomial infections are a major challenge for public health because of the high rates of morbidity and mortality generated. It was considered that the excessive or inappropriate use of antibiotics triggers the emergence of resistant strains. Among the clinically important bacteria that most commonly cause nososcomial infections, Gram positive multiresistant pathogens stand out such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp (VRE), and the Gram negative strains of Klebsiella pneumoniae, Escherichia coli, Pseudomonas spp. and Acinetobacter baumannii producing expanded spectrum β-lactamases (ESβL). This review describes the behavior of the main bacterial pathogens resistant to antibiotics that cause infections in Europe, United States, and Latin America, emphasizing studies of molecular epidemiology on a global scale, including the major epidemiological studies in Colombia. The genetic structure of S. aureus and Enterococcus spp strains shows a clonal characteristic favored by the predominance of a small number of clones with the capacity to spread globally, due probably to cross-infection. However, the introduction of MRSA strains from the community encourages genetic diversity, tending to establish a genetic polyclonal endemic structure in places like the United States. In Gram negative bacteria, the high genetic diversity among isolates, mainly in Latin American countries, indicates that the polyclonal spread is influenced by horizontal transfer of plasmids, by excessive exposure to antibiotics, and prolonged hospital stays. In Colombia, there is information on nosocomial resistant pathogens, but molecular epidemiological information is still scarce. Las infecciones nosocomiales constituyen un gran desafío para la salud pública por las altas tasas de morbilidad y mortalidad que generan. Se ha considerado que el uso inapropiado o excesivo de antibióticos desencadena la aparición de cepas resistentes. Entre las bacterias de importancia clínica que con mayor frecuencia causan infecciones nososcomiales, se destacan los patógenos Gram positivos multiresistentes como Staphylococcus aureus con resistencia a meticilina (SARM) y Enterococcus spp. resistentes a vancomicina (ERV). En los Gram negativos, hay resistencia sobre todo con las cepas de Klebsiella pneumoniae, Escherichia coli, Pseudomonas spp. y Acinetobacter baumannii productoras de β-lactamasas de espectro extendido (BLEEs, en inglés: ESβL expanded spectrum β-lactamases). Esta revisión tiene como finalidad realizar una decripción del estado de la resistencia bacteriana a los antibióticos en los principales patógenos que causan infecciones nosocomiales en países de Europa, Estados Unidos y de Latinoamérica, destacando los estudios de epidemiología molecular a escala global e incluyendo los principales estudios epidemiológicos realizados en Colombia. La estructura genética de las cepas de Staphylococus aureus y Enterococcus spp. evidencia una característica clonal favorecida por el predominio de un número pequeño de clones con capacidad de diseminarse en forma global, debida probablemente a infecciones cruzadas. Sin embargo, la introducción de cepas SARM desde la comunidad está favoreciendo la diversidad genética, tendiendo a establecerse una estructura genética policlonal en lugares endémicos como los Estados Unidos. En las bacterias Gram negativas, se destaca una alta diversidad genética entre los aislados, sobre todo en países de Latinoamérica, indicando que la diseminación sigue una estructura genética policlonal, influida por la transferencia horizontal de plasmidos, por la excesiva exposición a antibióticos y una estancia hospitalaria prolongada. En Colombia se dispone de información sobre los patógenos nosocomiales resistentes, pero la información epidemiológica molecular aún es escasa

BIM en la construcción

244 páginas.En la actualidad, con la metodología BIM (Building Information Modeling), todos los sistemas de información de los procesos productivos en la obra se han integrado, la información se puede compartir a distancia y en tiempo real con todos los actores involucrados en el proyecto. En estas condiciones, las instituciones generadoras de obras y las empresas prestadoras de servicios se están rediseñando con nuevos modelos de negocios enfocados en satisfacer las actuales demandas y experiencias de los clientes. El libro que aquí se presenta reúne el trabajo de investigación referente a BIM de la Red Académica de Diseño Construcción integrada por académicos de la Facultad de Ingeniería de la Universidad Autónoma de Yucatán, México (UADY), el Worcester Polytechnical Institute (WPI) de Massachusetts, Estados Unidos y del Área de Administración y Tecnología para el Diseño de la Universidad Autónoma Metropolitana, Unidad Azcapotzalco (UAM). También han colaborado con la Red investigadores de la Universidad Politécnica de Madrid (UPM), España y, dentro de la UAM, académicos de la División de Ciencias Básicas e Ingeniería, Departamento de Materiales, del Área de Construcción. Cabe mencionar que los artículos ya han sido publicados con anterioridad en los Anuarios de Administración y Tecnología para el Diseño y las Compilaciones de Artículos de Investigación en Administración y Tecnología para la Arquitectura, Diseño e Ingeniería, productos del trabajo de investigación del Área que edita anualmente desde 1999, como se indica en el índice del presente libro

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19.This study has been funded by Pharmamar, S.A. (Madrid, Spain). This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N.I.U. has non-restrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. N.J.K. was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between UCSF, UCB, and GSK (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by CRIP (Center for Research for Influenza Pathogenesis), a NIAID supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972 and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to AG-S. S.Y. received funding from a Swiss National Foundation (SNF) Early Postdoc Mobility fellowship (P2GEP3_184202).N

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.This work was supported by grants from the Government of Spain (PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E043). The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. We also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). N Izquierdo-Useros has nonrestrictive funding from PharmaMar to study the antiviral effect of Plitidepsin. NJ Krogan was funded by grants from the National Institutes of Health (P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302); by the Excellence in Research Award (ERA) from the Laboratory for Genomics Research (LGR), a collaboration between the University of California, San Francisco (UCSF), University of California, Berkley (UCB), and GlaxoSmithKline (GSK) (#133122P); by the Roddenberry Foundation, and gifts from QCRG philanthropic donors. This work was supported by the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement #HR0011-19-2-0020. The views, opinions, and/or findings contained in this material are those of the authors and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. This research was partly funded by Center for Research for Influenza Pathogenesis and Transmission (CRIPT), a National Institute of Allergy and Infectious Diseases (NIAID) supported Center of Excellence for Influenza Research and Response (CEIRS, contract # 75N93021C00014), by DARPA grant HR0011-19-2-0020, by supplements to NIAID grants U19AI142733, U19AI135972, and DoD grant W81XWH-20-1-0270, and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)), and anonymous donors to A García-Sastre. S Yildiz received funding from a Swiss National Foundation Early Postdoc Mobility fellowship (P2GEP3_184202).Peer reviewe

Patrones de resistencia a antibióticos de Acinetobacter baumannii en un hospital de Colombia

Objetivo: Identificar patrones de resistencia en los aislamientos de A. baumannii obtenidos en una unidad de cuidados intensivos de Cali, Colombia. Diseño: Estudio descriptivo, prospectivo de corte transversal. Institución: Clínica Universitaria Rafael Uribe Uribe, Cali, Colombia. Materiales: Los aislamientos se obtuvieron de cultivos de muestras de sangre, heridas quirúrgicas, secreción nasal, orina, secreción uretral y puntas de catéter. Intervenciones: Se recolectaron 52 aislamientos durante los años 2009 y 2010. Mediante el análisis del antibiograma se identificaron patrones de resistencia (antibiotipos), se realizó antibiograma cuantitativo y se construyó un cladograma basado en el agrupamiento por el método de promedios aritméticos de grupos apareados no ponderados (conocido en inglés como UPGMA). Principales medidas de resultados: Medida de la concentración mínima inhibitoria (CMI) y el coeficiente de similitud generado por las distancias de los diámetros de los halos de inhibición entre dos aislamientos (antibiograma cuantitativo). Resultados: Se identificaron 5 antibiotipos; el 50% de los aislamientos se agruparon en el antibiotipo 1, con resistencia a todos los antibióticos y sensibilidad a tigeciclina y sulperazona; el antibiotipo 4 agrupó los aislamientos con resistencia a todos los antibióticos (19,3%). En el antibiograma cuantitativo se identificó dos clados con 5 y 47 aislamientos, respectivamente. Conclusiones: Los aislamientos de Acinetobacter baumannii tuvieron pocas diferencias fenotípicas y es probable que presenten alguna de las β-lactamasas tipo OXA

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.info:eu-repo/semantics/publishedVersio

Search for High-energy Neutrinos from Binary Neutron Star Merger GW170817 with ANTARES, IceCube, and the Pierre Auger Observatory

The Advanced LIGO and Advanced Virgo observatories recently discovered gravitational waves from a binary neutron star inspiral. A short gamma-ray burst (GRB) that followed the merger of this binary was also recorded by the Fermi Gamma-ray Burst Monitor (Fermi-GBM), and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory (INTEGRAL), indicating particle acceleration by the source. The precise location of the event was determined by optical detections of emission following the merger. We searched for high-energy neutrinos from the merger in the GeV–EeV energy range using the Antares, IceCube, and Pierre Auger Observatories. No neutrinos directionally coincident with the source were detected within ±500 s around the merger time. Additionally, no MeV neutrino burst signal was detected coincident with the merger. We further carried out an extended search in the direction of the source for high-energy neutrinos within the 14 day period following the merger, but found no evidence of emission. We used these results to probe dissipation mechanisms in relativistic outflows driven by the binary neutron star merger. The non-detection is consistent with model predictions of short GRBs observed at a large off-axis angle