The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0–171.2] to 180.0 [135.4–227.9] mmHg and the ventilatory ratio from 1.73 [1.33–2.25] to 1.96 [1.61–2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01–1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01–1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93–1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.Instituto de Salud Carlos III de Madrid COV20/00110, ISCII

Low levels of granulocytic myeloid-derived suppressor cells may be a good marker of survival in the follow-up of patients with severe COVID-19

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died

Revisiting the epidemiology of bloodstream infections and healthcare-associated episodes: results from a multicentre prospective cohort in Spain (PRO-BAC Study)

PROBAC REIPI/GEIH-SEIMC/SAEI Group.The epidemiology of bloodstream infections (BSIs) is dynamic as it depends on microbiological, host and healthcare system factors. The aim of this study was to update the information regarding the epidemiology of BSIs in Spain considering the type of acquisition. An observational, prospective cohort study in 26 Spanish hospitals from October 2016 through March 2017 including all episodes of BSI in adults was performed. Bivariate analyses stratified by type of acquisition were performed. Multivariate analyses were performed by logistic regression. Overall, 6345 BSI episodes were included; 2510 (39.8%) were community-acquired (CA), 1661 (26.3%) were healthcare-associated (HCA) and 2056 (32.6%) hospital-acquired (HA). The 30-day mortality rates were 11.6%, 19.5% and 22.0%, respectively. The median age of patients was 71 years (interquartile range 60–81 years) and 3656 (58.3%; 95% confidence interval 57.1–59.6%) occurred in males. The proportions according to patient sex varied according to age strata. Escherichia coli (43.8%), Klebsiella spp. (8.9%), Staphylococcus aureus (8.9%) and coagulase-negative staphylococci (7.4%) were the most frequent pathogens. Multivariate analyses confirmed important differences between CA and HCA episodes, but also between HCA and HA episodes, in demographics, underlying conditions and aetiology. In conclusion, we have updated the epidemiological information regarding patients’ profiles, underlying conditions, frequency of acquisition types and aetiological agents of BSI in Spain. HCA is confirmed as a distinct type of acquisition.This work was financed by grants from Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades [PI16/01432] and the Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008], co‐financed by the European Development Regional Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Estudio prospectivo multicéntrico sobre bacteriemias que requieren tratamiento en UCI. Desarrollo y validación de un score pronóstico

INTRODUCCIÓN: La bacteriemia es una entidad clínica con una elevada incidencia e importante morbimortalidad. En este contexto, está descrito que los pacientes que desarrollan un episodio de bacteriemia que requiere ingreso en una unidad de cuidados intensivos (UCI), o bien adquiridas durante su estancia, presentan una estancia hospitalaria y una mortalidad más elevadas. Durante las últimas décadas los avances en el campo de la medicina han llevado a un importante incremento en la esperanza de vida. Sin embargo, esta mejora, no está libre de costes, el envejecimiento de la población está asociado con el incremento de comorbilidades y hospitalizaciones prolongadas y recurrentes. Todo ello conlleva que estemos asistiendo a un cambio en la epidemiología de las mismas, especialmente en lo que se refiere a factores de riesgo para su adquisición y perfil de resistencia de los microorganismos implicados, lo cual dificulta la elección del tratamiento antibiótico empírico condicionando el pronóstico de los pacientes. OBJETIVOS: • Describir las características epidemiológicas y clínicas de los pacientes con bacteriemias que requieren o no tratamiento en unidades de cuidados intensivos. • Analizar dichas diferencias en el subgrupo de pacientes con bacteriemias comunitarias (BC) y bacteriemias asociadas a cuidados sanitarios (BACS). • Definir y validar un score predictivo de mortalidad que sea fácil y práctico en su aplicación en el momento del diagnóstico, para los pacientes ingresados en unidades de cuidados intensivos. MÉTODOS: El proyecto PROBAC es un estudio observacional, prospectivo y multicéntrico nacional (26 centros participantes) de cohortes, coordinado desde el Hospital Universitario Virgen Macarena, diseñado para conocer los cambios epidemiológicos y clínicos relevantes que se han producido en los pacientes con bacteriemias y que pueden tener impacto en el manejo y pronóstico de los pacientes. En la cohorte PROBAC se incluyeron todos los episodios de bacteriemia detectados entre octubre de 2016 y abril de 2017 en los centros participantes de forma consecutiva, tanto de adquisición comunitaria, nosocomial o asociada a cuidados sanitarios. Se recogieron variables demográficas, microbiológicas y clínicas. Para la consecución de los objetivos del estudio, seguimos el siguiente esquema: • En primer lugar, se realizó un análisis descriptivo y comparativo de las características de los pacientes que precisaban tratamiento de la bacteriemia en UCI frente a los que no. • En segundo lugar, se realizó un análisis descriptivo y comparativo de los subgrupos de pacientes que presentaron una BC o una BACS. • Por último, para el cálculo del score predictivo se realizó un análisis multivariado utilizando modelos multivariantes de regresión logística en los que se incluyeron aquellas variables con asociación significativa en el análisis bivariante y las que se consideraron de interés clínico. La variable principal objetivo fue la mortalidad a los 30 días. Aquellas variables que mostraron un valor de p <0.05 en el modelo final se seleccionaron para el cálculo del score. El peso de cada variable se calculó dividiendo su coeficiente de regresión (coeficiente β) por la mitad del coeficiente más pequeño de las variables seleccionadas y redondeando al entero más próximo. Posteriormente, se examinó la capacidad de predicción del modelo calculando el área bajo la curva ROC (AUROC) respecto de los datos de la cohorte. RESULTADOS: En la base de datos PROBAC se incluyeron 6264 casos de bacteriemia procedente de 26 hospitales de la geografía española (16 de ellos hospitales de tercer nivel), durante un periodo de reclutamiento de seis meses consecutivos (octubre 2016-septiembre 2017). - Realizamos un análisis de toda la cohorte, comparando aquellos pacientes que requerían tratamiento del episodio de bacteriemia en UCI y aquellos que no. De la cohorte global que incluyó 6264 pacientes, 677 pacientes necesitaron del tratamiento del episodio de bacteriemia en UCI. Los pacientes con bacteriemias que precisaron ingreso en UCI fueron más jóvenes 67 (56-75) vs 70 (54-75) p<0.001, con índices pronósticos y scores de gravedad más elevados (Índice de Charlson: 4 (2-6) vs 4 (3-5); Índice de Pitt 1 (0-4) vs 0 (0-3); SOFA 3 (0-8) vs 1 (0-5) p < 0.001). Presentaron una menor carga de enfermedad fatal de base (McCabe) 36.8% vs 45.9% (p<0.001), más factores de riesgo extrínseco de infección [CVP: 44.2% vs 39.9% (p<0.05); CVC: 46.8% vs 14.9% (p<0.001); PICC: 9.7% vs 4.6% (p<0.001); VM en el mes previo 20.8% vs 2.3% (p<0.001)] y una mayor incidencia de bacteriemia de foco abdominal no biliar 16.1% vs 8% (p<0.001), relacionada con catéter 15.4% vs 12.3% (p<0.05) y de foco respiratorio tanto el asociado a neumonía 6.7% vs 4% (p=0.001); como el asociado a otras infecciones respiratorias 8% vs 4.2% (p<0.001), con mayor frecuencia de etiología por Gram-positivos 35.9% vs 29.9% (p<0.001). - A continuación, realizamos un análisis de aquellos pacientes que desarrollaron una BC. En la serie analizada detectamos 2503 episodios de BC lo cual supone un 40% de las bacteriemias, 237 precisaron de tratamiento en UCI, lo cual supone un 9.5% de los casos. Los pacientes con bacteriemias comunitarias que precisaron de ingreso en UCI en general tenían mayor gravedad clínica (Índice de Pitt >0 57.8% vs 28.7% p0 61.2% vs 36.5% p<0.001) y menor carga de enfermedad fatal de base (McCabe) McCabe 35% vs 23.6% p<0.001. Presentaron una mayor incidencia de bacteriemia de foco abdominal no biliar 12.3% vs 6.7% (OR 1.94 IC 95% 1.273-2.966), SNC 6.4% vs 0.8% (OR 8.23 IC 95% 4.092-16.560) y respiratorio tanto el asociado a neumonía 10.2% vs 4.9% (OR 2.21 IC 95% 1.392-3.526); como el asociado a otras infecciones respiratorias 9.3% vs 4.9% (OR 1.99 IC 95% 1.233-3.218), con mayor frecuencia de etiología por Gram-positivos 36.7% vs 23.8% (OR 1.85 IC 95% 1.399-2.456). - Realizamos un análisis similar al llevado a cabo en las BC para las BACS, en esta ocasión además contemplamos factores de riesgo relacionados con este tipo de infección. Se incluyeron 1634 episodios de BACS lo cual supone un 26% de los casos, de ellos un 0.5% (85 episodios), precisaron de tratamiento en UCI. Los pacientes con BACS que precisaron ingreso en UCI fueron en general pacientes con mayor gravedad clínica e índices pronósticos más elevados (Índice de Pitt >0 58.8% vs 32.1%; SOFA >0 62.4% vs 41.3%). Presentaron una mayor incidencia de bacteriemia de foco abdominal no biliar sin encontrar diferencias en los agentes etiológicos implicados 17.6% vs 7.2% (OR 2.77 IC 95% 1.534-4.995). - Incluimos los 677 pacientes que precisaron de tratamiento del episodio de bacteriemia en UCI en el análisis para el desarrollo y validación del modelo y score predictivo de mortalidad. Las variables con asociación significativa en el modelo final del score fueron: edad ≥ 75 años (2 puntos), APACHE II >18 (2 puntos), respuesta inflamatoria en forma de shock séptico (3 puntos), neoplasia (4 puntos), origen nosocomial (3 puntos), enfermedad hepática moderada o grave (3 puntos), e infección por S. aureus (2 puntos). Este modelo final presenta un AUROC para mortalidad de 0.76 (IC 95%: 0.71-0.80) en la cohorte de derivación y de 0.74 (IC95%: 0.67-0.80) en la cohorte de validación. CONCLUSIONES: En la población estudiada: - Los pacientes con bacteriemia que precisan de tratamiento en unidades de cuidados intensivos son más jóvenes, con unos índices pronósticos y scores de gravedad más elevados, una mayor incidencia de shock séptico como respuesta inflamatoria a la infección y una mortalidad más elevada. Dichas características se mantienen en la cohorte de bacteriemias comunitarias y bacteriemias asociadas a cuidados sanitarios. - En el subgrupo de las bacteriemias comunitarias que necesitan de tratamiento en unidades de cuidados intensivos, predomina el origen respiratorio con un predominio de microorganismos Gram-positivos (S. pneumoniae) mientras que en el resto de pacientes predomina el foco de origen desconocido y urinario con un predominio de microorganismos Gram-negativos. - Dentro de las bacteriemias asociadas a cuidados sanitarios, salvo una mayor incidencia de infección abdominal no biliar y las mencionadas previamente, no encontramos diferencias relevantes en cuanto a factores de riesgo extrínseco de infección, foco de infección y microbiología entre aquellos pacientes que precisan o no de tratamiento en unidades de cuidados intensivos. - Destaca la baja incidencia en nuestra serie de microorganismos multirresistentes tales como SAMR, E. coli productor de BLEE y Klebsiella spp. productor de BLEE, sin encontrar diferencias significativas entre ambas cohortes. Hecho que se mantiene en los subgrupos de Bacteriemias comunitarias y Bacteriemias asociadas a cuidados sanitarios. - El score predictivo de mortalidad que ha sido desarrollado y validado en esta tesis doctoral permite identificar pacientes con bajo, medio y alto riesgo de mortalidad con variables fácilmente medibles en el día que el paciente desarrolla la bacteriemia. - Entre los patógenos responsables, solo S. aureus aparece en el modelo del cual se deriva este score, lo cual refuerza la elevada gravedad de la bacteriemia causada por este microorganismo Gram-positivo

Higher frequency of comorbidities in fully vaccinated patients admitted to the ICU due to severe COVID-19: a prospective, multicentre, observational study

Severe COVID-19 disease requiring ICU admission is possible in the fully vaccinated population, especially in those with immunocompromised status and other comorbidities. Interventions to improve vaccine response might be necessary in this population

Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a disease (coronavirus disease 2019, COVID-19) that may develop into a systemic disease with immunosuppression and death in its severe form. Myeloid-derived suppressive cells (MDSCs) are inhibitory cells that contribute to immunosuppression in patients with cancer and infection. Increased levels of MDSCs have been found in COVID-19 patients, although their role in the pathogenesis of severe COVID-19 has not been clarified. For this reason, we raised the question whether MDSCs could be useful in the follow-up of patients with severe COVID-19 in the intensive care unit (ICU). Thus, we monitored the immunological cells, including MDSCs, in 80 patients admitted into the ICU. After 1, 2, and 3 weeks, we examined for a possible association with mortality (40 patients). Although the basal levels of circulating MDSCs did not discriminate between the two groups of patients, the last measurement before the endpoint (death or ICU discharge) showed that patients discharged alive from the ICU had lower levels of granulocytic MDSCs (G-MDSCs), higher levels of activated lymphocytes, and lower levels of exhausted lymphocytes compared with patients who had a bad evolution (death). In conclusion, a steady increase of G-MDSCs during the follow-up of patients with severe COVID-19 was found in those who eventually died

Pseudomonas aeruginosa Community-Onset Bloodstream Infections: Characterization, Diagnostic Predictors, and Predictive Score Development-Results from the PRO-BAC Cohort

Abstract Community-onset bloodstream infections (CO-BSI) caused by gram-negative bacilli are common and associated with significant mortality; those caused by Pseudomonas aeruginosa are associated with worse prognosis and higher rates of inadequateempirical antibiotic treatment. The aims of this study were to describe the characteristics of patients with CO-BSI caused by P. aeruginosa, to identify predictors, and to develop a predictive score for P. aeruginosa CO-BSI. Materials/methods: PROBAC is a prospective cohort including patients &gt;14 years with BSI from 26 Spanish hospitals between October 2016 and May 2017. Patients with monomicrobial P. aeruginosa CO-BSI and monomicrobial Enterobacterales CO-BSI were included. Variables of interest were collected. Independent predictors of Pseudomonas aeruginosa CO-BSI were identified by logistic regression and a prediction score was developed. Results: A total of 78patients with P. aeruginosa CO-BSI and 2572 with Enterobacterales CO-BSI were included. Patients with P. aeruginosa had a median age of 70 years (IQR 60-79), 68.8% were male, median Charlson score was 5 (IQR 3-7), and 30-daymortality was 18.5%. Multivariate analysis identified the following predictors of CO-BSI-PA [adjusted OR (95% CI)]: male gender [1.89 (1.14-3.12)], haematological malignancy [2.45 (1.20-4.99)], obstructive uropathy [2.86 (1.13-3.02)], source of infection other than urinary tract, biliary tract or intra-abdominal [6.69 (4.10-10.92)] and healthcare-associated BSI [1.85 (1.13-3.02)]. Anindex predictive of CO-BSI-PA was developed; scores ? 3.5 showed a negative predictive value of 89% and an area under the receiver operator curve (ROC) of 0.66. Conclusions: We did not find a good predictive score of P. aeruginosa CO-BSI due to its relatively low incidence in the overall population. Our model includes variables that are easy to collect in real clinical practice and could be useful to detect patients with very low risk of P. aeruginosa CO-BSI.This work was financed by grants from the Plan Nacional de I + D+i 2013–2016-Instituto de Salud Carlos III (Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades) [PI16/01432]; and Spanish Network for Research in Infectious Diseases (REIPI) [RD16/0016/0001; RD16/0016/0008]; co-financed by the European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020.Pseudomonas aeruginosaBacteraemiaBloodstream infectionCommunity-onsetEpidemiolog