A prospective study of lung disease in a cohort of early rheumatoid arthritis patients.

Lung disease is common in patients with rheumatoid arthritis (RA). The onset of lung involvement in RA is not well known. The objective is to describe the features and evolution of lung involvement in early RA, its relationship with disease activity parameters, smoking and treatments. Consecutive patients with early RA without respiratory symptoms were included and tracked for 5 years. Lung assessment included clinical, radiological and pulmonary function tests at diagnosis and during follow-up. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti-citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS28-CRP, were evaluated. 40 patients were included and 32 completed the 5-year follow up. 13 patients presented lung involvement in the initial 5 years after RA diagnosis, 3 of them interstitial lung disease. Significant decrease of diffusion lung transfer capacity of carbon monoxide over time was observed in six patients, 2 of them developed interstitial lung disease. DLCO decrease was correlated with higher values of CRP and ESR at diagnosis. Methotrexate was not associated with DLCO deterioration or lung disease development. Subclinical progressive lung disease correlates with RA activity parameters. Smoking status and methotrexate were not associated with development or progression of lung disease.

Consenso multidisciplinar sobre prevención y tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. Adaptación al paciente dermatológico / Prevention and treatment of tuberculosis infection in candidates for biologic therapy: A multidisciplinary consensus statement adapted to the dermatology patient

El riesgo de infección por Mycobacterium tuberculosis se halla aumentado en los pacientes con enfermedades inflamatorias crónicas y en tratamiento inmunosupresor, en particular con terapia antifactor de necrosis tumoral α. La detección de la infección tuberculosa latente y el tratamiento preventivo dirigido a reducir el riesgo de progresión a tuberculosis activa es obligatoria en este grupo de pacientes. Este documento de consenso multidisciplinar actualiza la opinión de expertos y establece recomendaciones para el diagnóstico y tratamiento de la infección tuberculosa latente en estos pacientes, según los conocimientos actuales en terapias biológicas

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents

Prevention and treatment of tuberculosis infection in candidates for biologic therapy: A multidisciplinary consensus statement adapted to the dermatology patient. / Consenso multidisciplinar sobre prevención y tratamiento de la tuberculosis en pacientes candidatos a tratamiento biológico. Adaptación al paciente dermatológico.

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents.

Anti-fibrotic effects of pirfenidone and rapamycin in primary IPF fibroblasts and human alveolar epithelial cells.

BACKGROUND: Pirfenidone, a pleiotropic anti-fibrotic treatment, has been shown to slow down disease progression of idiopathic pulmonary fibrosis (IPF), a fatal and devastating lung disease. Rapamycin, an inhibitor of fibroblast proliferation could be a potential anti-fibrotic drug to improve the effects of pirfenidone. METHODS: Primary lung fibroblasts from IPF patients and human alveolar epithelial cells (A549) were treated in vitro with pirfenidone and rapamycin in the presence or absence of transforming growth factor ß1 (TGF-ß). Extracellular matrix protein and gene expression of markers involved in lung fibrosis (tenascin-c, fibronectin, collagen I [COL1A1], collagen III [COL3A1] and α-smooth muscle actin [α-SMA]) were analyzed. A cell migration assay in pirfenidone, rapamycin and TGF-ß-containing media was performed. RESULTS: Gene and protein expression of tenascin-c and fibronectin of fibrotic fibroblasts were reduced by pirfenidone or rapamycin treatment. Pirfenidone-rapamycin treatment did not revert the epithelial to mesenchymal transition pathway activated by TGF-ß. However, the drug combination significantly abrogated fibroblast to myofibroblast transition. The inhibitory effect of pirfenidone on fibroblast migration in the scratch-wound assay was potentiated by rapamycin combination. CONCLUSIONS: These findings indicate that the combination of pirfenidone and rapamycin widen the inhibition range of fibrogenic markers and prevents fibroblast migration. These results would open a new line of research for an anti-fibrotic combination therapeutic approach.

Increasing isolation of rapidly growing mycobacteria in a low-incidence setting of environmental mycobacteria, 1994-2015.

To determine trends in incidence and clinical relevance of rapidly growing mycobacteria (RGM) in a low-prevalence region of non-tuberculous mycobacteria. We retrospectively identified all patients with RGM-positive cultures between January 1994 and December 2015. Trends in incidence, clinical significance, and outcomes were assessed. One hundred and forty patients had RGM-positive cultures (116 respiratory and 24 extra-respiratory sources). The incidence of RGM isolates increased steadily from 2003 (0.34 per 100,000) to 2015 (1.73 per 100,000), with an average annual increase of 8.3%. Thirty-two patients (22.9%) had clinical disease, which trended to cluster in the second half of the study period. A positive acid-fast bacilli smear (odds ratio [OR] 97.7, 95 % CI 13.8-689.4), the presence of extra-respiratory isolates (OR 19.4, 95 % CI 5.2-72.7), and female gender (OR 5.9, 95 % CI 1.9-19.1) were independently associated with clinical disease. Cure rates were 73.3 and 87.5% for pulmonary and extra-pulmonary disease respectively. Although the burden of disease remains low, the presence of RGM isolates is increasing in our geographical setting. Whether this rise will be sustained over time and will coincide with an increase in clinical disease, or whether it is merely a cycle in the poorly understood epidemiological behaviour of environmental mycobacteria, will be seen in the near future.

XVI Congreso SEINAP. Proteínas parcialmente hidrolizadas / XVI Congreso SEINAP. Partiatilly hydrolysed proteins

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Aberrant gene methylation and bronchial dysplasia in high risk lung cancer patients.

INTRODUCTION: The risk for lung cancer is incremented in high degree dysplasia (HGD) and in subjects with hypermethylation of multiple genes. We sought to establish the association between them, as well as to analyze the DNA aberrant methylation in sputum and in bronchial washings (BW). METHODS: Cross sectional study of high risk patients for lung cancer in whom induced sputum and autofluorescence bronchoscopy were performed. The molecular analysis was determined on DAPK1, RASSF1A and p16 genes using Methylation-specific PCR. RESULTS: A total of 128 patients were enrolled in the study. Dysplasia lesions were found in 79 patients (61.7%) and high grade dysplasia in 20 (15.6%). Ninety eight patients out of 128 underwent molecular analysis. Methylation was observed in bronchial secretions (sputum or BW) in 60 patients (61.2%), 51 of them (52%) for DAPK1, in 20 (20.4%) for p16 and in three (3.1%) for RASSF1A. Methylated genes only found in sputum accounted for 38.3% and only in BW in 41.7%, and in both 20.0%. In the 11.2% of the patients studied, HGD and a hypermethylated gene were present, while for the 55.1% of the sample only one of both was detected and for the rest of the subjects (33.6%), none of the risk factors were observed. CONCLUSIONS: Our data determines DNA aberrant methylation panel in bronchial secretions is present in a 61.2% and HGD is found in 15.6%. Although both parameters have previously been identified as risk factors for lung cancer, the current study does not find a significative association between them. The study also highlights the importance of BW as a complementary sample to induced sputum when analyzing gene aberrant methylation.

Declining mortality among hospitalized patients with community-acquired pneumonia.

Little information is available on the changes over time in community-acquired pneumonia (CAP) management and their impact on 30-day mortality in hospitalized patients. We performed a prospective, observational study of non-severely immunosuppressed hospitalized adults with CAP from 1995 to 2014. A total of 4558 patients were included. Thirty-day mortality decreased from 9.6% in the first study period (1995-99) to 4.1% in the last period (2010-14); with a progressive downward trend (-0.2% death/year; p for trend = 0.003). Over time, patients were older (p 0.02), had more co-morbidities (p 0.037), more frequently presented severe illness according to the Pneumonia Severity Index (p <0.001) and septic shock (p <0.001), and more often required intensive care unit admission (p <0.001). Combination antibiotic therapy (p <0.001) and fluoroquinolone use (p <0.001) increased. Factors independently associated with 30-day mortality were increasing age (OR 1.04; 95% CI 1.03-1.05), co-morbidities (OR 1.48; 95% CI 1.04-2.11), shock at admission (OR 4.95; 95% CI 3.49-7.00), respiratory failure (OR 1.89; 95% CI 1.42-2.52), bacteraemia (OR 2.16; 95% CI 1.58-2.96), Gram-negative bacilli aetiology (OR 4.79; 95% CI 2.52-9.10) and fluoroquinolone use (OR 0.45; 95% CI 0.29-0.71). When we adjusted for a propensity score to receive fluoroquinolones, the protective effect of fluoroquinolone use was not confirmed. In conclusion, 30-day mortality decreased significantly over time in hospitalized patients with CAP in spite of an upward trend in patient age and other factors associated with poor outcomes. Several changes in the management of CAP and a general improvement in global care over time may have caused the observed outcomes.

Prognostic factors for relapse in stage I seminoma: a new nomogram derived from three consecutive, risk-adapted studies from the Spanish Germ Cell Cancer Group (SGCCG).

BACKGROUND: We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups. PATIENTS AND METHODS: From 1994 to 2008, 744 patients were included in three consecutive, prospective risk-adapted studies by the Spanish Germ Cell Cancer Group. Low-risk patients were managed by surveillance and high-risk patients were given two courses of adjuvant carboplatin. Relapses were treated mainly with chemotherapy. Patient age, tumor size, histological variant, pT staging, rete testis invasion, and preoperative serum BHCG levels were assessed for prediction of disease-free survival (DFS). RESULTS: After a median follow-up of 80 months, 63 patients (11.1%) have relapsed: 51/396 (14.8%) on surveillance and 12/348 (3.2%) following adjuvant carboplatin. Actuarial overall 5-year DFS was 92.3% (88.3% for surveillance versus 96.8% for chemotherapy, P = 0.0001). Median time to relapse was 14 months. Most recurrences were located at retroperitoneum (86%), with a median tumor size of 26 mm. All patients were rendered disease-free with chemotherapy (92%), radiotherapy (5%), or surgery followed by chemotherapy (3%). A nomogram was developed from surveillance patients that includes two independent, predictive factors for relapse: rete testis invasion and tumor size (as a continuous variable). CONCLUSION: Long-term follow-up confirms the risk-adapted approach as an effective option for patients with stage I seminoma. The pattern of relapses after adjuvant chemotherapy is similar to that observed following surveillance. A new nomogram for prediction of DFS among patients on surveillance is proposed. Rete testis invasion and tumor size should be taken into account when considering the administration of adjuvant carboplatin. Prospective validation is warranted.

Impact of pre-hospital antibiotic use on community-acquired pneumonia.

Information on the influence of pre-hospital antibiotic treatment on the causative organisms, clinical features and outcomes of patients with community-acquired pneumonia (CAP) remains scarce. We performed an observational study of a prospective cohort of non-immunosuppressed adults hospitalized with CAP between 2003 and 2012. Patients were divided into two groups: those who had received pre-hospital antibiotic treatment for the same episode of CAP and those who had not. A propensity score was used to match patients. Of 2179 consecutive episodes of CAP, 376 (17.3%) occurred in patients who had received pre-hospital antibiotic treatment. After propensity score matching, Legionella pneumophila was more frequently identified in patients with pre-hospital antibiotic treatment, while Streptococcus pneumoniae was less common (p <0.001 and p <0.001, respectively). Bacteraemia was less frequent in pre-treated patients (p 0.01). The frequency of positive sputum culture and the sensitivity and specificity of the pneumococcal urinary antigen test for diagnosing pneumococcal pneumonia were similar in the two groups. Patients with pre-hospital antibiotic treatment were less likely to present fever (p 0.02) or leucocytosis (p 0.001). Conversely, chest X-ray cavitation was more frequent in these patients (p 0.04). No significant differences were found in the frequency of patients classified into high-risk Pneumonia Severity Index classes, in intensive care unit admission, or in 30-day mortality between the groups. In conclusion, L. pneumophila occurrence was nearly three times higher in patients who received pre-hospital antibiotics. After a propensity-adjusted analysis, no significant differences were found in prognosis between study groups. Pre-hospital antibiotic use should be considered when choosing aetiological diagnostic tests and empirical antibiotic therapy in patients with CAP.

Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia.

The effects of antibiotic timing on outcomes of patients with community-acquired pneumonia (CAP) are controversial. Moreover, no information is available regarding this issue in healthcare-associated pneumonia (HCAP). We aimed to determine the impact of antibiotic timing on 30-day mortality of patients with CAP and HCAP. Non-immunocompromised adults admitted to hospital through the emergency department (ED) with community-onset pneumonia were prospectively observed from 2001 to 2009. Patients who received prior antibiotics were excluded. Of 1593 patients with pneumonia who were analyzed, 1274 had CAP and 319 HCAP. The mean time from patient arrival at the ED until antibiotic administration was 5.8 h (standard deviation (SD) 3.5) in CAP and 6.1 h (SD 3.8) in HCAP (p 0.30). Mortality was higher in patients with HCAP (5.5% vs. 13.5%; p <0.001). After adjusting for confounding factors in a logistic regression analysis, the antibiotic administration ≤4 h was not associated with decreased 30-day mortality in patients with CAP (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.57-2.21) and in patients with HCAP (OR 0.59, 95% CI 0.19-1.83). Similarly, antibiotic administration ≤8 h was not associated with decreased 30-day mortality in CAP (OR 1.58, 95% CI 0.64-3.88) and HCAP patients (OR 0.59, 95% CI 0.19-1.83). In conclusion, antibiotic administration within 4 or 8 h of arrival at the ED did not improve 30-day survival in hospitalized adults for CAP or HCAP.

Obstructive sleep apnoea and metabolic impairment in severe obesity.

Obstructive sleep apnoea (OSA) seems to worsen metabolism. This effect has not been evaluated in morbid obesity (MO). We hypothesised that the metabolic profile is more impaired in MO patients with OSA than in those without, and investigated whether any specific metabolic dysfunction is related to OSA in MO. A prospective multicentre cross-sectional study was conducted in consecutive subjects before bariatric surgery. OSA was defined as apnoea/hypopnoea index (AHI) ≥15 by overnight polysomnography. Anthropometrical, blood pressure (BP) and fasting blood measurements were obtained the morning after. Metabolic syndrome (MetS) was defined according to National Cholesterol Education Program Adult Treatment Panel III modified criteria. 159 patients were studied: 72% were female and 72% had OSA. MetS prevalence was 70% in OSA versus 36% in non-OSA (p<0.001). As AHI severity increased, metabolic parameters progressively worsened, even in those without type 2 diabetes (DM2). AHI was independently associated with systolic and diastolic BP, triglycerides and the percentage of glycosylated haemoglobin (HbA1c) in the total sample, and with systolic BP, high-density lipoprotein cholesterol and HbA1c in those samples without DM2. OSA increased the adjusted odds ratio of having MetS by 2.8 (95% CI 1.3-6.2; p=0.009). In MO, OSA is associated with major metabolic impairment caused by higher BP and poorer lipid and glucose control, independent of central obesity or DM2.

Low incidence of multidrug-resistant organisms in patients with healthcare-associated pneumonia requiring hospitalization.

Healthcare-associated pneumonia (HCAP) includes a broad spectrum of patients who acquire pneumonia through outpatient contact with the health system. Although limited prospective data exist, it has been suggested that all patients with HCAP should receive empirical therapy with a multidrug regimen directed against drug-resistant organisms. We aimed to determine the differences in aetiology and outcomes between HCAP groups and a community-acquired pneumonia (CAP) group, and to assess the presence of antibiotic-resistant bacteria. All consecutive non-immunocompromised adults hospitalized with pneumonia were prospectively included from 2001 to 2009. Patients who had had recent contact with the health system through nursing homes, home healthcare programmes, haemodialysis clinics or prior hospitalization were considered to have HCAP. A total of 2245 patients with pneumonia were hospitalized through the emergency room, of whom 577 (25.7%) had HCAP. Significant differences in causative pathogens were found between groups. Antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, resistant strains of Pseudomonas aeruginosa, and extended-spectrum ß-lactamase-producing Enterobacteriaceae, were scarce in all groups. In contrast, aspiration pneumonia was particularly frequent. No differences were found regarding inappropriate initial empirical antibiotic therapy between groups. Overall mortality was higher in patients who attended a hospital or haemodialysis clinic or received intravenous chemotherapy in the 30 days before pneumonia, and among patients who resided in a nursing home or long-term-care facility. In conclusion, most HCAP patients could be treated in the same way as patients with CAP, after carefully ruling out the presence of aspiration pneumonia.

Impact of antibiotic therapy on systemic cytokine expression in pneumococcal pneumonia.

The aim of this study was to compare the evolution of systemic cytokine levels over time in patients with pneumococal pneumonia treated either with ß-lactam monotherapy or with combination therapy (ß-lactam plus fluoroquinolone). Prospective observational study of hospitalized non-immunocompromised adults with PP. Concentrations of IL-6, IL-8, IL-10, and TNF-α were determined on days 0, 1, 2, 3, 5, and 7. Patients on ß-lactam monotherapy were compared with those receiving combination therapy. Fifty-two patients were enrolled in the study. Concentrations of IL-6, IL-8, and IL-10 decreased rapidly in the first days after admission, in accordance with the mean time to defervescence. High levels of IL-6 were found in patients with the worst outcomes, measured by the need for intensive care unit admission and mortality. No major differences in demographic or clinical characteristics or severity of disease were found between patients treated with ß-lactam monotherapy and those treated with combination therapy. IL-6 levels fell more rapidly in patients with combination therapy in the first 48 h (p = 0.016). Our data suggest that systemic expression of IL-6 production in patients with PP correlates with prognosis. Initial combination antibiotic therapy produces a faster decrease in this cytokine in the first 48 h.

Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes.

BACKGROUND: Host- and pathogen-related factors associated with septic shock in pneumococcal pneumonia are not well defined. The aim of this study was to identify risk factors for septic shock and to ascertain patient outcomes. Serotypes, genotypes and antibiotic resistance of isolated strains were also analysed. METHODS: Observational analysis of a prospective cohort of non-severely immunosuppressed hospitalised adults with pneumococcal pneumonia. Septic shock was defined as a systolic blood pressure of <90 mm Hg and peripheral hypoperfusion with the need for vasopressors for >4 h after fluid replacement. RESULTS: 1041 patients with pneumococcal pneumonia diagnosed by Gram stain and culture of appropriate samples and/or urine antigen test were documented, of whom 114 (10.9%) had septic shock at admission. After adjustment, independent risk factors for shock were current tobacco smoking (OR, 2.11; 95% CI, 1.02 to 4.34; p = 0.044), chronic corticosteroid treatment (OR, 4.45; 95% CI, 1.75 to 11.32; p = 0.002) and serotype 3 (OR, 2.24; 95% CI, 1.12 to 4.475; p = 0.022). No significant differences were found in genotypes and rates of antibiotic resistance. Compared with the remaining patients, patients with septic shock required mechanical ventilation more frequently (37% vs 4%; p<0.001) and had longer length of stay (11 vs 8 days; p<0.001). The early (10% vs 1%; p<0.001) and overall case fatality rates (25% vs 5%; p<0.001) were higher in patients with shock. CONCLUSIONS: Septic shock is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Current tobacco smoking, chronic corticosteroid treatment and infection caused by serotype 3 are independent risk factors for this complication.

Aetiology of, and risk factors for, recurrent community-acquired pneumonia.

Recurrent community-acquired pneumonia (CAP) requiring hospitalization is a matter of particular concern. However, current information on its prevalence, aetiology and risk factors is lacking. To address these issues, we performed an observational analysis of a prospective cohort of hospitalized adults with CAP. Recurrence was defined as two or more episodes of CAP 1 month apart within 3 years. Patients with severe immunosuppression or local predisposing factors were excluded. Of the 1556 patients, 146 (9.4%) had recurrent CAP. The most frequent causative organism was Streptococcus pneumoniae, both in patients with recurrent CAP and in those without recurrence. Haemophilus influenzae, other Gram-negative bacilli and aspiration pneumonia were more frequent among patients with recurrent CAP, whereas Legionella pneumophila was rarely identified in this group. Independent factors associated with recurrent CAP were greater age, lack of pneumococcal vaccination, chronic obstructive pulmonary disease (COPD) and corticosteroid therapy. In a sub-analysis of 389 episodes of pneumococcal pneumonia, the only independent risk factor for recurrence was lack of pneumococcal vaccination. Recurrence of CAP is not a rare clinical problem and it occurs mainly in the elderly, patients with COPD, and those receiving corticosteroids. Our study provides support for recommending pneumococcal vaccination for adults at risk of pneumonia, including those with a first episode of CAP.

Long-term relapses after 12-month treatment for Mycobacterium kansasii lung disease.

Long-lasting therapy for Mycobacterium kansasii lung disease with rifampin-containing multidrug regimens is needed to avoid relapses. The aim of the present study is to evaluate a short multidrug treatment regimen for M. kansasii lung disease. A retrospective observational study of 75 patients with M. kansasii lung disease was conducted in a teaching hospital from January 1990 to December 2005. In total, 75 (67.6%) out of 111 patients diagnosed with M. kansasii lung disease completed a 12-month multidrug treatment regimen, including rifampin, isoniazid and ethambutol, supplemented with streptomycin during the first 2-3 months. After a 41.5-month median follow-up, five (6.6%) patients relapsed. The relapse rate was 2.19 (95% confidence interval 0.71-5.12) per 100 person.yrs. Treatment compliance was considered to be appropriate in all five patients and no drug resistance developed in any case. In conclusion, a 12-month fixed-course treatment is effective in most cases of Mycobacterium kansasii lung disease, but may not be long enough for all patients.

Ingredientes funcionales en las fórmulas infantiles / Functional ingredients in the infant formulas

Los últimos avances realizados en la elaboración de las fórmulas infantiles responden al criterio de la ESPGHAN de acercarse al máximo a la composición de la leche materna y a la respuesta metabólica del lactante alimentado con leche materna. Entre los avances más significativos caben señalar los siguientes: Reducción del contenido de proteínas y fósforo (efecto bifidógeno): la conjunción del contenido reducido de proteínas y fósforo y la presencia de lactosa como hidrato de carbono mayoritario ha permitido conseguir que los lactantes alimentados con estas fórmulas infantiles tengan una flora predominante en bifidobacterias, similar a la de los alimentados con leche materna, con el consiguiente efecto positivo para el desarrollo del sistema inmunitario. Oligosacáridos: aunque se ha observado que una mezcla de dos oligosacáridos puede favorecer la flora bifidógena, la ESPGHAN señala que no se debe hacer una recomendación general sobre su utilización. Probióticos: entre las distintas cepas, se ha observado en ensayos clínicos que el Bifidobacterium lactis es efectivo en la prevención de diarreas y en el sistema inmunitario. Ácidos grasos poliinsaturados de cadena larga (LCPUFA’s): la adición de DHA y ARA con una relación 1/1potencia los efectos inmunomoduladores y permite conseguir unos niveles de DHA y ARA plasmáticos similares a los de los lactantes alimentados con leche materna. Nuceótidos: tienen un efecto positivo sobre la funcionalidad de los linfocitos intestinales y la inmunidad. Conclusión: es necesario efectuar ensayos clínicos aleatorizados a doble ciego placebo-controlado de cada una de las fórmulas funcionales (AU)

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Early mortality in patients with community-acquired pneumonia: causes and risk factors.

The first 48 h of evolution of patients with community-acquired pneumonia (CAP) are critical. The aim of the present study was to determine the frequency, causes and factors associated with early mortality in CAP. Nonimmunocompromised adults hospitalised with CAP were prospectively observed from 1995 to 2005. Early deaths, defined as death due to any cause < or = 48 h after admission, were compared with all patients who survived > 48 h. Furthermore, early deaths were compared with late deaths (patients who died > 48 h) and with survivors. Of 2,457 patients, 57 (2.3%) died < or = 48 h after admission. Overall mortality was 7.7%. The main causes of early mortality were respiratory failure and septic shock/multiorgan failure. Independent factors associated with early deaths were increased age, altered mental status at presentation, multilobar pneumonia, shock at admission, pneumococcal bacteraemia and discordant empiric antibiotic therapy. Currently, early mortality is relatively low and is caused by pneumonia-related factors. It occurs mainly among the elderly and in patients presenting with altered mental status, multilobar pneumonia and septic shock. Pneumococcal bacteraemia and discordant antibiotic therapy, mainly due to lack of coverage against Pseudomonas aeruginosa are also significant risk factors.