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1.
PLoS One ; 13(1): e0191692, 2018.
Article in English | MEDLINE | ID: mdl-29360883

ABSTRACT

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2.


Subject(s)
Bacterial Proteins/administration & dosage , Immunity, Mucosal , Nanoparticles , Pneumonia, Bacterial/prevention & control , Adsorption , Animals , Bronchoalveolar Lavage Fluid , Enzyme-Linked Immunosorbent Assay , Female , Immunophenotyping , Mice , Mice, Inbred BALB C , Pneumonia, Bacterial/blood
2.
J Crit Care ; 42: 231-237, 2017 12.
Article in English | MEDLINE | ID: mdl-28797895

ABSTRACT

PURPOSE: Describe the patterns of C-reactive protein relative changes in response to antibiotic therapy in critically ill cancer patients with healthcare-associated pneumonia (HCAP) and its ability to predict outcome. METHODS: Secondary analysis of a prospective cohort of critically ill cancer patients with HCAP. CRP was sampled every other day from D0 to D6 of antibiotic therapy. Patients were classified according to an individual pattern of CRP-ratio response: fast - CRP at D4 of therapy was <0.4 of D0 CRP; slow - a continuous but slow decrease of CRP; non - CRP remained ≥0.8 of D0 CRP; biphasic - initial CRP decrease to levels <0.8 of the D0 CRP followed by a secondary rise ≥0.8. RESULTS: 129 patients were included and septic shock was present in 74% and invasive mechanical ventilation was used in 73%. Intensive care unit (ICU) and hospital mortality rates were 47% and 64%, respectively. By D4, both CRP and CRP-ratio of survivors were significantly lower than in nonsurvivors (p<0.001 and p=0.004, respectively). Both time-dependent analysis of CRP-ratio of the four previously defined patterns (p<0.001) as ICU mortality were consistently different [fast 12.9%, slow 43.2%, biphasic 66.7% and non 71.8% (p<0.001)]. CONCLUSION: CRP-ratio was useful in the early prediction of poor outcomes in cancer patients with HCAP.


Subject(s)
C-Reactive Protein/metabolism , Cross Infection/blood , Neoplasms/blood , Pneumonia, Bacterial/blood , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/metabolism , Critical Care , Critical Illness , Cross Infection/complications , Cross Infection/prevention & control , Female , Hospital Mortality , Humans , Intensive Care Units , Middle Aged , Neoplasms/complications , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/prevention & control , Prospective Studies , Respiration, Artificial/statistics & numerical data , Shock, Septic/blood , Shock, Septic/mortality
3.
Am J Med ; 127(10): 1010.e11-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24813862

ABSTRACT

BACKGROUND: Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort. METHODS: We analyzed adult patients with community-acquired pneumonia from a large multinational database (Community Acquired Pneumonia Organization) who were treated between 2001 and 2012 with more than 4 of the 6 prespecified clinical variables available. Association and discrimination were assessed using logistic regression analysis and area under the curve (AUC). RESULTS: Of 1939 included patients, the infectious cause was known in 594 (28.9%), including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%). The proposed clinical predictors fever, cough, hyponatremia, lactate dehydrogenase, C-reactive protein, and platelet count were all associated or tended to be associated with Legionella cause. A logistic regression analysis including all these predictors showed excellent discrimination with an AUC of 0.91 (95% confidence interval, 0.87-0.94). The original dichotomized score showed good discrimination (AUC, 0.73; 95% confidence interval, 0.65-0.81) and a high negative predictive value of 99% for patients with less than 2 parameters present. CONCLUSIONS: With the use of a large independent patient sample from an international database, this analysis validates previously proposed clinical variables to accurately rule out Legionella sp., which may help to optimize initial empiric therapy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/microbiology , Legionella pneumophila/isolation & purification , Pneumonia, Bacterial/microbiology , Aged , Aged, 80 and over , Algorithms , C-Reactive Protein/analysis , Community-Acquired Infections/blood , Community-Acquired Infections/drug therapy , Cough , Databases, Factual , Decision Making , Europe , Female , Humans , Hyponatremia/blood , L-Lactate Dehydrogenase/analysis , Legionella pneumophila/drug effects , Logistic Models , Male , Middle Aged , Multicenter Studies as Topic , North America , Platelet Count , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/drug therapy , Predictive Value of Tests , South America , Time Factors
4.
Rev Panam Salud Publica ; 29(6): 393-8, 2011 Jun.
Article in Spanish | MEDLINE | ID: mdl-21829961

ABSTRACT

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% 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.


Subject(s)
Bacteremia/epidemiology , Community-Acquired Infections/epidemiology , Inpatients/statistics & numerical data , Pneumonia, Bacterial/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Argentina/epidemiology , Bacteremia/blood , Case-Control Studies , Community-Acquired Infections/blood , Comorbidity , Female , Fever/epidemiology , Habits , Hemodynamics , Humans , Male , Middle Aged , Models, Biological , Pneumonia, Bacterial/blood , Predictive Value of Tests , Retrospective Studies , Risk Factors , Young Adult
5.
Respir Res ; 12: 104, 2011 Aug 05.
Article in English | MEDLINE | ID: mdl-21819560

ABSTRACT

BACKGROUND: ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF) in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1). METHODS: Mice were intratracheally instilled with the ExoU producing PA103 P. aeruginosa or its mutant with deletion of the exoU gene. After 24 h, animal bronchoalveolar lavage fluids (BALF) were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection. RESULTS: In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In in vitro assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively. CONCLUSION: ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during P. aeruginosa pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, in vitro detection of exoU gene in bacterial clinical isolates warrants investigation as a predictor of outcome of patients with P. aeruginosa pneumonia/sepsis and as a marker to guide treatment strategies.


Subject(s)
Bacterial Proteins/metabolism , Blood Coagulation , Fibrin/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Platelet Activating Factor/metabolism , Pneumonia, Bacterial/blood , Pseudomonas Infections/blood , Pseudomonas aeruginosa/metabolism , Pulmonary Alveoli/metabolism , Sepsis/blood , Animals , Bacterial Proteins/genetics , Bronchoalveolar Lavage Fluid/chemistry , Cell Line, Tumor , Disease Models, Animal , Epithelial Cells/metabolism , Epithelial Cells/microbiology , Female , Humans , Immunohistochemistry , Macrophages/metabolism , Macrophages/microbiology , Mice , Mutation , Plasminogen Activator Inhibitor 1/genetics , Pneumonia, Bacterial/genetics , Pneumonia, Bacterial/microbiology , Pseudomonas Infections/genetics , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/genetics , RNA, Messenger/metabolism , Respiratory Mucosa/metabolism , Respiratory Mucosa/microbiology , Sepsis/genetics , Sepsis/microbiology , Time Factors , Up-Regulation
6.
Rev. panam. salud pública ; 29(6): 393-398, June 2011. tab
Article in Spanish | LILACS | ID: lil-608268

ABSTRACT

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.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Bacteremia/epidemiology , Community-Acquired Infections/epidemiology , Inpatients/statistics & numerical data , Pneumonia, Bacterial/epidemiology , Argentina/epidemiology , Bacteremia/blood , Case-Control Studies , Community-Acquired Infections/blood , Comorbidity , Fever/epidemiology , Habits , Hemodynamics , Models, Biological , Pneumonia, Bacterial/blood , Predictive Value of Tests , Retrospective Studies , Risk Factors
7.
Rio de Janeiro; s.n; 2011. 109 p. ilus, graf.
Thesis in Portuguese | LILACS | ID: lil-619454

ABSTRACT

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...


Subject(s)
Humans , Animals , Male , Female , Mice , Blood Coagulation , Platelet Activating Factor/antagonists & inhibitors , Platelet Activating Factor/metabolism , Pseudomonas Infections/complications , Pseudomonas Infections/blood , Plasminogen Activator Inhibitor 1/blood , Bacterial Proteins/metabolism , Pseudomonas aeruginosa/metabolism , Pseudomonas aeruginosa/virology , Sepsis/blood , Platelet Activation , Pneumonia, Bacterial/blood , Sepsis/etiology
8.
J Infect ; 61(3): 205-11, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20600303

ABSTRACT

OBJECTIVES: The aim of this study was to examine the clinical usefulness of serial C-reactive protein (CRP) dosages in patients with nosocomial pneumonia (NP). METHODS: Prospective and observational study performed in a 24-beds Intensive Care Unit. Sixty four patients with NP, including non-ventilated patients and those with ventilator-associated pneumonia were included. Daily measurements of CRP were performed and CRP ratios were calculated from the day of antibiotic prescription (D0) until day 10. Patients were than classified according to the CRP ratios in 2 groups: 'good' response (CRP ratios lower than 0.67 at day 10) and 'poor' response (non-response or bi-phasic response). RESULTS: The poor response group (n = 34) had a mortality rate of 53% in comparison to 20% in the good response group (n = 30) (RR = 2.65; 95% CI, 1.21-5.79, p = 0.01). Significant differences between the two groups were found on CRP ratios at Day 4 (p = 0.01). The adequacy of antibiotic therapy was much lower in the group poor response in comparison to the group good response, 14% vs. 67% (p = 0.008), respectively. CONCLUSIONS: Daily CRP measurements in patients with nosocomial pneumonia may be useful in the identification of patients with poor outcome, as early as day 4, and detect patients with inappropriate antimicrobial therapy.


Subject(s)
C-Reactive Protein/analysis , Cross Infection/blood , Pneumonia, Bacterial/blood , Adult , Aged , Analysis of Variance , Cross Infection/drug therapy , Cross Infection/microbiology , Female , Humans , Male , Middle Aged , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Prospective Studies , Risk Factors , Treatment Outcome
9.
Scand J Infect Dis ; 42(9): 644-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20438288

ABSTRACT

Empirical antibiotic use is prescribed in managing children with pneumonia worldwide. We assessed the usefulness of procalcitonin (PCT) and interferon-alpha (IFN-alpha) in differentiating viral from bacterial pneumonia. Among 159 hospitalized children, pneumonia was diagnosed based on clinical complaints plus pulmonary infiltrate. Aetiology was investigated for 9 viruses and 4 atypical and 3 typical bacteria. PCT and IFN-alpha were measured in the serum sample collected on admission. Eight patients had bacteraemic infections, 38 had non-bacteraemic typical infections, and 19 patients had atypical bacterial infections. Viral and unknown aetiology was established in 57 (36%) and 34 (21%) cases, respectively. Three patients with bacterial infection without collected blood culture were excluded. IFN-alpha (IU/ml) was detectable in 20 (13%) cases. The difference among median PCT values of the bacteraemic (4.22; 1.56-7.56), non-bacteraemic typical bacterial (1.47; 0.24-4.07), atypical bacterial (0.18; 0.06-1.03) and only viral (0.65; 0.11-2.22) subgroups was significant (p = 0.02). PCT was > or =2 ng/ml in 52 (33%) cases. The presence of IFN-alpha was associated with PCT <2 ng/ml (90% vs. 64%, p = 0.02). The negative predictive value (95% confidence interval) of PCT > or =2 ng/ml was 95% (89-100%), 89% (78-100%), 93% (85-100%) for differentiation of bacteraemic from viral, atypical bacterial and non-bacteraemic typical bacterial infection, respectively, and 58% (49-68%) for differentiation between bacterial and viral infection. PCT may be useful in identifying bacteraemia among children hospitalized with community-acquired pneumonia. IFN-alpha was uncommonly detected.


Subject(s)
Bacteremia/diagnosis , Calcitonin/blood , Pneumonia, Bacterial/diagnosis , Pneumonia, Viral/diagnosis , Protein Precursors/blood , Bacteremia/blood , Calcitonin Gene-Related Peptide , Child, Preschool , Community-Acquired Infections/blood , Community-Acquired Infections/diagnosis , Community-Acquired Infections/microbiology , Diagnosis, Differential , Female , Humans , Infant , Infant, Newborn , Interferon-alpha/blood , Male , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/microbiology , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Predictive Value of Tests , Prospective Studies , ROC Curve , Reproducibility of Results , Statistics, Nonparametric
10.
Chest ; 134(5): 947-954, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18753464

ABSTRACT

BACKGROUND: High cortisol levels are frequent in patients with severe infections. However, the predictive value of total cortisol and of the presence of critical illness-related corticosteroid insufficiency (CIRCI) in severe community-acquired pneumonia (CAP) remains to be thoroughly evaluated. The aim of this study was to investigate the predictive value of adrenal response in patients with severe CAP admitted to the ICU. METHODS: Baseline and postcorticotropin cortisol levels C-reactive protein (CRP), d-dimer, clinical variables, sequential organ failure assessment (SOFA), APACHE (acute physiology and chronic health evaluation) II, and CURB-65 (confusion, urea nitrogen, respiratory rate, BP, age > or = 65 years) scores were measured in the first 24 h. Results are shown as median (interquartile range [IQR]). The major outcome measure was hospital mortality. RESULTS: Seventy-two patients with severe CAP admitted to the ICU were evaluated. Baseline cortisol levels were 18.1 microg/dL (IQR, 14.4 to 26.7 microg/dL), and the difference between baseline and postcorticotropin cortisol after 250 microg of corticotropin was 19 microg/dL (IQR, 12.8 to 27 microg/dL). Baseline cortisol levels presented positive correlations with scores of disease severity, including CURB-65, APACHE II, and SOFA (p < 0.05). Cortisol levels in nonsurvivors were higher than in survivors. CIRCI was diagnosed in 29 patients (40.8%). In univariate analysis, baseline cortisol, CURB-65, and APACHE II were predictors of death. The discriminative ability of baseline cortisol (area under receiver operating characteristic curve, 0.77; 95% confidence interval, 0.65 to 0.90; best cutoff for cortisol, 25.7 microg/dL) for in-hospital mortality was better than APACHE II, CURB-65, SOFA, d-dimer, or CRP. CONCLUSIONS: Baseline cortisol levels are better predictors of severity and outcome in severe CAP than postcorticotropin cortisol or routinely measured laboratory parameters or scores as APACHE II, SOFA, and CURB-65.


Subject(s)
Adrenal Glands/metabolism , Hydrocortisone/blood , Pneumonia, Bacterial/blood , Adrenocorticotropic Hormone/administration & dosage , Adrenocorticotropic Hormone/therapeutic use , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Community-Acquired Infections/blood , Community-Acquired Infections/drug therapy , Community-Acquired Infections/mortality , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Hormones/administration & dosage , Hormones/therapeutic use , Hospital Mortality , Humans , Male , Middle Aged , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/mortality , Prognosis , ROC Curve , Respiratory Care Units , Retrospective Studies , Severity of Illness Index
11.
Crit Care ; 10(5): R125, 2006.
Article in English | MEDLINE | ID: mdl-16956405

ABSTRACT

INTRODUCTION: This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated. METHODS: This prospective observational cohort study was conducted in a teaching hospital. The subjects were 75 patients consecutively admitted to the intensive care unit from October 2003 to August 2005 who developed VAP. Patients were followed for 28 days after the diagnosis, when they were considered survivors. Patients who died before the 28th day were non-survivors. There were no interventions. RESULTS: PCT, CRP and SOFA score were determined on day 0 and day 4. Variables included in the univariable logistic regression model for survival were age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, decreasing DeltaSOFA, decreasing DeltaPCT and decreasing DeltaCRP. Survival was directly related to decreasing DeltaPCT with odds ratio (OR) = 5.67 (95% confidence interval 1.78 to 18.03), decreasing DeltaCRP with OR = 3.78 (1.24 to 11.50), decreasing DeltaSOFA with OR = 3.08 (1.02 to 9.26) and APACHE II score with OR = 0.92 (0.86 to 0.99). In a multivariable logistic regression model for survival, only decreasing DeltaPCT with OR = 4.43 (1.08 to 18.18) and decreasing DeltaCRP with OR = 7.40 (1.58 to 34.73) remained significant. Decreasing DeltaCPIS was not related to survival (p = 0.59). There was a trend to correlate adequacy to survival. Fifty percent of the 20 patients treated with inadequate antibiotics and 65.5% of the 55 patients on adequate antibiotics survived (p = 0.29). CONCLUSION: Measurement of PCT and CRP at onset and on the fourth day of treatment can predict survival of VAP patients. A decrease in either one of these marker values predicts survival.


Subject(s)
C-Reactive Protein/antagonists & inhibitors , Calcitonin/antagonists & inhibitors , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/mortality , Protein Precursors/antagonists & inhibitors , Ventilators, Mechanical/microbiology , Adult , Aged , Aged, 80 and over , C-Reactive Protein/biosynthesis , Calcitonin/biosynthesis , Calcitonin/blood , Calcitonin Gene-Related Peptide , Cohort Studies , Humans , Middle Aged , Prospective Studies , Protein Precursors/biosynthesis , Protein Precursors/blood , Respiration, Artificial/mortality , Survival Rate
12.
Rev Med Inst Mex Seguro Soc ; 44(1): 5-11, 2006.
Article in Spanish | MEDLINE | ID: mdl-16497254

ABSTRACT

OBJECTIVE: To evaluate the role of docosahexaenoic acid (DHA) administered during the acute phase of pneumonia in infants, on appetite, cytokines and leptin concentrations. METHODS: Seventeen children between three months and 12 years of age were followed from hospitalization to discharge. Children were randomly assigned to receive DHA or placebo. The effect of treatment was evaluated on energy intake, cytokines, and leptin concentrations. RESULTS: Cytokine concentrations tended to decrease earlier in DHA children. By day 4, concentrations of IL-1beta and TNFalpha had decreased by 12%, while such concentrations increased by 12% and 250% in placebo children. Energy intake recovered in DHA children at discharge, but placebo children were still consuming only 60% of their requirements. CONCLUSIONS: Our results suggest that DHA administered in the acute phase of infection could modulate IL-1 and TNF production, and secondarily, decrease the effect of infection on appetite.


Subject(s)
Appetite/drug effects , Docosahexaenoic Acids/pharmacology , Pneumonia, Bacterial/drug therapy , Child , Child, Preschool , Female , Humans , Infant , Male , Pneumonia, Bacterial/blood
13.
Am J Clin Nutr ; 76(6): 1351-7, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12450903

ABSTRACT

BACKGROUND: The relative-dose-response (RDR) test is used to identify subjects with marginal liver vitamin A stores, but its use has not been evaluated during episodes of infection. OBJECTIVE: The objective was to assess, with the RDR test, the vitamin A status of children recovering from pneumonia. DESIGN: As part of a double-blind, placebo-controlled clinical trial of high-dose vitamin A supplements among children hospitalized with pneumonia in Lima, Peru, we examined the association of treatment group, nutritional status, severity of disease, and induction of the acute phase response [on the basis of serum C-reactive protein (CRP)] on serum retinol and the RDR test. RESULTS: Serum retinol was low at admission and increased significantly in both the vitamin A and placebo groups during recovery. Serum CRP had a significant, inverse association with retinol at both admission and discharge. Serum retinol and CRP concentrations never differed significantly between the treatment groups. Among subjects with CRP > or =10 mg/L, 21% in the vitamin A group and 20% in the placebo groups (P = 0.83) had a positive RDR test result. Among subjects with CRP <10 mg/L, 56% in the placebo group but only 6% in the vitamin A group had positive RDR test results (P = 0.002). CONCLUSION: The RDR test was useful in assessing the vitamin A status of children recovering from pneumonia when CRP concentrations were <10 mg/L but not when CRP concentrations were higher.


Subject(s)
Nutritional Status , Pneumonia, Bacterial/therapy , Pneumonia, Viral/therapy , Vitamin A/administration & dosage , Vitamin A/blood , Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/analysis , Child, Preschool , Dietary Supplements , Dose-Response Relationship, Drug , Double-Blind Method , False Positive Reactions , Female , Humans , Infant , Male , Peru , Placebos , Pneumonia, Bacterial/blood , Pneumonia, Viral/blood , Vitamin A Deficiency/diagnosis
14.
Rev Med Chil ; 130(9): 993-1000, 2002 Sep.
Article in Spanish | MEDLINE | ID: mdl-12434646

ABSTRACT

BACKGROUND: The clinical role of blood cultures (BC) in the management of hospitalized patients with community-acquired pneumonia (CAP) is controversial. AIM: To evaluate the clinical usefulness of blood cultures in CAP. MATERIAL AND METHODS: We prospectively studied 244 immunocompetent adults with two or more BC obtained at admission. The diagnostic yield of BC and its impact on antibiotic therapy were assessed. RESULTS: Mean age (mean +/- sd) of patients was 67 +/- 20 years, 80% had underlying diseases and 29% received antibiotics prior to admission. Hospital length of stay was 10.4 +/- 10 days and global mortality was 7%. The diagnostic yield of BC was only 8.2% (20 patients). Mortality was significantly higher in patients with positive BC (20%) than in those with negative BC (5.8%). In only one of the 20 patients with positive BC (0.4% of total study population), attending physicians changed empiric antimicrobial therapy based on these results. CONCLUSIONS: This study confirms that the diagnostic yield of BC in CAP hospitalized patients is low, that mortality in bacteremic patients is high and suggests that clinical usefulness of BC to guide changes on empiric antimicrobial therapy is limited, in part because attending physicians seldom use such information.


Subject(s)
Pneumonia, Bacterial/microbiology , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bacteremia/blood , Bacteremia/diagnosis , Bacteremia/drug therapy , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Female , Humans , Male , Middle Aged , Pneumonia, Bacterial/blood , Pneumonia, Bacterial/drug therapy , Prospective Studies
15.
Rev Med Chil ; 126(12): 1483-9, 1998 Dec.
Article in Spanish | MEDLINE | ID: mdl-10349163

ABSTRACT

BACKGROUND: The prevalence of Chlamydia pneumoniae infection varies according to the population and geographic area studied. AIM: To evaluate the incidence of Chlamydia pneumoniae infection in Chilean subjects with community acquired pneumonia. PATIENTS AND METHODS: Between 1995 and 1997, patients with community acquired pneumonia attending two emergency rooms in Santiago, were studied. The diagnosis of Chlamydia pneumoniae infection was based on the detection of Chlamydia pneumoniae specific IgG antibody in samples from both the acute and convalescent phase, using an indirect microimmunofluorescent technique. Evidence of present infection was defined as seroconversion, a significant increase in the titer of the second sample and an initial titer equal or greater than 1/512. RESULTS: During the study period, 160 patients consulted and seven (six male), aged 54 +/- 27 years old, complied with the diagnostic criteria of present Chlamydia pneumoniae infection. These patients had no special clinical or radiological features. Five of seven patients improved without any specific treatment. CONCLUSIONS: Eight percent of this sample of patients with community acquired pneumonia had Chlamydia pneumoniae infection. This agent should be included in the design of empiric treatment schemes, although our results cast doubt on the pathogenic role of Chlamydia pneumoniae in pneumonia.


Subject(s)
Chlamydia Infections/epidemiology , Chlamydophila pneumoniae , Pneumonia, Bacterial/epidemiology , Chile/epidemiology , Community-Acquired Infections/blood , Community-Acquired Infections/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Pneumonia, Bacterial/blood , Prospective Studies
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