Design, synthesis, biological evaluation and molecular dynamics of some novel 3-phenylpyrazolo[1,5-a]pyrimidine-2,7(1H,4H)-dione based compounds as anti-tubercular agents.

Decaprenylphosphoryl-ß-d-ribose-2'-epimerase (DprE1) is a druggable target which is being exploited for the development of new anti-TB agents. In the present work, we report developing a pharmacophore model and performing virtual screening of Asinex database using the developed pharmacophore model to get eight hits as potential DprE1 inhibitors. The hits were used as leads to design new 3-phenylpyrazolo[1,5-a]pyrimidine-2,7(1H,4H)-dione based potential anti-TB agents. On the basis of the identified lead molecules, a total of 18 compounds were synthesized and evaluated for their anti-TB activity by using MABA. ADMET predictions for all the compounds revealed that these compounds have drug-like and lead-like properties. One of the final compounds was found to exhibit potent anti-TB activity against Mycobacterium bovis.Communicated by Ramaswamy H. Sarma.

Modelo 5MPB-Toledo para predecir bacteriemia en los pacientes atendidos por infección en el servicio de urgencias / Predicting bacteremia in patients attended for infections in an emergency department: the 5MPB-Toledo model

Objetivo: Diseñar un modelo sencillo de riesgo para predecir bacteriemia en los pacientes atendidos por un episodio de infección en el servicio de urgencias hospitalario (SUH). Métodos: Estudio observacional, de cohortes retrospectivo, de todos los hemocultivos (SUH) extraídos en un SU en los pacientes adultos ($18 años) atendidos por infección desde el 1 de julio de 2018 hasta el 31 de marzo de 2019. Se analizaron 38 variables independientes (demográficas, comorbilidad, funcionales, clínicas y analíticas) que pudieran predecir la existencia de bacteriemia. Se realizó un estudio univariado y multivariable, mediante regresión logística, y después se construyó una escala de puntuación de riesgo. Resultados: Se incluyeron 2.181 episodios de HC extraídos. De ellos se consideraron como bacteriemias verdaderas 262 (12%) y como HC negativos 1.919 (88%). Entre los negativos, 1.755 (80,5%) no tuvieron crecimiento y 164 (7,5%) se consideraron contaminados. Se definió un modelo predictivo de bacteriemia con 5 variables (5MPB-Toledo). El modelo incluyó la temperatura > 38,3°C (1 punto), un índice de Charlson $ 3 (1 punto), la frecuencia respiratoria $ 22 respiraciones por minuto (1 punto), leucocitos > 12.000/mm3 (1 punto) y procalcitonina $ 0,51 ng/ml (4 puntos). Se categorizó a los pacientes en bajo (0-2 puntos), moderado (3-5 puntos) y alto (6-8 puntos) riesgo, con una probabilidad de bacteriemia de 1,1%, 10,5% y 77%, respectivamente. El ABC-COR del modelo tras remuestreo fue de 0,946 (IC 95%: 0,922-0,969). Conclusiones: El Modelo 5MPB-Toledo podría ser de utilidad para predecir bacteriemia en los pacientes atendidos por un episodio de infección en el SUH

Objectives: To develop a simple risk score to predict bacteremia in patients in our hospital emergency department for infection. Methods: Retrospective observational short study of all blood cultures ordered in the emergency department for adults (aged 18 or older) from July 1, 2018, to March 31, 2019. We gathered data on 38 independent variables (demographic, comorbidity, functional status, and laboratory findings) that might predict bacteremia. Univariate and multiple logistic regression analyses were applied to the data and a risk scale was developed. Results: A total of 2181 blood samples were cultured. True cases of bacteremia were confirmed in 262 (12%). The remaining 1919 cultures (88%) were negative. No growth was observed in 1755 (80.5%) of the negative cultures, and 164 (7.5%) were judged to be contaminated. The 5MPB-Toledo model identified 5 predictors of bacteremia: temperature higher than 38.3°C (1 point), a Charlson comorbidity index of 3 or more (1 point), respiratory frequency of at least 22 breaths/min (1 point), leukocyte count greater than 12 000/mm3 (1 point), and procalcitonin concentration of 0.51 ng/mL or higher (4 points). Low risk for bacteremia was indicated by a score of 0 to 2 points, intermediate risk by 3 to 5 points, and high risk by 6 to 8 points. Bacteremia in these 3 risk groups was predicted for 1.1%, 10.5%, and 77%, respectively. The model's area under the receiver operating characteristic curve was 0.946 (95% CI, 0.922-0.969). Conclusion: The 5MPB-Toledo score could be useful for predicting bacteremia in patients attended in hospital emergency departments for infection

Predicting bacteremia in patients attended for infections in an emergency department: the 5MPB-Toledo model. / Modelo 5MPB-Toledo para predecir bacteriemia en los pacientes atendidos por infección en el servicio de urgencias.

OBJECTIVES: To develop a simple risk score to predict bacteremia in patients in our hospital emergency department for infection. MATERIAL AND METHODS: Retrospective observational cohort study of all blood cultures ordered in the emergency department for adults (aged 18 or older) from July 1, 2018, to March 31, 2019. We gathered data on 38 independent variables (demographic, comorbidity, functional status, and laboratory findings) that might predict bacteremia. Univariate and multiple logistic regression analyses were applied to the data and a risk scale was developed. RESULTS: A total of 2181 blood samples were cultured. True cases of bacteremia were confirmed in 262 (12%). The remaining 1919 cultures (88%) were negative. No growth was observed in 1755 (80.5%) of the negative cultures, and 164 (7.5%) were judged to be contaminated. The 5MPB-Toledo model identified 5 predictors of bacteremia: temperature higher than 38.3°C (1 point), a Charlson comorbidity index of 3 or more (1 point), respiratory frequency of at least 22 breaths/min (1 point), leukocyte count greater than 12 000/mm3 (1 point), and procalcitonin concentration of 0.51 ng/mL or higher (4 points). Low risk for bacteremia was indicated by a score of 0 to 2 points, intermediate risk by 3 to 5 points, and high risk by 6 to 8 points. Bacteremia in these 3 risk groups was predicted for 1.1%, 10.5%, and 77%, respectively. The model's area under the receiver operating characteristic curve was 0.946 (95% CI, 0.922-0.969). CONCLUSION: The 5MPB-Toledo score could be useful for predicting bacteremia in patients attended in hospital emergency departments for infection.

OBJETIVO: Diseñar un modelo sencillo de riesgo para predecir bacteriemia en los pacientes atendidos por un episodio de infección en el servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, de cohortes retrospectivo, de todos los hemocultivos (HC) extraídos en un SUH en los pacientes adultos ($ 18 años) atendidos por infección desde el 1 de julio de 2018 hasta el 31 de marzo de 2019. Se analizaron 38 variables independientes (demográficas, comorbilidad, funcionales, clínicas y analíticas) que pudieran predecir la existencia de bacteriemia. Se realizó un estudio univariado y multivariable, mediante regresión logística, y después se construyó una escala de puntuación de riesgo. RESULTADOS: Se incluyeron 2.181 episodios de HC extraídos. De ellos se consideraron como bacteriemias verdaderas 262 (12%) y como HC negativos 1.919 (88%). Entre los negativos, 1.755 (80,5%) no tuvieron crecimiento y 164 (7,5%) se consideraron contaminados. Se definió un modelo predictivo de bacteriemia con 5 variables (5MPBToledo). El modelo incluyó la temperatura > 38,3°C (1 punto), un índice de Charlson $ 3 (1 punto), la frecuencia respiratoria $ 22 respiraciones por minuto (1 punto), leucocitos > 12.000/mm3 (1 punto) y procalcitonina $ 0,51 ng/ ml (4 puntos). Se categorizó a los pacientes en bajo (0-2 puntos), moderado (3-5 puntos) y alto (6-8 puntos) riesgo, con una probabilidad de bacteriemia de 1,1%, 10,5% y 77%, respectivamente. El ABC-COR del modelo tras remuestreo fue de 0,946 (IC 95%: 0,922-0,969). CONCLUSIONES: El Modelo 5MPB-Toledo podría ser de utilidad para predecir bacteriemia en los pacientes atendidos por un episodio de infección en los SUH.

Factores predictores de bacteriemia en los pacientes atendidos en el Servicio de Urgencias por infección / Predictive factors of bacteraemia in the patients seen in emergency departments due to infections

OBJETIVOS: Analizar los factores predictivos de bacteriemia en los pacientes atendidos en el servicio de urgencias (SU) por un episodio de infección. PACIENTES Y MÉTODOS: Estudio observacional, retrospectivo, descriptivo y analítico de todos los hemocultivos extraídos en un SU en los pacientes adultos (≥ 18 años) atendidos por infección desde el 1-1-2018 hasta el 1-7-2018. Se realizó seguimiento durante 30 días. Se analizaron 38 variables independientes (epidemiológicas, de comorbilidad, funcionales, clínicas y analíticas) que pudieran predecir la existencia de bacteriemia. Se realizó un estudio univariado y multivariante mediante regresión logística. RESULTADOS: Se incluyeron 1.425 episodios de hemocultivos extraídos. De ellos se consideraron como bacteriemias verdaderas 179 (12,6 %) y como HC negativos 1.246 (87,4 %). Entre los negativos, 1.130 (79,3%) no tuvieron crecimiento y 116 (8,1%) se consideraron contaminados. Cinco variables se asociaron de forma significativa como predictoras de bacteriemia verdadera: procalcitonina (PCT) sérica ≥ 0,51 ng/ml [odds ratio (OR): 4,52; intervalo de confianza (IC) al 95%: 4,20-4,84; p <0,001], temperatura > 38,3°C [OR: 1,60; IC al 95%: 1,29-1,90; p <0,001], presión arterial sistólica (PAS) < 100 mmHg [OR: 3,68; IC al 95%: 2,78-4,58; p <0,001], shock séptico [OR: 2,96; IC al 95%: 1,78-4,13; p <0,001] y la existencia de neoplasia [OR: 1,73; IC al 95%: 1,27-2,20; p <0,001]. CONCLUSIONES: Existen varios factores disponibles tras una primera valoración en el SU, entre ellos la PCT sérica, la temperatura, la hipotensión con/sin criterios de shock séptico y la existencia de neoplasia, que predicen la existencia de bacteriemia verdadera

OBJECTIVES: The aim of the study was to analyze predictive factors of bacteraemia in patients seen in the emergency department (ED) for an episode of infectious disease. PATIENTS AND METHODS: Observational, retrospective and descriptive analytical study of all blood cultures extracted in an ED in adult patients (≥ 18 years) seen in ED due to infectious disease from 1-1-2019 to 1-7-2019. The follow-up was carried out during 30 days. Thirty-eight variables for predicting bacteraemia were assessed. They covered epidemiological, comorbidity, functional, clinical and analytical factors. Univariate and multivariate logistic regression analysis was performed. RESULTS: A total of 1,425 blood cultures were finally enrolled in the study. Of those were considered true bacteremia 179 (12.6 %) and as negative blood cultures 1,246 (87.4 %). Amongst negatives, 1,130 (79.3%) without growth and 116 (8.1%) as contaminants blood cultures. Five variables were significantly associated with true bacteraemia: serum procalcitonin (PCT) ≥ 0.51 ng/ml [odds ratio (OR): 4.52; 95% confidence interval (CI): 4.20-4.84, P <.001], temperature > 38.3°C [OR:1.60; 95% CI:1.29-1.90, P <.001], systolic blood pressure (SBP) < 100 mmHg [OR:3.68; 95% CI:2.78-4.58, P <.001], septic shock [OR:2.96; 95% CI:1.78-4.13, P <.001] and malignancy [OR:1.73; 95% CI:1.27-2.20, P <.001]. CONCLUSIONS: Several factors evaluated in an initial assessment in the ED, including serum PCT, temperature, hypotension (with/without septic shock) and being malignancy, were found to predict true bacteraemia

Capacidad de la procalcitonina para diferenciar bacteriemia verdadera de los hemocultivos contaminados en el servicio de urgencias / Ability of procalcitonin to differentiate true bacteraemia from contaminated blood cultures in an emergency department

OBJETIVOS: Analizar y comparar la capacidad de la procalcitonina (PCT), proteína C reactiva (PCR) y leucocitos para diferenciar la bacteriemia verdadera de los hemocultivos (HC) contaminados en los pacientes atendidos en el servicio de urgencias (SU) por un episodio de infección. MÉTODOS: Estudio observacional, retrospectivo y analítico de todos los HC con crecimiento positivo extraídos en un SU en los pacientes adultos (≥ 18 años) durante los años 2016 y 2017. Se realizó seguimiento durante 30 días y se calculó el poder y rendimiento pronóstico de bacteriemia verdadera. RESULTADOS: Se incluyeron 266 casos de HC con crecimiento positivo. De ellos se consideraron como bacteriemias verdaderas 154 (57,9%) y como HC contaminantes 112 (42,1%). Para la predicción de bacteriemia verdadera la PCT obtiene un área bajo la curva Receiver Operating Characteristic (ABC-ROC) de 0,983 (IC 95%: 0,972-0,994; p < 0,001) y con un punto de corte de PCT ≥ 0,43 ng/ml se consigue una sensibilidad del 94%, una especificidad del 91%, un valor predictivo positivo de 94% y un valor predictivo negativo de 92%. El ABC-ROC obtenida para la PCR fue de 0,639 (IC 95%: 0,572-0,707; p < 0,001), para el recuento de leucocitos de 0,693 (IC 95%: 0,630-0,756; p < 0,001) y para las formas inmaduras (> 10% cayados) de 0,614 (IC 95%: 0,547-0,682; p = 0,001). Los valores medios al comparar la PCT en las bacteriemias verdaderas y los HC contaminados fueron de 3,44 ng/ml (DE 6,30) frente a 0,16ng/ml (DE 0,18), p < 0,001. CONCLUSIONES: En los HC con crecimiento positivo extraídos en el SU la PCT consigue el mejor rendimiento pronóstico de bacteriemia verdadera diferenciándola de los HC contaminados, mayor que la PCR y los leucocitos

OBJECTIVES: To analyse and compare the ability of procalcitonin (PCT), C-reactive protein (CRP) and leukocytes to differentiate true bacteraemia from contaminated blood cultures in patients seen in the emergency department (ED) for an episode of infectious disease. METHODS: Observational, retrospective and descriptive analytical study of all blood cultures with positive growth extracted in an ED in adult patients (≥ 18 years) during 2016 and 2017. The follow-up was carried out over a 30-day period to calculate the predictive power and the prognostic performance for true bacteraemia. RESULTS: A total of 266 blood cultures with positive growth were included in the study. Out of these, 154 (57.9%) were considered true bacteraemia and 112 (42.1%) were considered to be contaminated blood cultures. The area under the Receiver Operating Characteristic curve (AUC-ROC) for PCT to predict true bacteraemia was 0.983 (95% CI: 0.972-0.994; P < 0.001) and, considering a cut-off value of ≥ 0.43 ng/ml, PCT achieved 94% sensitivity, 91% specificity, positive predictive value of 94%, and negative predictive value of 92%. The AUC-ROC obtained for CRP was 0.639 (95% CI: 0.572-0.707, P < .001), for leukocytes of 0.693 (95% CI: 0.630-0.756, P < .001) and for immature leukocytes (> 10% bands) of 0.614 (95% CI: 0.547-0.682, P < .001). The mean values for PCT were 3.44 (SD 6.30) ng/ml in true bacteraemia vs. 0.16 (SD 0.18) ng/ml in contaminated blood cultures (P < .001). CONCLUSIONS: In blood cultures with positive growth extracted in an ED, PCT achieves the best prognostic performance of true bacteraemia vs. contaminated blood cultures, better than CRP and leukocytes

Biomarcadores: otra herramienta de ayuda para predecir bacteriemia en el servicio de urgencias / Biomarkers: Another help tool to predict bacteriemia in the emergency department

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Ability of procalcitonin to differentiate true bacteraemia from contaminated blood cultures in an emergency department. / Capacidad de la procalcitonina para diferenciar bacteriemia verdadera de los hemocultivos contaminados en el servicio de urgencias.

OBJECTIVES: To analyse and compare the ability of procalcitonin (PCT), C-reactive protein (CRP) and leukocytes to differentiate true bacteraemia from contaminated blood cultures in patients seen in the emergency department (ED) for an episode of infectious disease. METHODS: Observational, retrospective and descriptive analytical study of all blood cultures with positive growth extracted in an ED in adult patients (≥18 years) during 2016 and 2017. The follow-up was carried out over a 30-day period to calculate the predictive power and the prognostic performance for true bacteraemia. RESULTS: A total of 266 blood cultures with positive growth were included in the study. Out of these, 154 (57.9%) were considered true bacteraemia and 112 (42.1%) were considered to be contaminated blood cultures. The area under the Receiver Operating Characteristic curve (AUC-ROC) for PCT to predict true bacteraemia was 0.983 (95% CI: 0.972-0.994; P<0.001) and, considering a cut-off value of≥0.43 ng/ml, PCT achieved 94% sensitivity, 91% specificity, positive predictive value of 94%, and negative predictive value of 92%. The AUC-ROC obtained for CRP was 0.639 (95% CI: 0.572-0.707, P<.001), for leukocytes of 0.693 (95% CI: 0.630-0.756, P<.001) and for immature leukocytes (>10% bands) of 0.614 (95% CI: 0.547-0.682, P<.001). The mean values for PCT were 3.44 (SD 6.30) ng/ml in true bacteraemia vs. 0.16 (SD 0.18) ng/ml in contaminated blood cultures (P<.001). CONCLUSIONS: In blood cultures with positive growth extracted in an ED, PCT achieves the best prognostic performance of true bacteraemia vs. contaminated blood cultures, better than CRP and leukocytes.

Rendimiento pronóstico de mortalidad a corto plazo del fragmento N-terminal del propéptido natriurético cerebral en ancianos con infección en el servicio de urgencias / Usefulness of the N-terminal pro brain natriuretic peptide as short-term prognostic factor for mortality in the elderly patients with infection seen in emergency departments

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Consideraciones sobre la epidemiología de la sepsis grave adquirida en la comunidad / Considerations on the epidemiology of community-acquired severe sepsis

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