Mortality prediction using serum biomarkers and various clinical risk scales in community-acquired pneumonia

The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading. For example, serum concentrations of calcitonin precursors are increased in patients with infections. However, their predictive accuracy for the diagnosis of sepsis in unselected patients in a medical intensive care unit (ICU) is unknown. Therefore, we compared the usefulness of serum concentrations of calcitonin precursors, C-reactive protein, interleukin-6, and lactate for the diagnosis of sepsis in consecutive patients suffering from a broad range of diseases with an anticipated stay of > or =24 hrs in a medical ICU. Prospective cohort study. Medical intensive care unit in a university medical center. 101 consecutive critically ill patients. None. Blood samples were collected at various time points during the course of the disease. Systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock were diagnosed according to standardized criteria, and patients were reclassified daily without prior knowledge of the serum concentrations of calcitonin precursors or interleukin-6. At admission, 99% of the patients had systemic inflammatory response syndrome, 53% had sepsis, and 5% developed sepsis during their stay in the ICU. Calcitonin precursors, C-reactive protein, interleukin-6, and lactate levels increased with the severity of infection (p 1 ng/mL had sensitivity of 89% and specificity of 94% for the diagnosis of sepsis. High serum concentrations of calcitonin precursors were associated with poor prognosis (p = .01). In a medical ICU, serum calcitonin precursor concentrations are more sensitive and are specific markers of sepsis as compared with serum C-reactive protein, interleukin-6, and lactate levels.

International guidelines recommend a severity-based approach to management in community-acquired pneumonia. CURB65, CRB65 and the Pneumonia Severity Index (PSI) are the most widely recommended severity scores. The aim of this study was to compare the performance characteristics of these scores for predicting mortality in community-acquired pneumonia. A systematic review and meta-analysis was conducted according to MOOSE (meta-analysis of observational studies in epidemiology) guidelines. PUBMED and EMBASE were searched (1980-2009). 40 studies reporting prognostic information for the PSI, CURB65 and CRB65 severity scores were identified. Performance characteristics were pooled using a random effects model. Relationships between sensitivity and specificity were plotted using summary receiver operator characteristic (sROC) curves. All three scores predicted 30 day mortality. The PSI had the highest area under the sROC curve, 0.81 (SE 0.008), compared with CURB65, 0.80 (SE 0.008), p=0.1, and CRB65, 0.79 (0.01), p=0.09. These differences were not statistically significant. Performance characteristics were similar across comparable cut-offs for low, intermediate and high risk for each score. In identifying low risk patients, PSI (groups I and II) had the best negative likelihood ratio 0.08 (0.06-0.12) compared with CURB65 (score 0-1) 0.21 (0.15-0.30) and CRB65 (score 0), 0.15 (0.10-0.22). There were no significant differences in overall test performance between PSI, CURB65 and CRB65 for predicting mortality from community-acquired pneumonia.

C-reactive protein (CRP) is an acute phase protein synthesized by the liver primarily in response to interleukin-6. Initial studies have suggested that inflammatory markers may have a role in predicting severity. We investigated whether admission and day 4 CRP could predict severity in community-acquired pneumonia. A prospective study was carried out over a 2-year period in a large teaching hospital. CRP was measured on admission and on day 4. The outcomes of interest were: 30-day mortality; need for mechanical ventilation and/or inotropic support; development of complicated pneumonia (lung abscess, empyema, or complicated parapneumonic effusion); the value of predictive tests were assessed using multivariate logistic regression. There were 570 patients included in the study; 30-day mortality was 9.6%. Low CRP levels showed a high negative predictive value for excluding 30-day mortality (CRP <10 mg/L=100%, CRP <50=99.1%, CRP <100=98.9%, CRP <200=94.9%). Low admission CRP levels <100 mg/L were independently associated with reduced 30-day mortality (odds ratio [OR] 0.18; 0.04-0.85), P=.03; need for mechanical ventilation and/or inotropic support (OR 0.21; 0.14-0.4), P=.002; and complicated pneumonia (OR 0.05; 0.01-0.35), P=.003. A CRP that fails to fall by 50% or more within 4 days of admission is independently associated with increased 30 day mortality (OR 24.5; 6.4-93.4), P <.0001; need for mechanical ventilation and/or inotropic support (OR 7.1; 2.8-17.8), P <.0001 and complicated pneumonia (OR 15.4; 6.32-37.6), P <.0001. Admission CRP <100 mg/L has reduced risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia. Failure of CRP to fall by 50% or more at day 4 leads to an increased risk for 30-day mortality, need for mechanical ventilation and/or inotropic support, and complicated pneumonia. C-reactive protein is an independent marker of severity in community-acquired pneumonia.