RESUMO
Hypervirulent Klebsiella pneumoniae is known for its increased extracellular polysaccharide production. Biofilm matrices of hypervirulent K. pneumoniae have increased polysaccharide abundance and are uniquely susceptible to disruption by peptide bactenecin 7 (bac7 (1-35)). Here, using confocal microscopy, we show that polysaccharides within the biofilm matrix collapse following bac7 (1-35) treatment. This collapse led to the release of cells from the biofilm, which were then killed by the peptide. Characterization of truncated peptide analogs revealed that their interactions with polysaccharide were responsible for the biofilm matrix changes that accompany bac7 (1-35) treatment. Ultraviolet photodissociation mass spectrometry with the parental peptide or a truncated analog bac7 (10-35) reveal the important regions for bac7 (1-35) complexing with polysaccharides. Finally, we tested bac7 (1-35) using a murine skin abscess model and observed a significant decrease in the bacterial burden. These findings unveil the potential of bac7 (1-35) polysaccharide interactions to collapse K. pneumoniae biofilms.
RESUMO
OBJECTIVES: To describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) treated in hospital emergency departments (EDs) in Spain, and to assess associations between characteristics and outcomes. MATERIAL AND METHODS: Prospective, multicenter, nested-cohort study. Sixty-one EDs included a random sample of all patients diagnosed with COVID-19 between March 1 and April 30, 2020. Demographic and baseline health information, including concomitant conditions; clinical characteristics related to the ED visit and complementary test results; and treatments were recorded throughout the episode in the ED. We calculated crude and adjusted odds ratios for risk of in-hospital death and a composite outcome consisting of the following events: intensive care unit admission, orotracheal intubation or mechanical ventilation, or in-hospital death. The logistic regression models were constructed with 3 groups of independent variables: the demographic and baseline health characteristics, clinical characteristics and complementary test results related to the ED episode, and treatments. RESULTS: The mean (SD) age of patients was 62 (18) years. Most had high- or low-grade fever, dry cough, dyspnea, and diarrhea. The most common concomitant conditions were cardiovascular diseases, followed by respiratory diseases and cancer. Baseline patient characteristics that showed a direct and independent association with worse outcome (death and the composite outcome) were age and obesity. Clinical variables directly associated with worse outcomes were impaired consciousness and pulmonary crackles; headache was inversely associated with worse outcomes. Complementary test findings that were directly associated with outcomes were bilateral lung infiltrates, lymphopenia, a high platelet count, a D-dimer concentration over 500 mg/dL, and a lactate-dehydrogenase concentration over 250 IU/L in blood. CONCLUSION: This profile of the clinical characteristics and comorbidity of patients with COVID-19 treated in EDs helps us predict outcomes and identify cases at risk of exacerbation. The information can facilitate preventive measures and improve outcomes.
OBJETIVO: Describir las características clínicas de los pacientes con COVID-19 atendidos en los servicios de urgencias hospitalarios (SUH) españoles y evaluar su asociación con los resultados de su evolución. METODO: Estudio multicéntrico, anidado en una cohorte prospectiva. Participaron 61 SUH que incluyeron pacientes seleccionados aleatoriamente de todos los diagnosticados de COVID-19 entre el 1 de marzo y el 30 de abril de 2020. Se recogieron características basales, clínicas, de exploraciones complementarias y terapéuticas del episodio en los SUH. Se calcularon las odds ratio (OR) asociadas a la mortalidad intrahospitalaria y al evento combinado formado por el ingreso en unidad de cuidados intensivos (UCI), la intubación orotraqueal o ventilación mecánica invasiva (IOT/ VMI), crudas y ajustadas con modelos de regresión logística para tres grupos de variables independientes: basales, clínicas y de exploraciones complementarias. RESULTADOS: La edad media fue de 62 años (DE 18). La mayoría manifestaron fiebre, tos seca, disnea, febrícula y diarrea. Las comorbilidades más frecuentes fueron las enfermedades cardiovasculares, seguidas de las respiratorias y el cáncer. Las variables basales que se asociaron independientemente y de forma directa a peores resultados evolutivos (tanto a mortalidad como a evento combinado) fueron edad y obesidad; las variables clínicas fueron disminución de consciencia y crepitantes a la auscultación pulmonar, y de forma inversa cefalea; y las variables de resultados de exploraciones complementarias fueron infiltrados pulmonares bilaterales y cardiomegalia radiológicos, y linfopenia, hiperplaquetosis, dímero-D > 500 mg/dL y lactato-deshidrogenasa > 250 UI/L en la analítica. CONCLUSIONES: Conocer las características clínicas y la comorbilidad de los pacientes con COVID-19 atendidos en urgencias permite identificar precozmente a la población más susceptible de empeorar, para prever y mejorar los resultados.