Antibioticoterapia empírica en la neumonía comunitaria grave: impacto sobre la mortalidad tras la administración de dos antibióticos de forma precoz

La neumonía comunitaria es una enfermedad que representa un problema sanitario significativo que se asocia a elevada mortalidad y morbilidad. En el mundo occidental, pese a un aumento global de la supervivencia gracias al cambio de las políticas antibióticas, se ha documentado mayor mortalidad en pacientes mayores y en pacientes con comorbilidades y enfermedades crónicas. Por otro lado, se ha demostrado como la mortalidad por shock séptico y otras enfermedades graves ha disminuido. El impacto total de estos cambios demográficos y clínicos en la supervivencia en la neumonía comunitaria es de elevada importancia para los clínicos, pero no hay datos recientes publicados en la literatura. Nuestra hipótesis fue que la mejora de las políticas antibióticas contribuyó a disminuir la mortalidad en la neumonía comunitaria grave en pacientes admitidos en la UCI. Por esto, el objetivo primario fue comparar la mortalidad en UCI de pacientes ingresados en UCI, procedentes de dos periodos diferentes. El objetivo secundario fue buscar una asociación entre tratamiento antibiótico combinado y disminución de la mortalidad. Objetivo terciario fue buscar una asociación entre antibioticoterapia empírica precoz y disminución de la mortalidad. El estudio CAPUCI I es un estudio multicéntrico, prospectivo y observacional realizado en 33 hospitales de España desde 2000 hasta 2002. Todos los paciente fueron ingresados en la UCI con diagnostico de neumonía comunitaria grave. El estudio CAPUCI II es un estudio de seguimiento del CAPUCI I apoyado por la European Critical Care Research Network. El estudio se llevó a cabo en 29 UCIs de Europa, desde 2008 hasta 2014. En ambos estudios, los pacientes eran admitidos en UCI por necesidad de ventilación mecánica invasiva, presencia de shock séptico o por una situación de inestabilidad clínica. El trabajo se realizó mediante la publicación de dos artículos científicos. En el primer estudio caso-control, titulado: "Decrease in Mortality in Severe Community- Acquired Pneumococcal Pneumonia: Impact of Improving Antibiotic Strategies (2000-2013)"; ochenta pacientes diagnosticados de neumonía neumocócica severa comunitaria del estudio CAPUCI II fueron apareados con 80 del CAPUCI I a partir de las siguientes variables: shock, ventilación mecánica, COPD, inmunosupresión y edad. Entre los resultados, el tratamiento combinado aumento desde 66.2% en el estudio CAPUCI I hasta 87.5% en el CAPUCI II, y el percentil de pacientes que recibieron antibioticoterapia las primeras 3 horas de admisión pasó desde 27.5% hasta 70.0%. La mortalidad en UCI fue significativamente inferior en el grupo CAPUCI II. En el análisis multivariado, la mortalidad aumentó en pacientes que necesitaron ventilación mecánica y disminuyó en pacientes que recibieron tratamiento antibiótico combinado y antibioticoterapia precoz. El segundo articulo tiene como titulo: "Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study". Es un estudio caso-control que incluye 144 pacientes con neumonía grave no neumocócica: 72 pacientes del estudio CAPUCI I fueron apareados con 72 del CAPUCI II a través de las siguientes variables: microorganismo, shock, ventilación mecánica, COPD y edad. Se observó una reducción absoluta de la mortalidad en UCI entre los dos grupos. Además, el tratamiento combinado y antibioticoterapia precoz fueron significativamente mayores en el estudio CAPUCI II (76.4% frente a 90.3 % y 37.5% frente a 63.9 %). En el análisis multivariado la administración de tratamiento antibiótico combinado y antibioticoterapia precoz se asociaron a disminución de la mortalidad en UCI. En conclusión, el presente trabajo de tesis documenta una reducción de la mortalidad por neumonía comunitaria grave entre los dos periodos a estudio. Además, la administración de tratamiento combinado y precoz se asocia a disminución de mortalidad en UCI.Community-acquired pneumonia is a major health problem associated with high morbidity and mortality. In Western countries, despite improved survival due to changes in antibiotic policies, poor prognosis is seen in older people with more comorbidities and chronic illness in whom life expectancy has been prolonged. On the other hand, it has been shown that septic shock mortality and mortality due to other severe diseases have decreased. The aggregate impact of these demographic and clinical trends on the community pneumonia survival rate is of great importance to clinicians, but no recent data are available in the literature, especially in critical patients with severe community-acquired pneumonia. Our hypothesis was that improvement in antibiotic policies contributed to reduce mortality due to severe community-acquired pneumonia in the ICU setting. For this reason, the primary objective of the present study was to compare ICU mortality due to severe community pneumonia in two different periods. Secondary objective was to identify an association between combination antibiotic therapy and decreased mortality. Tertiary objective was to identify an association between early antibiotic administration and decreased mortality. CAPUCI I was a multicenter, prospective, observational study carried out in 33 hospitals in Spain between 2000 and 2002. All patients admitted to ICU with diagnosis of severe community pneumonia were included. CAPUCI II was a follow-up Project endorsed by the European Critical Care Research Network, carried out in 29 European ICUs from 2008 to 2014. In both studies, patients were admitted to the ICU either to undergo IMV or because they were in an unstable clinical condition. All cases were followed until ICU discharge or death, and all clinical decisions were left to the discretion of the attending physician. The present manuscript was carried out after publication of two papers. The first one is a case control study titled: "Decrease in Mortality in Severe Community-Acquired Pneumococcal Pneumonia: Impact of Improving Antibiotic Strategies (2000-2013)"; eighty patients diagnosed with severe pneumococcal community pneumonia from the CAPUCI II study were matched with 80 patients from CAPUCI I based on the following: shock at admission, need of mechanical ventilation, COPD, immunosuppression, and age. As a result, combined antibiotic therapy increased from 66.2% in CAPUCI I to 87.5% in CAPUCI II, and the percentage of patients receiving the first dose of antibiotic within 3 h increased from 27.5% to 70.0%. ICU mortality was significantly lower in CAPUCI II group. In the multivariate analysis, ICU mortality increased in patients requiring mechanical ventilation and decreased in patients receiving early antibiotic treatment and combined therapy. The second article was titled: "Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study". This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the CAPUCI I database were paired with 72 from the CAPUCI II matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. Again, we observed an absolute reduction of mortality between the two groups. Moreover, combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3 % and 37.5 versus 63.9 %). In the multivariate analysis, combined antibiotic therapy and early antibiotic treatment were independently associated with decreased intensive care unit mortality. In conclusion, the present manuscript observed an absolute reduction of ICU mortality in patients with community-acquired pneumonia between the two study periods. Moreover, early combination antibiotic therapy was associated with decreased mortality

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study

INTRODUCTION: We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000-2002 and 2008-2014, and the impact of the improvement in antibiotic strategies on outcomes. METHODS: This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000-2002 database (CAPUCI I group) were paired with 72 from the 2008-2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. RESULTS: The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1%) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7%); prevalence of shock was 59.7%, while 73.6% of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7% versus 16.7%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5% in CAPUCI I and 92.7% in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3% and 37.5 versus 63.9%; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95% CI 0.07-0.74) and early antibiotic treatment (OR 0.07, 95% CI 0.02-0.22) were independently associated with decreased intensive care unit mortality. CONCLUSIONS: In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period

Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia

Purpose This study aimed at investigating the mechanisms underlying the oxygenation response to proning and recruitment maneuvers in coronavirus disease 2019 (COVID-19) pneumonia. Methods Twenty-five patients with COVID-19 pneumonia, at variable times since admission (from 1 to 3 weeks), underwent computed tomography (CT) lung scans, gas-exchange and lung-mechanics measurement in supine and prone positions at 5 cmH(2)O and during recruiting maneuver (supine, 35 cmH(2)O). Within the non-aerated tissue, we differentiated the atelectatic and consolidated tissue (recruitable and non-recruitable at 35 cmH(2)O of airway pressure). Positive/negative response to proning/recruitment was defined as increase/decrease of PaO2/FiO(2). Apparent perfusion ratio was computed as venous admixture/non aerated tissue fraction. Results The average values of venous admixture and PaO2/FiO(2) ratio were similar in supine-5 and prone-5. However, the PaO2/FiO(2) changes (increasing in 65% of the patients and decreasing in 35%, from supine to prone) correlated with the balance between resolution of dorsal atelectasis and formation of ventral atelectasis (p = 0.002). Dorsal consolidated tissue determined this balance, being inversely related with dorsal recruitment (p = 0.012). From supine-5 to supine-35, the apparent perfusion ratio increased from 1.38 +/- 0.71 to 2.15 +/- 1.15 (p = 0.004) while PaO2/FiO(2) ratio increased in 52% and decreased in 48% of patients. Non-responders had consolidated tissue fraction of 0.27 +/- 0.1 vs. 0.18 +/- 0.1 in the responding cohort (p = 0.04). Consolidated tissue, PaCO2 and respiratory system elastance were higher in patients assessed late (all p < 0.05), suggesting, all together, "fibrotic-like" changes of the lung over time. Conclusion The amount of consolidated tissue was higher in patients assessed during the third week and determined the oxygenation responses following pronation and recruitment maneuvers

Antibioticoterapia empírica en la neumonía comunitaria grave: impacto sobre la mortalidad tras la administración de dos antibióticos de forma precoz

La neumonía comunitaria es una enfermedad que representa un problema sanitario significativo que se asocia a elevada mortalidad y morbilidad. En el mundo occidental, pese a un aumento global de la supervivencia gracias al cambio de las políticas antibióticas, se ha documentado mayor mortalidad en pacientes mayores y en pacientes con comorbilidades y enfermedades crónicas. Por otro lado, se ha demostrado como la mortalidad por shock séptico y otras enfermedades graves ha disminuido. El impacto total de estos cambios demográficos y clínicos en la supervivencia en la neumonía comunitaria es de elevada importancia para los clínicos, pero no hay datos recientes publicados en la literatura. Nuestra hipótesis fue que la mejora de las políticas antibióticas contribuyó a disminuir la mortalidad en la neumonía comunitaria grave en pacientes admitidos en la UCI. Por esto, el objetivo primario fue comparar la mortalidad en UCI de pacientes ingresados en UCI, procedentes de dos periodos diferentes. El objetivo secundario fue buscar una asociación entre tratamiento antibiótico combinado y disminución de la mortalidad. Objetivo terciario fue buscar una asociación entre antibioticoterapia empírica precoz y disminución de la mortalidad. El estudio CAPUCI I es un estudio multicéntrico, prospectivo y observacional realizado en 33 hospitales de España desde 2000 hasta 2002. Todos los paciente fueron ingresados en la UCI con diagnostico de neumonía comunitaria grave. El estudio CAPUCI II es un estudio de seguimiento del CAPUCI I apoyado por la European Critical Care Research Network. El estudio se llevó a cabo en 29 UCIs de Europa, desde 2008 hasta 2014. En ambos estudios, los pacientes eran admitidos en UCI por necesidad de ventilación mecánica invasiva, presencia de shock séptico o por una situación de inestabilidad clínica. El trabajo se realizó mediante la publicación de dos artículos científicos. En el primer estudio caso-control, titulado: “Decrease in Mortality in Severe Community- Acquired Pneumococcal Pneumonia: Impact of Improving Antibiotic Strategies (2000-2013)”; ochenta pacientes diagnosticados de neumonía neumocócica severa comunitaria del estudio CAPUCI II fueron apareados con 80 del CAPUCI I a partir de las siguientes variables: shock, ventilación mecánica, COPD, inmunosupresión y edad. Entre los resultados, el tratamiento combinado aumento desde 66.2% en el estudio CAPUCI I hasta 87.5% en el CAPUCI II, y el percentil de pacientes que recibieron antibioticoterapia las primeras 3 horas de admisión pasó desde 27.5% hasta 70.0%. La mortalidad en UCI fue significativamente inferior en el grupo CAPUCI II. En el análisis multivariado, la mortalidad aumentó en pacientes que necesitaron ventilación mecánica y disminuyó en pacientes que recibieron tratamiento antibiótico combinado y antibioticoterapia precoz. El segundo articulo tiene como titulo: “Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case–control study“. Es un estudio caso-control que incluye 144 pacientes con neumonía grave no neumocócica: 72 pacientes del estudio CAPUCI I fueron apareados con 72 del CAPUCI II a través de las siguientes variables: microorganismo, shock, ventilación mecánica, COPD y edad. Se observó una reducción absoluta de la mortalidad en UCI entre los dos grupos. Además, el tratamiento combinado y antibioticoterapia precoz fueron significativamente mayores en el estudio CAPUCI II (76.4% frente a 90.3 % y 37.5% frente a 63.9 %). En el análisis multivariado la administración de tratamiento antibiótico combinado y antibioticoterapia precoz se asociaron a disminución de la mortalidad en UCI. En conclusión, el presente trabajo de tesis documenta una reducción de la mortalidad por neumonía comunitaria grave entre los dos periodos a estudio. Además, la administración de tratamiento combinado y precoz se asocia a disminución de mortalidad en UCI.Community-acquired pneumonia is a major health problem associated with high morbidity and mortality. In Western countries, despite improved survival due to changes in antibiotic policies, poor prognosis is seen in older people with more comorbidities and chronic illness in whom life expectancy has been prolonged. On the other hand, it has been shown that septic shock mortality and mortality due to other severe diseases have decreased. The aggregate impact of these demographic and clinical trends on the community pneumonia survival rate is of great importance to clinicians, but no recent data are available in the literature, especially in critical patients with severe community-acquired pneumonia. Our hypothesis was that improvement in antibiotic policies contributed to reduce mortality due to severe community-acquired pneumonia in the ICU setting. For this reason, the primary objective of the present study was to compare ICU mortality due to severe community pneumonia in two different periods. Secondary objective was to identify an association between combination antibiotic therapy and decreased mortality. Tertiary objective was to identify an association between early antibiotic administration and decreased mortality. CAPUCI I was a multicenter, prospective, observational study carried out in 33 hospitals in Spain between 2000 and 2002. All patients admitted to ICU with diagnosis of severe community pneumonia were included. CAPUCI II was a follow-up Project endorsed by the European Critical Care Research Network, carried out in 29 European ICUs from 2008 to 2014. In both studies, patients were admitted to the ICU either to undergo IMV or because they were in an unstable clinical condition. All cases were followed until ICU discharge or death, and all clinical decisions were left to the discretion of the attending physician. The present manuscript was carried out after publication of two papers. The first one is a case control study titled: “Decrease in Mortality in Severe Community-Acquired Pneumococcal Pneumonia: Impact of Improving Antibiotic Strategies (2000-2013)”; eighty patients diagnosed with severe pneumococcal community pneumonia from the CAPUCI II study were matched with 80 patients from CAPUCI I based on the following: shock at admission, need of mechanical ventilation, COPD, immunosuppression, and age. As a result, combined antibiotic therapy increased from 66.2% in CAPUCI I to 87.5% in CAPUCI II, and the percentage of patients receiving the first dose of antibiotic within 3 h increased from 27.5% to 70.0%. ICU mortality was significantly lower in CAPUCI II group. In the multivariate analysis, ICU mortality increased in patients requiring mechanical ventilation and decreased in patients receiving early antibiotic treatment and combined therapy. The second article was titled: “Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case–control study“. This was a matched case–control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the CAPUCI I database were paired with 72 from the CAPUCI II matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. Again, we observed an absolute reduction of mortality between the two groups. Moreover, combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3 % and 37.5 versus 63.9 %). In the multivariate analysis, combined antibiotic therapy and early antibiotic treatment were independently associated with decreased intensive care unit mortality. In conclusion, the present manuscript observed an absolute reduction of ICU mortality in patients with community-acquired pneumonia between the two study periods. Moreover, early combination antibiotic therapy was associated with decreased mortality

Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia

Objetivo: Valorar tasa de adherencia y causas de no adherencia a las guías terapéuticas internacionales para la prescripción antibiótica empírica en la neumonía grave en Latinoamérica. Métodos: Encuesta clínica realizada a 36 médicos de Latinoamérica donde se pedía indicar el tratamiento empírico en 2 casos clínicos ficticios de pacientes con infección respiratoria grave: neumonía adquirida en la comunidad y neumonía nosocomial. Resultados: En el caso de la neumonía comunitaria el tratamiento fue adecuado en el 30,6% de las prescripciones. Las causas de no adherencia fueron monoterapia (16,0%), cobertura no indicada para multirresistentes (4,0%) y empleo de antibióticos con espectro inadecuado (44,0%). En el caso de la neumonía nosocomial el cumplimiento de las guías terapéuticas Infectious Disease Society of America/American Thoracic Society fue del 2,8%. Las causas de falta de adherencia fueron monoterapia (14,3%) y la falta de doble tratamiento antibiótico frente a Pseudomonas aeruginosa (85,7%). En caso de considerar correcta la monoterapia con actividad frente a P. aeruginosa, el tratamiento sería adecuado en el 100% de los casos. Conclusión: En la neumonía comunitaria la adherencia a las guías terapéuticas Infectious Disease Society of America/American Thoracic Society fue del 30,6%; la causa más frecuente de incumplimiento fue el uso de monoterapia. La adherencia en el caso de la neumonía nosocomial fue del 2,8% y la causa más importante de incumplimiento fue la falta de doble tratamiento frente a P. aeruginosa, considerando adecuada monoterapia con actividad frente a P. aeruginosa la adherencia sería del 100%

End-tidal to arterial PCO2 ratio: a bedside meter of the overall gas exchanger performance

Background!#!The physiological dead space is a strong indicator of severity and outcome of acute respiratory distress syndrome (ARDS). The 'ideal' alveolar PCO!##!Results!#!We retrospectively studied 200 patients with ARDS. The source was a database in which we collected since 2003 all the patients enrolled in different CT scan studies. The P!##!Conclusion!#!The ratio

Prone position: how understanding and clinical application of a technique progress with time

Abstract Historical background The prone position was first proposed on theoretical background in 1974 (more advantageous distribution of mechanical ventilation). The first clinical report on 5 ARDS patients in 1976 showed remarkable improvement of oxygenation after pronation.  Pathophysiology The findings in CT scans enhanced the use of prone position in ARDS patients. The main mechanism of the improved gas exchange seen in the prone position is nowadays attributed to a dorsal ventilatory recruitment, with a substantially unchanged distribution of perfusion. Regardless of the gas exchange, the primary effect of the prone position is a more homogenous distribution of ventilation, stress and strain, with similar size of pulmonary units in dorsal and ventral regions. In contrast, in the supine position the ventral regions are more expanded compared with the dorsal regions, which leads to greater ventral stress and strain, induced by mechanical ventilation. Outcome in ARDS The number of clinical studies paralleled the evolution of the pathophysiological understanding. The first two clinical trials in 2001 and 2004 were based on the hypothesis that better oxygenation would lead to a better survival and the studies were more focused on gas exchange than on lung mechanics. The equations better oxygenation = better survival was disproved by these and other larger trials (ARMA trial). However, the first studies provided signals that some survival advantages were possible in a more severe ARDS, where both oxygenation and lung mechanics were impaired. The PROSEVA trial finally showed the benefits of prone position on mortality supporting the thesis that the clinical advantages of prone position, instead of improved gas exchange, were mainly due to a less harmful mechanical ventilation and better distribution of stress and strain. In less severe ARDS, in spite of a better gas exchange, reduced mechanical stress and strain, and improved oxygenation, prone position was ineffective on outcome. Prone position and COVID-19 The mechanisms of oxygenation impairment in early COVID-19 are different than in typical ARDS and relate more on perfusion alteration than on alveolar consolidation/collapse, which are minimal in the early phase. Bronchial shunt may also contribute to the early COVID-19 hypoxemia. Therefore, in this phase, the oxygenation improvement in prone position is due to a better matching of local ventilation and perfusion, primarily caused by the perfusion component. Unfortunately, the conditions for improved outcomes, i.e. a better distribution of stress and strain, are almost absent in this phase of COVID-19 disease, as the lung parenchyma is nearly fully inflated. Due to some contradictory results, further studies are needed to better investigate the effect of prone position on outcome in COVID-19 patients. Graphical Abstrac

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study

INTRODUCTION: We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000-2002 and 2008-2014, and the impact of the improvement in antibiotic strategies on outcomes. METHODS: This was a matched case-control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000-2002 database (CAPUCI I group) were paired with 72 from the 2008-2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. RESULTS: The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1%) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7%); prevalence of shock was 59.7%, while 73.6% of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7% versus 16.7%; odds ratio (OR) 0.78, 95% confidence interval (CI) 0.64-0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5% in CAPUCI I and 92.7% in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3% and 37.5 versus 63.9%; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95% CI 0.07-0.74) and early antibiotic treatment (OR 0.07, 95% CI 0.02-0.22) were independently associated with decreased intensive care unit mortality. CONCLUSIONS: In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period