Addressing current challenges in antibiotic treatment of community acquired pneumonia

Abstract

Community-acquired pneumonia (CAP) is the leading infectious cause of death and the fourth most common cause of global mortality in the world. The high incidence of CAP and the high burden of morbidity, mortality and their related costs have meant that research into CAP is among the most popular areas of investigation. Nowadays, although there has been important progress in CAP management, there are still controversial points and a great deal of room for improvement. Our investigation attempted to focus on some of the current challenges in CAP research. HYPOTHESIS 1. Mortality in community-acquired pneumonia might have decreased in recent years, and there could be certain factors related with this change. 2. Pre-hospital antibiotic treatments could have an impact on the etiology, clinical features and outcomes of patients hospitalized for community-acquired pneumonia. 3. Timing from admission to first dose of antibiotic administration could have an impact on 30-day mortality in patients with pneumonia. 4. Antibiotic de-escalation could be a safe and effective strategy in patients hospitalized with pneumococcal community-acquired pneumonia. 5. Hospitalized patients with community-acquired Legionella pneumonia would have different outcomes depending on the antibiotic treatment administered. 6. There could be differences in response to antibiotic treatment in community-acquired pneumonia based on multiple patient factors. In the first study: “Declining mortality among hospitalized patients with community-acquired pneumonia”, we found that: • Thirty-day mortality significantly decreased over time in hospitalized community-acquired pneumonia patients, despite an upward trend in patient age and other factors associated with poor outcomes. • Several changes in the management of community-acquired pneumonia and a general improvement in global care over time may have caused the observed outcomes. In the second study: “Impact of pre-hospital antibiotic use on community-acquired pneumonia”, we found that: • In our cohort, 17.3% of patients received pre-hospital antibiotic treatment. These patients were younger, with fewer comorbidities, and less frequently presented bacteraemia than those patients who had not received antibiotic before hospitalisation. • The prevalence of Legionella pneumophila was nearly three times higher in patients who received pre-hospital antibiotics, mainly those who received β-lactams. • Pre-hospital antibiotic use should be considered when choosing aetiological diagnostic tests and empirical antibiotic therapy in patients with community-acquired pneumonia. In the third study: “Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia”, we found that: • Patients receiving early treatment had significantly greater illness severity at admission. • Antibiotic administration within 4 or 8 hours of arrival at the emergency department did not improve rates of 30-day survival in hospitalized adults for community-acquired pneumonia or healthcare-associated pneumonia. In the fourth study: “Impact of antibiotic de-escalation on clinical outcomes in community-acquired pneumococcal pneumonia”, we found that: • Antibiotic de-escalation appears to be safe and effective in reducing the duration of hospital stay. • Antibiotic de-escalation did not adversely affect outcomes of patients with community-acquired pneumococcal penumonia, even those with bacteraemia and severe disease, and those who were clinically unstable at time of de-escalation. • De-escalation strategies should be more widely implemented in the management of hospitalized adults with community-acquired pneumococcal penumonia. In the fifth study: “Levofloxacin versus azithromycin for treating Legionella pneumonia: a propensity score analysis”, we found that: • No significant differences in relevant outcomes were found between patients with Legionella pneumonia treated with levofloxacin and those receiving azithromycin. In the sixth study: “Predictors for individual patient antibiotic treatment effect in hospitalised community-acquired pneumonia patients”, we found that: • Older age and smoking could influence the response to specific antibiotic regimens. • The effect modification of age and smoking should be considered as a hypothesis to be evaluated in future trials.

La neumonía adquirida en la comunidad (NAC) es la principal causa infecciosa de mortalidad en el mundo. Existen todavía puntos controvertidos en el abordaje terapéutico de la NAC. En este contexto se desarrolla la presente tesis doctoral. El primer estudio, encontró una disminución sustancial en la mortalidad a 30 días durante un período de 20 años, a pesar de una tendencia al alza en varios factores con influencia pronóstica negativa. Se observaron importantes cambios en el abordaje de los pacientes de la NAC, como el aumento de uso de ventilación mecánica, ingresos en la Unidad de Cuidados Intensivos, y el uso de fluoroquinolonas. Estos cambios pudieron ser la causa de la disminución de mortalidad observada. En el segundo estudio sobre el impacto del tratamiento antibiótico previo al ingreso, los pacientes con tratamiento antibiótico previo eran más jóvenes, con menor comorbilidad, fueron menos propensos a tener fiebre, leucocitosis y bacteriemia, y en ellos la prevalencia de Legionella pneumophila fue casi tres veces mayor. En el tercer estudio se encontró que la administración de antibióticos dentro de las primeras 4-8 horas de la llegada a Urgencias no mejoró la supervivencia a los 30 días en los adultos hospitalizados para NAC o neumonía relacionada con el ámbito sanitario. En el cuarto estudio sobre la desescalada de antibióticos en pacientes con neumonía neumocócica, la desescalada no se asoció a aumento de mortalidad y fue eficaz para reducir la duración de la estancia hospitalaria, incluso en los pacientes con bacteriemia, enfermedad grave, o los que estaban clínicamente inestables al momento de desescalar. En un estudio multicéntrico que valoró el tratamiento antibiótico en la neumonía por Legionella, los pacientes tratados con azitromicina tuvieron resultados similares a los tratados con levofloxacino, mientras los pacientes tratados con claritromicina tuvieron una estancia hospitalaria más prolongada. No se encontraron diferencias entre los tratamientos en cuanto a la mortalidad a los 30 días. En el sexto estudio, se analizaron predictores clínicos de respuesta a tratamiento antibiótico empírico. La edad avanzada y el tabaquismo se asocian con una mayor mortalidad a los 30 días en pacientes que recibieron fluoroquinolonas; la edad avanzada se relacionó también con una mayor estancia hospitalaria en los pacientes que recibieron beta-lactamicos + macrolidos.