Evaluación de predictores clínicos de bacteriemia en adultos hospitalizados por neumonía adquirida en la comunidad / Evaluation of clinical predictors of bacteremia in adults hospitalized for community-acquired pneumonia

OBJETIVO: Identificar elementos clínicos sencillos que hagan posible determinar adecuadamente los casos con mayor probabilidad de presentar aislamientos bacterianos en los hemocultivos. MÉTODOS: Estudio de casos y controles con pacientes internados por neumonía adquirida en la comunidad entre 1998 y 2009, definiéndose como casos a los pacientes que presentaron hemocultivos positivos y como controles a aquellos con hemocultivos negativos. Se registraron variables demográficas y clínicas y se las sometió a un análisis bivariado. Las que presentaron diferencias estadísticamente significativas entre los grupos fueron introducidas en un modelo de regresión logística para definir predictores independientes y generar un modelo de predicción clínica. RESULTADOS: De los 322 pacientes estudiados, 15,2 por ciento tuvo hemocultivos positivos. Diez variables mostraron diferencias significativas, pero solo tres (temperatura <38°C, sodio <135 mEq/L y puntaje CURB-65) fueron seleccionadas para el análisis multivariado. El modelo desarrollado mostró escasa capacidad para predecir el resultado de los hemocultivos (R² = 0,176; Hosmer-Lemeshow: P = 0,338). CONCLUSIONES: Los datos obtenidos en esta serie no evidenciaron elementos clínicos con capacidad suficiente para predecir el resultado de los hemocultivos.

OBJECTIVE: Identify simple clinical elements that can be used to adequately determine the cases with the highest probability of presenting bacterial isolates in blood cultures. METHODS: Case-control study with patients hospitalized for community-acquired pneumonia from 1998-2009. Patients with positive blood cultures were defined as cases, and patients with negative blood cultures were defined as controls. The demographic and clinical variables were recorded and a bivariate analysis was conducted. The variables with statistically significant differences between the groups were introduced in a logistic regression model in order to define the independent predictors and generate a clinical prediction model. RESULTS: A total of 15.2 percent of the 322 patients studied had positive blood cultures. Ten variables showed significant differences, but only three variables (temperature <38°C, sodium <135 mEq/L and CURB-65 score) were selected for the multivariate analysis. The model developed showed limited capacity to predict the result of the blood cultures (R² = 0.176; Hosmer-Lemeshow: P = 0.338). CONCLUSIONS: The data obtained in this series did not demonstrate clinical elements with sufficient capacity to predict the result of the blood cultures.

Atividade pró-trombótica da toxina ExoU de Pseudomonas aeruginosa detectada em modelos experimentais in vivo e in vitro / Prothrombotic activity of the Pseudomonas aeruginosa toxin ExoU detected in experimental models in vivo and in vitro

Pseudomonas aeruginosa é um importante agente de pneumonia, particularmente em pacientes submetidos à ventilação mecânica, que pode evoluir para sepse, com elevadas taxas de letalidade. Na sepse, o processo inflamatório sistêmico exacerbado favorece o desequilíbrio entre as vias de coagulação e fibrinólise e a instalação de um estado pró-coagulante, com o aparecimento de trombose microvascular, coagulação intravascular disseminada e falência de múltiplos órgãos. Conhecendo a potente atividade pró-inflamatória da toxina ExoU produzida por P. aeruginosa, decorrente de sua atividade fosfolipásica A2, o objetivo desta tese foi investigar seu potencial de indução de alterações hemostáticas relacionadas à patogênese da sepse. Utilizando modelo de sepse em camundongos inoculados, por via intratraqueal, com suspensões de P. aeruginosa produtora de ExoU (PA103) ou de cepa com deleção do gene exoU, não produtora da toxina, foi mostrado que ExoU determinou maior gravidade da infecção, maior taxa de letalidade, leucopenia, trombocitose, hiperpermeabilidade vascular e transudação plasmática, evidenciadas, respectivamente, pela maior concentração de proteínas nos lavados broncoalveolares (LBAs) e acúmulo do corante Azul de Evans, previamente inoculado nos animais, por via endovenosa, no parênquima renal. ExoU favoreceu, também, a ativação plaquetária, confirmada pela maior concentração de plaquetas expressando P-seletina em sua supefície, maior número de micropartículas derivadas de plaquetas e maior concentração plasmática de tromboxano A2. A histopatologia dos pulmões e rins dos animais infectados com PA103 confirmou a formação de microtrombos, que não foram detectados nos animais controles ou infectados com a cepa mutante. Nos pulmões, a produção de ExoU determinou intensa resposta inflamatória com maior concentração de leucócitos totais e polimorfonucleados, interleucina-6 e fator de necrose tumoral-alfa nos LBAs. A análise imunohistoquímica mostrou intensa deposição...

Pseudomonas aeruginosa is an important agent of pneumonia, mainly in patients undergoing mechanical ventilation, which can progress to sepsis with high mortality rates. In sepsis, the systemic inflammatory process favors exacerbated imbalance between the coagulation and fibrinolysis pathways and the installation of a procoagulant state, leading to microvascular thrombosis, disseminated intravascular coagulation and multiple organ failure. Knowing the powerful proinflammatory activity of the P. aeruginosa toxin ExoU, secondary to its phospholipase A2 activity, the goal of this study was to investigate the ExoU potential to induce hemostatic changes related to sepsis pathogenesis. By using a murine model of pneumosepsis, obtained by the intratracheal injection of suspensions of the ExoU-producing PA103 P. aeruginosa strain or of its isogenic mutant PA103 exoU, defective in the toxin synthesis, ExoU was shown to enhance the severity of the infection and to induce higher mice mortality rate as well as leukopenia, thrombocytosis, vascular hyperpermeability and plasma transudation, evidenced, respectively, by the higher protein concentration in the bronchoalveolar lavage fluids (BALF) and accumulation of Evans blue dye, previously intravenous infectioned, in mice renal parenchyma. ExoU also favored platelet activation, evidenced by the higher concentration of platelets expressing P-selectin on their surface, greater number of platelet-derived microparticles and increased plasma concentration of thromboxane A2. Histopathology of the lungs and kidneys of PA103 - infected animals confirmed the formation of microthrombi, which were not detected in controls or in animals infected with the bacterial mutant. In lungs, ExoU induced an intense inflammatory response with high concentrations of total and polymorphonuclear leukocytes, interleukin-6 and tumor necrosis factor-alfa in mice BALF. Immunohistochemical analysis showed intense fibrin deposition in the alveoli...

Sero diagnosis of Legionella infection in community acquired pneumonia.

Background & objectives: Legionella pneumophila has been increasingly recognized as an emerging pathogen responsible for community acquired pneumonia (CAP) worldwide. In India, the actual burden is not known. The present study was thus undertaken to see the presence of Legionella infection in patients with community acquired pneumonia admitted in a tertiary care centre in north India. Methods: Both children and adults (n=113) with symptoms of pneumonia were included in the study. Clinical samples (blood, urine, nasopharyngeal aspirates, bronchoalveolar lavage, sputum, etc.) were collected and subjected to culture and other tests. Enzyme linked immunosorbent assay (ELISA) was done by commercial kits for all the three classes of immunoglobulins (IgG, IgM & IgA). Urinary antigen was also detected using commercial kits. Culture was performed on 51 respiratory tract fluid samples. Serum samples of 44 healthy controls were also screened for the presence of anti-legionella antibodies (IgG, IgM & IgA). Results: Thirty one of the 113 cases (27.43%) were serologically positive. Anti-legionella IgG, IgM and IgA antibodies were positive in 7.96, 15.92 and 11.50 per cent patients respectively. In controls, seropositivity was 9.09 (4/44). IgA was positive in 3 and IgM, IgG combined in one. Antigenuria detection by Microwell ELISA kit showed 17.69 per cent positivity. Four antigenuria positive patients were also serologically positive; of these two patients were positive for IgM, hence considered as confirmed cases of Legionella infection. None of the sample was culture positive. Interpretation & conclusions: Combination of serology and antigenuria detection may be a valuable tool for the diagnosis of Legionella infection in absence of culture positivity. In order to evaluate the actual burden of Legionella in community acquired pneumonia, further studies with larger samples need to be done.

Role of C-Reactive Protein and Procalcitonin in Differentiation of Tuberculosis from Bacterial Community Acquired Pneumonia

BACKGROUND/AIMS: We investigated the utility of serum C-reactive protein (CRP) and procalcitonin (PCT) for differentiating pulmonary tuberculosis (TB) from bacterial community-acquired pneumonia (CAP) in South Korea, a country with an intermediate TB burden. METHODS: We conducted a prospective study, enrolling 87 participants with suspected CAP in a community-based referral hospital. A clinical assessment was performed before treatment, and serum CRP and PCT were measured. The test results were compared to the final diagnoses. RESULTS: Of the 87 patients, 57 had bacterial CAP and 30 had pulmonary TB. The median CRP concentration was 14.58 mg/dL (range, 0.30 to 36.61) in patients with bacterial CAP and 5.27 mg/dL (range, 0.24 to 13.22) in those with pulmonary TB (p<0.001). The median PCT level was 0.514 ng/mL (range, 0.01 to 27.75) with bacterial CAP and 0.029 ng/mL (range, 0.01 to 0.87) with pulmonary TB (p<0.001). No difference was detected in the discriminative values of CRP and PCT (p=0.733). CONCLUSIONS: The concentrations of CRP and PCT differed significantly in patients with pulmonary TB and bacterial CAP. The high sensitivity and negative predictive value for differentiating pulmonary TB from bacterial CAP suggest a supplementary role of CRP and PCT in the diagnostic exclusion of pulmonary TB from bacterial CAP in areas with an intermediate prevalence of pulmonary TB.

Clinical Investigation of Cavitary Tuberculosis and Tuberculous Pneumonia

BACKGROUND: The radiographic characteristics of tuberculous pneumonia in adults are similar to primary tuberculosis that occurs in childhood, and upper lobe cavitary tuberculosis is the hallmark of postprimary tuberculosis. The purpose of this study was to investigate the factors associated with tuberculous pneumonia by making comparison with cavitary tuberculosis. METHODS: The medical records and radiographic findings of patients with cavitary tuberculosis and tuberculous pneumonia, and who were diagnosed between March 2003 and February 2006, were analyzed retrospectively. RESULTS: Forty patients had cavitary tuberculosis and sixteen patients had tuberculous pneumonia. Fever was more frequent for tuberculous pneumonia, whereas hemoptysis was more frequent for cavitary tuberculosis. The duration of symptoms before visiting the hospital was shorter, but the diagnosis after admission was more delayed for tuberculous pneumonia patients than for cavitary tuberculosis patients. The prevalence of underlying comorbidities such cancer, diabetes, alcoholism and long-term steroid use was not different between the two groups. The patients with tuberculous pneumonia were older and they had lower levels of serum albumin and hemoglobin than those with cavitary tuberculosis. The patients with tuberculous pneumonia showed a tendency to have more frequent endobronchial lesion. Tuberculous pneumonia occurred in any lobe, whereas the majority of cavitary tuberculosis patients had upper lung lesion, but the prevalence of lymphadenopathy, pleural effusion and previous tuberculosis scar was not different between the two groups. CONCLUSIONS: Older age, a lower level of serum albumin and hemoglobin and a random distribution of lesion were associated with tuberculosis pneumonia as compared with cavitary tuberculosis. These findings suggest that the pathogenesis of tuberculous pneumonia might be different from that of cavitary tuberculosis.

Atypical Pathogens as Etiologic Agents in Hospitalized Patients with Community-Acquired Pneumonia in Korea: A Prospective Multi-Center Study

Local epidemiologic data on the etiologies of patients hospitalized with community-acquired pneumonia (CAP) is needed to develop guidelines for clinical practice. This study was conducted prospectively to determine the proportion of atypical bacterial pathogens in adults patients hospitalized with CAP in Korea between October 2001 and December 2002. Microbiological diagnosis was determined by serology for antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneu-mophila. Nucleic acid of M. pneumoniae and C. pneumoniae in respiratory samples and Legionella antigen in urine samples were detected. The study population consisted of 126 patients (71 males, 55 females), averaging 54.6 yr (SD+/-17.8), whose paired sera were available. An etiologic diagnosis for atypical pathogens was made in 18 patients (14.3%): C. pneumoniae 9 (7.1%), M. pneumoniae 8 (6.3%), and L. pneumophila 3 patients (2.4%). Streptococcus preumoniae and other typical pathogens were isolated from 36 patients (28.6%). Of 126 patients, 16 (12.7%) were admitted to intensive care unit and atypical pathogens were identified in 5 patients (31.3%). Initial clinical features of patients with pneumonia due to atypical, typical or undetermined pathogens were indistinguishable. We conclude that atypical pathogens should be seriously considered in hospitalized patients with CAP, when initiating empiric treatment in Korea.

Serum Vascular Endothelial Growth Factor in Pediatric Patients with Community-Acquired Pneumonia and Pleural Effusion

This study investigated the serum vascular endothelial growth factor (VEGF) levels in children with community-acquired pneumonia. Serum VEGF levels were measured in patients with pneumonia (n=29) and in control subjects (n=27) by a sandwich enzyme-linked immunosorbent assay. The pneumonia group was classified into bronchopneumonia with pleural effusion (n=1), bronchopneumonia without pleural effusion (n=15), lobar pneumonia with pleural effusion (n=4), and lobar pneumonia without pleural effusion (n=9) groups based on the findings of chest radiographs. We also measured serum IL-6 levels and the other acute inflammatory parameters. Serum levels of VEGF in children with pneumonia were significantly higher than those in control subjects (p<0.01). Children with lobar pneumonia with or without effusion showed significantly higher levels of serum VEGF than children with bronchopneumonia. For lobar pneumonia, children with pleural effusion showed higher levels of VEGF than those without pleural effusion. Children with a positive urinary S. pneumonia antigen test also showed higher levels of VEGF than those with a negative result. Serum IL-6 levels did not show significant differences between children with pneumonia and control subjects. Serum levels of VEGF showed a positive correlation with the erythrocyte sedimentation rate in the children with pneumonia. In conclusion, VEGF may be one of the key mediators that lead to lobar pneumonia and parapneumonic effusion.

Circulating interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha in children with febrile infection--a comparison with C-reactive protein.

Circulating interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were examined in 42 febrile children with fever lasting more than 4 days. Their diagnosis were probable viral syndrome in 22, urinary tract infection (UTI) in 10, and probable bacterial pneumonia in 10. None of our study patients had detectable serum IL-1 beta. TNF-alpha levels were significantly higher in children with pneumonia than in those with viral syndrome (p < 0.01). Children with UTI and pneumonia had significantly higher IL-6 and CRP, compared to those with probable viral syndrome (p < 0.01 for both IL-6 and CRP). When appropriate cutoff values are chosen, IL-6 had greatly improved specificity (86.4%, > 20 pg/ml) to demonstrate UTI and pneumonia, as compared to that using CRP (48%, > 40 mg/l). After three days' antibiotic treatment, IL-6 fell to control levels in children with UTI and pneumonia, while CRP remained elevated. There was no difference in TNF-alpha values before and after treatment. Thus, IL-6, rather than IL-1 beta and TNF-alpha, may be a helpful diagnostic tool for evaluation of pediatric febrile infection. Sequential studies involving more patients are needed to determine whether IL-6 is better than CRP in this clinical setting.