Short- and long-term mortality in patients with community-acquired severe sepsis and septic shock.

BACKGROUND: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population-based reference cohort. METHODS: Two hundred and twelve patients who, within the first 24 h after arrival at the hospital, presented with infection and had failure of at least 1 organ system were included. A population-based reference group of 79,857 patients was identified, and data on comorbidities were extracted from the National Danish Patient Registry. We analyzed the hazard ratio for mortality at predefined intervals. RESULTS: Absolute mortality within the first 30 days was 69/211 (33%, 95% confidence interval (CI) 25-41%), with a cumulative mortality of 121/211 (57%, 95% CI 48-69%) for the entire follow-up. Among septic patients who survived the first 30 days, the mortality hazard ratio was 2.7 (95% CI 1.7-4.3) until day 365, and among septic patients who survived the first year, the 1-4 y mortality hazard ratio was 2.3 (95% CI 1.7-3.3), compared to the community-based reference persons (multivariate Cox regression controlling for age, sex, and Charlson comorbidity index). CONCLUSIONS: Patients with severe sepsis and septic shock who survived the first 30 days had a 2.7 times higher mortality hazard in the first year and a 2.3 times higher mortality hazard in the next 3 y, compared to persons of similar age, sex, and comorbidity level.

Aetiology and prediction of pneumonia in lower respiratory tract infection in primary care.

BACKGROUND: Knowledge of predominant pathogens and their association with outcome are of importance for the management of lower respiratory tract infection (LRTI). As antibiotic therapy is indicated in pneumonia and not in acute bronchitis, a predictor of pneumonia is needed. AIM: To describe the aetiology and outcome of LRTI in adults with pneumonic and adults with non-pneumonic LRTI treated in general practice and to identify predictors of radiographic pneumonia. DESIGN OF STUDY: Prospective, observational study. SETTING: Forty-two general practices and an outpatient clinic at the Department of Infectious Diseases, Odense University Hospital, Denmark. METHOD: A total of 364 adults diagnosed with community-acquired LRTI by their GP were studied with chest radiography, vital signs, biochemical markers of inflammation (C-reactive protein [CRP] and leukocyte count), and microbiological examinations. Primary outcome measure was hospitalisation within 4 weeks. RESULTS: Pneumonia was radiographically verified in 48 of 364 patients (13%). Bacterial infection was seen more often in patients with pneumonia (33% versus 17%, P<0.001), and viral infection more often in non-pneumonic patients (26% versus 13%, P<0.05). Hospitalisation was more common in patients with pneumonia compared to non-pneumonic patients (19 versus 3%, P<0.001); and in patients with pneumococcal infection compared with patients without pneumococcal infection (26 versus 4%, P = 0.001). The positive predictive value of GPs' diagnosis of pneumonia was low (0.23), but the vital signs, CRP, and leukocyte count had comparably low positive predictive values (0.23-0.30). CONCLUSION: Streptococcus pneumoniae was the most common bacterial pathogen. The risk of hospitalisation was highest among patients with pneumonia or pneumococcal infection; this emphasises the importance of coverage of S. pneumoniae when treatment is indicated. CRP should not be introduced for diagnosis of radiographic pneumonia in general practice before its use has been investigated in prospective, controlled intervention trials using CRP-guided treatment algorithms.

Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care.

BACKGROUND: The role of procalcitonin in diagnosing bacterial infection has mainly been studied in patients with severe infections. There is no study on the value of procalcitonin measurements in adults with lower respiratory tract infection (LRTI) treated in primary care. AIM: To evaluate the accuracy of plasma procalcitonin in predicting radiographic pneumonia, bacterial infection, and adverse outcome in a population of adults with LRTI treated in primary care. DESIGN OF STUDY: Prospective, observational study. SETTING: Forty-two general practices and an outpatient clinic at the Department of Infectious Diseases, Odense University Hospital, Denmark. METHOD: A total of 364 patients with LRTI were prospectively enrolled from 42 general practices. Patients were examined with chest radiography, microbiological analyses, and measurements of C-reactive protein (CRP) and procalcitonin. The outcome measure was hospitalisation within 4 weeks of enrollment. RESULTS: Median procalcitonin was 0.05 ng/ml, which was below the functional sensitivity of the assay (0.06 ng/ml). In predicting radiographic pneumonia, bacterial infection, and hospitalisation, the sensitivities of procalcitonin >0.06 ng/ml were 0.70, 0.51, and 0.67, and of CRP were > or =20 mg/l, 0.73, 0.56, and 0.74 respectively. Corresponding positive predictive values were between 0.09 and 0.28. CONCLUSION: Both procalcitonin >0.06 ng/ml and CRP > or =20 mg/l were associated with radiographic pneumonia, bacterial infection, and subsequent hospitalisation, but positive predictive values were too low for any of the two inflammatory markers to be of use in clinical practice. To measure procalcitonin values accurately in the primary care setting, a more sensitive method is needed, but there was no indication that procalcitonin is superior to CRP in identifying patients with pneumonia, bacterial aetiology, or adverse outcome.

A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study.

INTRODUCTION: High-mobility group box-1 protein (HMGB1) has been known as a chromosomal protein for many years. HMGB1 has recently been shown to be a proinflammatory cytokine with a role in the immunopathogenesis of sepsis. Lipopolysaccharide-binding protein (LBP) has a central role in the innate immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included analysis of the levels of the inflammatory markers in relation to the severity of infection, to the prognosis and to the ability to identify patients with bacteraemia. METHODS: Patients suspected of having severe infections and admitted to a department of internal medicine were included in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score and mortality on day 28 were recorded. Plasma and serum were sampled within 24 hours after admission. Levels of all studied markers (HMGB1, LBP, PCT, IL-6, C-reactive protein, white blood cell count and neutrophils) were measured with commercially available laboratory techniques. RESULTS: A total of 185 adult patients were included in the study; 154 patients fulfilled our definition of infection. Levels of HMGB1, LBP and PCT were higher in infected patients compared with a healthy control group (P < 0.0001). Levels of HMGB1, LBP and PCT were higher in the severe sepsis group compared with the sepsis group (P < 0.01). No differences were observed in levels of the inflammatory markers in fatal cases compared with survivors. Levels of all studied markers were higher in bacteraemic patients compared with nonbacteraemic patients (P < 0.05). PCT performed best in a receiver-operator curve analysis discriminating between bacteraemic and nonbacteraemic patients (P < 0.05). HMGB1 correlated to LBP, IL-6, C-reactive protein, white blood cell count and neutrophils (P < 0.001). LBP correlated to PCT, IL-6 and C-reactive protein (P < 0.001). CONCLUSION: Levels of HMGB1, PCT and LBP were higher in infected patients compared with those in healthy controls, and levels were higher in severe sepsis patients compared with those in sepsis patients. Levels of all studied inflammatory markers (HMGB1, LBP, PCT, IL-6) and infection markers (C-reactive protein, white blood cell count, neutrophils) were elevated among bacteraemic patients. PCT performed best as a diagnostic test marker for bacteraemia.

Soluble haemoglobin scavenger receptor (sCD163) in patients with suspected community-acquired infections.

The aim of our study was to evaluate soluble haemoglobin scavenger receptor (sCD163) as a molecular marker in patients with community-acquired infections. One hundred and ninety-four adult patients admitted to the Department of Internal Medicine, Odense University Hospital, with suspected community-acquired infection were included in a prospective study. Plasma and serum were sampled from all patients on day of admission and sCD163 and interleukin-6 levels were measured. Demographic data, co-morbidity, microbiological aetiology, biochemical parameters, focus of infection, severity score and mortality on day 28 were recorded. Median age was 68 (range 18-92) years. Mortality rate among infected patients on day 28 was 3.8%. sCD163 concentrations (median and range) were: 2.99 mg/l (1.22-12.65) in non-infected patients, 3.62 mg/l (1.59-74.04) (p=0.08) in infected patients without systemic inflammatory response syndrome, 3.2 mg/l (0.54-22.51) (p=0.4) in patients with sepsis, 3.63 mg/l (1.71-28.4) (p=0.01) in patients with severe sepsis, and 4.9 mg/l (2.66-28.4) (p=0.003) in patients with bacteraemia. In this cohort dominated by mild infections, a moderate elevation of sCD163 was observed only in patients with severe sepsis and/or bacteraemia. sCD163 did not discriminate between infected and non-infected patients.

Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease.

YKL40 is secreted by activated macrophages and neutrophils. Elevated serum concentrations of YKL40 are found in patients with diseases characterized by inflammation or ongoing fibrosis. The aim of this study was to evaluate serum YKL-40 levels in patients with Streptococcus pneumoniae bacteremia and to correlate these levels with clinical findings and outcomes. YKL40 was determined by ELISA and 89 patients were included in the study. Serum YKL-40 levels were significantly higher in patients with S. pneumoniae bacteremia (median 342 microg/l; range 20-20,400 microg/l) than in age-matched healthy subjects (44 microg/l; 20-184; p < 0.001). Serum YKL-40 levels were related to the severity of the infection, with significantly higher serum YKL-40 levels being observed in patients who needed hemodialysis (p < 0.001), pharmacological treatment of hypotension (p < 0.001) and mechanical ventilation (p = 0.003) compared to those in patients who did not need this supportive treatment. Nineteen patients died and these patients had significantly higher serum YKL-40 levels (980 microg/l; 88-20,400 microg/l) than those of survivors (256 microg/l; 20-9,100 microg/l; p < 0.001). Serum YKL40 level was an independent prognostic factor of survival in logistic multivariate regression analysis (p = 0.002). In conclusion, high serum levels of YKL40 indicated a poorer prognosis for patients with S. pneumoniae bacteremia.

Variant mannose-binding lectin alleles are not associated with susceptibility to or outcome of invasive pneumococcal infection in randomly included patients.

Invasive pneumococcal disease is a serious infection that primarily affects very young children and elderly or immunocompromised individuals but also affects previously healthy people. Variant mannose-binding lectin (MBL) alleles are associated with recurrent infections and may be a risk factor for pneumococcal infections. To assess the influence of MBL genotypes on the course and outcome of invasive pneumococcal disease, clinical data for 141 adult patients were collected prospectively and their genotypes were determined. All patients included had positive blood cultures for Streptococcus pneumoniae. The distribution of variant MBL alleles related to low MBL serum concentrations was similar among the patients and healthy individuals, and MBL genotype was not associated with infection outcome. Thus, in a random adult population with invasive pneumococcal infection, MBL does not seem to play a role in the pathophysiology, in contrast to earlier observations in patients with other concomitant immune abnormalities.