Eficacia terapéutica y seguridad del tocilizumab en COVID-19 / Therapeutic efficacy of tocilizumab in COVID-19

A la fecha, excepto los glucocorticoides, ningún otro tratamiento farmacológico ha demostrado disminución de la mortalidad en pacientes con COVID-19 grave-crítico. Con el objetivo de discutir su utilidad en la terapéutica, se realizó una revisión y lectura crítica de los estudios publicados más significativos sobre el uso de tocilizumab.Se llevó adelante una búsqueda en las principales bases de datos bibliográficas priorizando la inclusión de revisiones sistemáticas y ensayos clínicos aleatorizados controlados (ERC) que analizaran el efecto del tocilizumab en COVID-19 en diferentes puntos de valoración.Se incluyeron 5 ERC y 4 metaanálisis en la evaluación, todos ellos incluyeron pacientes con COVID-19 confirmado y mayoritariamente graves-críticos. El punto de valoración principal (PVP) fue la mortalidad a los 28 días y como resultado secundario de relevancia, la progresión a ventilación mecánica invasiva (VMI). Se analizó, además, la seguridad de la intervención, fundamentalmente a nivel de la ocurrencia de infecciones secundarias.Del análisis surge que la mayor posibilidad de beneficio parece estar circunscripta a pacientes con enfermedad grave-crítica, que reciben corticoides, con marcadores de inflamación elevados (PCR >10 mg/dL) y enfermedad rápidamente progresiva. Existe alto grado de certeza respecto del impacto del tocilizumab en evitar la progresión a VMI, con una pequeña magnitud del efecto y moderado grado de certeza respecto de su impacto en la mortalidad; además de que resultó una medicación segura

Up until now, other than corticosteroids, no other pharmacological treatment has shown a decrease in mortality rate in patients with severe-critical COVID-19. In order to discuss its place in therapy, a review and critical reading of the most significant published studies on the use of tocilizumab was carried out.Search was done in the main bibliographic databases, prioritizing the inclusion of systematic reviews and randomized controlled clinical trials (RCTs); that analyzed the effect of tocilizumab on COVID-19 at different endpoints.5 RCTs and 4 meta-analysis were considered in the evaluation, all of them including patients with confirmed COVID-19 and predominantly severe-critical illness. The primary endpoint was 28-day all-cause mortality and, as a secondary outcome of relevance, progression to invasive mechanical ventilation. The safety of the intervention was also analyzed, mainly the occurrence of secondary infections.From our analysis it appears that the greatest possibility of benefit seems to be limited to patients with severe-critical illness, who receive corticosteroids, with high markers of inflammation values (CRP> 10 mg/dL) and rapidly progressive disease. There is high certainty regarding the impact of tocilizumab in preventing progression to IMV, with a small effect size and moderate certainty regarding its impact on mortality. Moreover, it was a well-tolerated and safe medication

[Guidelines for management of community-acquired pneumonia in adults]. / Neumonía adquirida de la comunidad en adultos. Recomendaciones sobre su atención.

Community-acquired pneumonia in adults is a common cause of morbidity and mortality particularly in the elderly and in patients with comorbidities. Most episodes are of bacterial origin, Streptococcus pneumoniae is the most frequently isolated pathogen. Epidemiological surveillance provides information about changes in microorganisms and their susceptibility. In recent years there has been an increase in cases caused by community-acquired meticillin resistant Staphylococcus aureus and Legionella sp. The chest radiograph is essential as a diagnostic tool. CURB-65 score and pulse oximetry allow stratifying patients into those who require outpatient care, general hospital room or admission to intensive care unit. Diagnostic studies and empirical antimicrobial therapy are also based on this stratification. The use of biomarkers such as procalcitonin or C-reactive protein is not part of the initial evaluation because its use has not been shown to modify the initial approach. We recommend treatment with amoxicillin for outpatients under 65 year old and without comorbidities, for patients 65 years or more or with comorbidities amoxicillin-clavulanic/sulbactam, for patients hospitalized in general ward ampicillin-sulbactam with or without the addition of clarithromycin, and for patients admitted to intensive care unit ampicillin-sulbactam plus clarithromycin. Suggested treatment duration is 5 to 7 days for outpatients and 7 to 10 for those who are hospitalized. During the influenza season addition of oseltamivir for hospitalized patients and for those with comorbidities is suggested.

Neumonía adquirida de la comunidad en adultos: Recomendaciones sobre su atención / Guidelines for management of community-acquired pneumonia in adults

La neumonía adquirida en la comunidad (NAC) en adultos es causa frecuente de morbilidad y mortalidad, especialmente en adultos mayores y en sujetos con comorbilidades previas. La mayoría de los episodios son de etiología bacteriana, Streptococcus pneumoniae es el patógeno aislado con mayor frecuencia. La vigilancia epidemiológica permite conocer los cambios en los microorganismos productores y su sensibilidad a los antimicrobianos; recientemente se ha observado un incremento en aislamientos de Staphylococcus aureus resistente a la meticilina y Legionella sp. La radiografía de tórax resulta imprescindible como herramienta diagnóstica. El score CURB-65 y la oximetría de pulso permiten estratificar a los pacientes en aquellos que requieren manejo ambulatorio, hospitalización en sala general o unidad de terapia intensiva. Los estudios diagnósticos y el tratamiento antimicrobiano empírico también se basan en esta estratificación. Los biomarcadores tales como procalcitonina o proteína-C reactiva no son parte de la evaluación inicial dado que su utilización no demostró modificar el manejo de los episodios de NAC. El tratamiento antibiótico sugerido para pacientes ambulatorios menores de 65 años sin comorbilidades es amoxicilina; pacientes ≥ 65 años o con comorbilidades: amoxicilina-clavulánico/sulbactam; hospitalizados en sala general: ampicilina sulbactam con o sin claritromicina; pacientes admitidos a unidad de terapia intensiva: ampicilina-sulbactam más claritromicina. La duración del tratamiento es de 5 a 7 días para tratamiento ambulatorio y 7 a 10 para los hospitalizados. En época de circulación del virus de la influenza se sugiere el agregado de oseltamivir para los pacientes hospitalizados y para aquellos con comorbilidades.

Community-acquired pneumonia in adults is a common cause of morbidity and mortality particularly in the elderly and in patients with comorbidities. Most episodes are of bacterial origin, Streptococcus pneumoniae is the most frequently isolated pathogen. Epidemiological surveillance provides information about changes in microorganisms and their susceptibility. In recent years there has been an increase in cases caused by community-acquired meticillin resistant Staphylococcus aureus and Legionella sp. The chest radiograph is essential as a diagnostic tool. CURB-65 score and pulse oximetry allow stratifying patients into those who require outpatient care, general hospital room or admission to intensive care unit. Diagnostic studies and empirical antimicrobial therapy are also based on this stratification. The use of biomarkers such as procalcitonin or C-reactive protein is not part of the initial evaluation because its use has not been shown to modify the initial approach. We recommend treatment with amoxicillin for outpatients under 65 year old and without comorbidities, for patients 65 years or more or with comorbidities amoxicillin-clavulanic/sulbactam, for patients hospitalized in general ward ampicillin-sulbactam with or without the addition of clarithromycin, and for patients admitted to intensive care unit ampicillin-sulbactam plus clarithromycin. Suggested treatment duration is 5 to 7 days for outpatients and 7 to 10 for those who are hospitalized. During the influenza season addition of oseltamivir for hospitalized patients and for those with comorbidities is suggested.

Outbreak of a cluster with epidemic behavior due to Serratia marcescens after colistin administration in a hospital setting.

Serratia marcescens causes health care-associated infections with important morbidity and mortality. Particularly, outbreaks produced by multidrug-resistant isolates of this species, which is already naturally resistant to several antibiotics, including colistin, are usually described with high rates of fatal outcomes throughout the world. Thus, it is important to survey factors associated with increasing frequency and/or emergence of multidrug-resistant S. marcescens nosocomial infections. We report the investigation and control of an outbreak with 40% mortality due to multidrug-resistant S. marcescens infections that happened from November 2007 to April 2008 after treatment with colistin for Acinetobacter baumannii meningitis was started at hospital H1 in 2005. Since that year, the epidemiological pattern of frequently recovered species has changed, with an increase of S. marcescens and Proteus mirabilis infections in 2006 in concordance with a significant decrease of the numbers of P. aeruginosa and A. baumannii isolates. A single pulsed-field gel electrophoresis (PFGE) cluster of S. marcescens isolates was identified during the outbreak. When this cluster was compared with S. marcescens strains (n = 21) from 10 other hospitals (1997 to 2010), it was also identified in both sporadic and outbreak isolates circulating in 4 hospitals in Argentina. In132::ISCR1::blaCTX-M-2 was associated with the multidrug-resistant cluster with epidemic behavior when isolated from outbreaks. Standard infection control interventions interrupted transmission of this cluster even when treatment with colistin continued in several wards of hospital H1 until now. Optimizing use of colistin should be achieved simultaneously with improved infection control to prevent the emergence of species naturally resistant to colistin, such as S. marcescens and P. mirabilis.