Discovery of Novel Substituted N-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors.

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds 6, 15, 29, 40, 43, 46, 47, and 54 exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV. The preliminary mechanistic studies indicated that compounds 6 and 43 possibly target the HAdV DNA replication process, while compounds 46 and 47 suppress later steps of HAdV life cycle. Notably, among these derivatives, compound 15 showed improved anti-HAdV activity (IC50 = 0.27 µM), significantly decreased cytotoxicity (CC50 = 156.8 µM), and low in vivo toxicity (maximum tolerated dose = 150 mg/kg in hamster) as compared with niclosamide, supporting its further in vivo efficacy studies for the treatment of HAdV infections.

Outpatient Parenteral Antimicrobial Treatment for Non-Cystic Fibrosis Bronchiectasis Exacerbations: A Prospective Multicentre Observational Cohort Study.

BACKGROUND: The recently published guidelines of the Spanish Society of Pulmonology and Thoracic Surgery encourage physicians to use outpatient antimicrobial therapy to treat exacerbations in patients with non-cystic fibrosis bronchiectasis (NCFB). The published literature on this topic, however, is scarce. METHODS: We report a prospective observational cohort study of patients with NCFB who received treatment at home for at least one exacerbation episode between September 2012 and September 2017 as part of an outpatient parenteral antimicrobial therapy (OPAT) program. Patients were included in the analysis if they fulfilled all of the following criteria: established diagnosis of bronchiectasis according to current guidelines criteria, clinical exacerbation, requiring intravenous antibiotics because of failure to respond to oral antibiotics, or isolation of a microorganism resistant to oral options. OBJECTIVES: To evaluate the effectiveness and safety of the treatment of patients with NCFB exacerbations in an OPAT program under "real-world" conditions. RESULTS: Sixty-seven patients were treated in the OPAT program due to bacterial exacerbations of NCFB. Forty-five (67.2%) patients were admitted to hospital for a median of 7 days before starting OPAT. Sixty-three (94%) patients achieved resolution of the exacerbation at the end of therapy. Four patients needed hospital readmission, and one died. The OPAT program saved 11,586 days of hospital admission, equivalent to EUR 7,866,904. CONCLUSIONS: OPAT appears to be a safe, effective, and efficient strategy for treating patients with exacerbations of NCFB.

Urinary tract infection in kidney transplant recipients / Infección del Tracto Urinario en el Paciente Trasplantado Renal

Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients with a reported incidence from 25% to 75%, varies widely likely due to differences in definition, diagnostic criteria, study design, and length of observation. We sought reviews the incidence and importance of urinary tract infection on graft survival, the microbiology with special emphasis on multidrug resistant microorganisms, the therapeutic management of UTI and the prophylaxis of recurrent UTI among solid organ transplant recipients, highlighting the need for prospective clinical trials to unify the clinical management in this population

Las complicaciones infecciosas siguen siendo una causa importante de morbimortalidad entre los pacientes trasplantados de órgano sólido. La infección del tracto urinario (ITU) es la complicación infecciosa más frecuente en los trasplantados renales con una incidencia que varía entre el 25 y el 75% según los estudios, debido a diferencias en la definición, criterios diagnósticos, diseño de los estudios y tiempo de seguimiento. Revisamos la incidencia e importancia de la ITU en la supervivencia del injerto, la microbiología, con especial énfasis en los microorganismos multirresistentes, el manejo terapéutico de la ITU y la profilaxis de la infección urinaria recurrente en los receptores de trasplante renal destacando la necesidad de ensayos clínicos prospectivos que unifiquen el manejo clínico en esta población

Urinary tract infection in kidney transplant recipients.

Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients with a reported incidence from 25% to 75%, varies widely likely due to differences in definition, diagnostic criteria, study design, and length of observation. We sought reviews the incidence and importance of urinary tract infection on graft survival, the microbiology with special emphasis on multidrug resistant microorganisms, the therapeutic management of UTI and the prophylaxis of recurrent UTI among solid organ transplant recipients, highlighting the need for prospective clinical trials to unify the clinical management in this population.

Acinetobacter baumannii in critically ill patients: Molecular epidemiology, clinical features and predictors of mortality / Acinetobacter baumannii en pacientes críticos: epidemiología molecular, características clínicas y predictores de mortalidad

INTRODUCTION: The main aim of this study was to assess changes in the epidemiology and clinical presentation of Acinetobacter baumannii over a 10-year period, as well as risk factors of mortality in infected patients. METHOD: Prospective, multicentre, hospital-based cohort studies including critically ill patients with A. baumannii isolated from any clinical sample were included. These were divided into a first period ('2000 study') (one month), and a second period ('2010 study') (two months). Molecular typing was performed by REP-PCR, PFGE and MSLT. The primary endpoint was 30-day mortality. RESULTS: In 2000 and 2010, 103 and 108 patients were included, and the incidence of A. baumanniicolonization/infection in the ICU decreased in 2010 (1.23 vs. 4.35 cases/1000 patient-days; p < 0.0001). No differences were found in the colonization rates (44.3 vs. 38.6%) or infected patients (55.7 vs. 61.4%) in both periods. Overall, 30-day mortality was similar in both periods (29.1 vs. 27.8%). The rate of pneumonia increased from 46.2 in 2000 to 64.8% in 2010 (p < 0.001). Performing MSLT, 18 different sequence types (ST) were identified (18 in 2000, 8 in 2010), but ST2 and ST79 were the predominant clones. ST2 isolates in the ICU increased from 53.4% in the year 2000 to 73.8% in 2010 (p = 0.002). In patients with A. baumanniiinfection, the multivariate analysis identified appropriate antimicrobial therapy and ST79 clonal group as protective factors for mortality. CONCLUSIONS: At 10 years of the first analysis, some variations have been observed in the epidemiology of A. baumannii in the ICU, with no changes in mortality. Epidemic ST79 clone seems to be associated with a better prognosis and adequate treatment is crucial in terms of survival

INTRODUCCIÓN: El principal objetivo fue evaluar los cambios en la epidemiología a lo largo de un periodo de 10años, así como la presentación clínica y los factores predictores de mortalidad en los pacientes críticos infectados por Acinetobacter baumannii. MÉTODO: Estudio de cohortes prospectivo y multicéntrico en el que se incluyeron pacientes críticos con A. baumannii aislado de cualquier muestra clínica. Se consideró un primer período («estudio de 2000») (un mes) y un segundo («estudio de 2010») (2 meses). La tipificación molecular se realizó mediante REP-PCR, PFGE y MSLT. La variable resultado primaria fue la mortalidad a los 30días. RESULTADOS: En 2000 y 2010 se incluyeron 103 y 108 pacientes, respectivamente, y la incidencia de colonización/infección por A. baumannii en la UCI disminuyó en 2010 respecto al 2000 (1,23 vs. 4,35 casos/1.000 pacientes-días; p < 0,0001). No se encontraron diferencias en la tasa de colonización (44,3 vs. 38,6%) o infección (55,7 vs. 61,4%) en ambos periodos. En general, la mortalidad a los30 días fue similar en ambos periodos (29,1 vs. 27,8%). La tasa de neumonía aumentó desde el 46,2% en 2000 al 64,8% en 2010 (p < 0,001). Mediante MSLT, se identificaron 18 tipos de secuencias diferentes (ST) (18 en 2000, 8 en 2010), pero ST2 y ST79 fueron los clones predominantes. La identificación de ST2 aumentó en la UCI desde el 53,4% en 2000 al 73,8% en 2010 (p = 0,002). En los pacientes infectados, el tratamiento antimicrobiano apropiado y el grupo clonal ST79 fueron factores protectores de mortalidad en el análisis multivariante. CONCLUSIONES: A los 10 años del primer análisis se han observado algunos cambios en la epidemiología de A. baumannii en la UCI, sin cambios en la mortalidad. El clon ST79 epidémico parece estar asociado con un mejor pronóstico, y el tratamiento adecuado es crucial en términos de supervivencia

Acinetobacter baumannii in critically ill patients: Molecular epidemiology, clinical features and predictors of mortality.

INTRODUCTION: The main aim of this study was to assess changes in the epidemiology and clinical presentation of Acinetobacter baumannii over a 10-year period, as well as risk factors of mortality in infected patients. METHOD: Prospective, multicentre, hospital-based cohort studies including critically ill patients with A. baumannii isolated from any clinical sample were included. These were divided into a first period ("2000 study") (one month), and a second period ("2010 study") (two months). Molecular typing was performed by REP-PCR, PFGE and MSLT. The primary endpoint was 30-day mortality. RESULTS: In 2000 and 2010, 103 and 108 patients were included, and the incidence of A. baumannii colonization/infection in the ICU decreased in 2010 (1.23 vs. 4.35 cases/1000 patient-days; p<0.0001). No differences were found in the colonization rates (44.3 vs. 38.6%) or infected patients (55.7 vs. 61.4%) in both periods. Overall, 30-day mortality was similar in both periods (29.1 vs. 27.8%). The rate of pneumonia increased from 46.2 in 2000 to 64.8% in 2010 (p<0.001). Performing MSLT, 18 different sequence types (ST) were identified (18 in 2000, 8 in 2010), but ST2 and ST79 were the predominant clones. ST2 isolates in the ICU increased from 53.4% in the year 2000 to 73.8% in 2010 (p=0.002). In patients with A. baumannii infection, the multivariate analysis identified appropriate antimicrobial therapy and ST79 clonal group as protective factors for mortality. CONCLUSIONS: At 10 years of the first analysis, some variations have been observed in the epidemiology of A. baumannii in the ICU, with no changes in mortality. Epidemic ST79 clone seems to be associated with a better prognosis and adequate treatment is crucial in terms of survival.

La interconsulta de enfermedades infecciosas es una actividad clave para los servicios y unidades de enfermedades infecciosas y para el hospital / The referral of infectious diseases is a key activity for infectious diseases departments and units, as well as for the hospital

La interconsulta de enfermedades infecciosas (ICEI) es una actividad nuclear de los servicios y unidades de enfermedades infecciosas y es, sin duda, la que tiene mayor impacto potencial en el hospital por su carácter transversal, y por la aparición de las resistencias bacterianas y la crisis de los antimicrobianos. Sin embargo, no hay un modelo estándar de interconsulta, no existe formación reglada, y la evaluación de las ICEI se limita a la descripción cuantitativa. Paradójicamente, las ICEI están en riesgo en un sistema sanitario que exige más calidad y eficiencia. El objetivo de esta revisión es analizar los conocimientos disponibles sobre las ICEI, la definición, las características principales, los objetivos, el método y la evaluación de los resultados, y proponer mejoras para esta actividad clave de los servicios y unidades de enfermedades infecciosas y del hospital

Infectious diseases referrals (IDR) is a core activity of infectious diseases departments, and is certainly the one with the greatest potential impact on the hospital due to their cross-sectional nature, and with the emergence of a bacterial resistance and antimicrobial crisis. However, there is no standard model for IDR, no official training, and evaluation is merely descriptive. Paradoxically IDR are at risk in a health system that demands more quality and efficiency. The aim of this review is to assess what is known about IDR, its definition, key features, objectives, method, and the evaluation of results, and to suggest improvements to this key activity for the infectious diseases departments and the hospital

[The referral of infectious diseases is a key activity for infectious diseases departments and units, as well as for the hospital]. / La interconsulta de enfermedades infecciosas es una actividad clave para los servicios y unidades de enfermedades infecciosas y para el hospital.

Infectious diseases referrals (IDR) is a core activity of infectious diseases departments, and is certainly the one with the greatest potential impact on the hospital due to their cross-sectional nature, and with the emergence of a bacterial resistance and antimicrobial crisis. However, there is no standard model for IDR, no official training, and evaluation is merely descriptive. Paradoxically IDR are at risk in a health system that demands more quality and efficiency. The aim of this review is to assess what is known about IDR, its definition, key features, objectives, method, and the evaluation of results, and to suggest improvements to this key activity for the infectious diseases departments and the hospital.

[Infection by the pandemic virus (H1N1) 2009 in Andalusia]. / Infección por virus pandémico (H1N1) 2009 en Andalucía.

In April 2009, in response to the WHO's alert due to the existence of human infection cases with a new AH1N1 influenza virus, known as swine flu, Andalusian Health Authorities trigger an specific action plan. The surveillance actions developped provided us with appropriate clinical, epidemiological and virological characteristics of the disease. During the first few days, contingency plans were set up based on epidemiological surveillance and outbreak control measures were adopted through early alert and rapid response systems. After phase 6 was declared, influenza sentinel and severe cases surveillance were used in order to plan healthcare services, to reduce transmission and to identify and protect the most vulnerable population groups. Behaviour of pandemic influenza in Andalusia was similar to that observed in the rest of the world. Atack rate was similar to a seasonal flu and the peak was reached at the 46th/2009 week. Most of them were mild cases and affected particularly to young people. The average age of hospitalised patients was 32. Prior pulmonary disease, smoking and morbid obesity (BMI > 40) were the most common pathologies and risk factors in severe cases. An impact scenario of pandemic wave in Andalusia, with an expected attack rate from 2 to 5%, was prepared considering watt observed in the southern hemisphere. Characteristics of the epidemic concerning its extent, severity and mortality rate were adjusted to this scenario.

Hemocultivos en el servicio de urgencias / Blood cultures in the emergency department

INTRODUCCIÓN. La realización de hemocultivos en el servicio de urgencias es una práctica común pero discutida porque, comparada con otros análisis de urgencias, requieren el doble de tiempo para la extracción y una técnica depurada para evitar contaminaciones, y carecen de utilidad diagnóstica inmediata. MÉTODOS. Estudio prospectivo de todos los pacientes adultos con hemocultivos positivos realizados en el servicio de urgencias y análisis de la rentabilidad, la calidad, la incidencia, la etiología, la clínica y el pronóstico de estas bacteriemias. RESULTADOS. Durante el período de estudio se indicaron 5,2 hemocultivos por cada 1.000 pacientes atendidos en urgencias. La rentabilidad diagnóstica (n.º de bacteriemias/n.º de hemocultivos realizados) fue del 20% y la tasa de contaminación (n.º de contaminantes/n.º de hemocultivos realizados) fue del 1%. La incidencia de bacteriemia fue de 0,99 episodios por cada 1.000 pacientes atendidos en el servicio de urgencias y de 10,3 episodios por cada 1.000 ingresos. La etiología predominante fueron las bacterias gramnegativas (57%). La sepsis fue la manifestación clínica más frecuente (50%), seguida de la sepsis grave (40%) y del shock séptico (10%).La mortalidad fue del 22%. La diabetes mellitus y la sepsis grave/shock séptico fueron los factores independientes asociados con la mortalidad. CONCLUSIONES. La rentabilidad y la calidad de los hemocultivos en el servicio de urgencias es elevada. Las bacterias gramnegativas son la etiología predominante. La presentación clínica de los pacientes con bacteriemia es grave y los factores independientes de mal pronóstico son la diabetes mellitus y la sepsis grave y/o el shock séptico (AU)

INTRODUCTION. Culture of emergency room blood samples is common practice, but open to controversy. As compared to other emergency tests, blood collection requires twice as much time and needs a refined technique to avoid contamination, and the study has no immediate diagnostic utility. METHODS. This prospective study includes consecutive adult patients with positive emergency room blood cultures. We analyzed the diagnostic sensitivity and contamination rate of the cultures and the etiology, clinical features and prognosis of the bacteremias encountered. RESULTS. During the study period, 5.2 blood cultures were indicated per 1000 patients attended in the emergency room. The diagnostic yield (positive blood cultures/total cultures) was 20% and the contamination rate(contaminated blood cultures/total cultures) was 1%.The incidence of bacteriemia was 0.99 episodes per 1000 patients attended in the emergency room and 10.3 episode per 1000 hospitalized patients. Gram-negative bacteria predominated (57%). Sepsis was the most frequent clinical manifestation (50%), followed by severe sepsis (40%) and septic shock (10%). Mortality was 22%. Diabetes mellitus and severe sepsis/septic shockwere independent factors associated with mortality. CONCLUSIONS. Diagnostic performance and quality of emergency room blood cultures was high. The predominant etiology was gram-negative bacteria. Patients had a severe clinical presentation. Diabetes mellitus and severe sepsis and/or septic shock were independent prognostic factors of mortality (AU)

¿Tratamiento empírico de la fiebre de duración intermedia con doxiciclina? Réplica / Empirical treatment with doxycycline for fever of intermediate duration?. Reply

No disponible

La infección por el VIH : guía práctica

Guía cuyo objetivo es ser una herramienta útil para cualquier médico que necesite realizar una consulta sobre cualquier problema clínico relacionado con la infección por el VIH/SIDA. Además de la revisión y puesta al día de todos los capítulos de la edición anterior, se han incluido otros nuevos, como los dedicados a los efectos adversos del tratamiento antirretrovírico y al manejo de la coinfección por VIH/VHC.