Reetta Huttunen

Plasma level of soluble urokinase-type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study.

Huttunen R, Syrjänen J, Vuento R, Hurme M, Huhtala H, Laine J, Pessi T, Aittoniemi J (Tampere University Hospital; University of Tampere Medical School, University of Tampere; Centre for Laboratory Medicine, Pirkanmaa Hospital District; University of Tampere Medical School; School of Health Sciences, University of Tampere; and Medical School, University of Tampere; Tampere, Finland) Plasma level of soluble urokinase‐type plasminogen activator receptor as a predictor of disease severity and case fatality in patients with bacteraemia: a prospective cohort study. J Intern Med 2011; 270: 32–40.

Smoking and the outcome of infection

Abstract.  Huttunen R, Heikkinen T, Syrjänen J. (Department of Internal Medicine, Tampere University Hospital, Tampere; Department of Pediatrics, Turku University Hospital, Turku; Finland) Smoking and the Outcome of Infection (Review). J Intern Med 2010; 269: 258–269.

Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia

BackgroundBacteraemia is still a major cause of case fatality in all age groups. Our aim was to identify the major underlying conditions constituting risk factors for case fatality in bacteraemia patients.MethodsThe study involved 149 patients (79 male and 70 female) with bacteraemia caused by Staphylococcus aureus (S. aureus) (41 patients), Streptococcus pneumoniae (Str. pneumoniae) (42 patients), β-hemolytic streptococcae (β-hml str.) (23 patients) and Eschericia coli (E. coli) (43 patients). Underlying diseases, alcohol and tobacco consumption and body mass index (BMI) were registered. Laboratory findings and clinical data were registered on admission and 6 consecutive days and on day 10–14. Case fatality was studied within 30 days after positive blood culture. Associations between underlying conditions and case fatality were studied in univariate analysis and in a multivariate model.ResultsNineteen patients (12.8%) died of bacteraemia. We found obesity (p = 0.002, RR 9.8; 95% CI 2.3 to 41.3), smoking (p < 0.001, RR 16.9; 95% CI 2.1 to 133.5), alcohol abuse (p = 0.008, RR 3.9; 95% CI 1.3 to 11.28), COPD (p = 0.01, RR 8.4; 95% CI 1.9 to 37.1) and rheumatoid arthritis (p = 0.045, RR 5.9; 95% CI 1.2 to 28.8) to be significantly associated with case fatality in bacteraemia in univariate model. The median BMI was significantly higher among those who died compared to survivors (33 vs. 26, p = 0.003). Obesity and smoking also remained independent risk factors for case fatality when their effect was studied together in a multivariate model adjusted with the effect of alcohol abuse, age (continuos variable), sex and causative organism.ConclusionOur results indicate that obesity and smoking are prominent risk factors for case fatality in bacteraemic patients. Identification of risk factors underlying fatal outcome in bacteraemia may allow targeting of preventive efforts to individuals likely to derive greatest potential benefit.

High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients.

Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan (trp) catabolism, may play a critical role in various inflammatory disorders. Recent studies on trauma patients have suggested that the degradation of trp is associated with the development of sepsis. The role of IDO activity in bacteremic patients is unclear. We studied IDO activity in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, &bgr;-hemolytic streptococcae, or Eschericia coli. The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood culture and on recovery. The kyn-to-trp ratio (kyn/trp), reflecting the activity of the IDO enzyme, was calculated. The maximum value in the ratio for every patient during 1 to 4 days after positive blood culture was used in analysis. The maximum kyn/trp ratio was significantly higher in nonsurvivors versus those who survived (193.7 vs. 82.4 &mgr;mol/mmol; P = 0.001). The AUCROC of maximal kyn/trp in the prediction of case fatality was 0.75 (95% confidence interval, 0.64-0.87), and the kyn/trp ratio at a cutoff level of 120 &mgr;mol/mmol showed 83% sensitivity and 69% specificity for fatal disease. A kyn/trp ratio greater than 120 &mgr;mol/mmol was associated with increased risk of death versus low (≤120 &mgr;mol/mmol) ratios (odds ratio, 10.8; confidence interval, 3.0-39.8). High IDO activity also remained an independent risk factor for case fatality in a multivariate model adjusted for potential confounders. The data in this report demonstrate that IDO activity is markedly increased in bacteremia patients, constituting an independent predictor of severe disease and case fatality.

Fatal Outcome in Bacteremia is Characterized by High Plasma Cell Free DNA Concentration and Apoptotic DNA Fragmentation: A Prospective Cohort Study

Introduction Recent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis. High plasma cell free DNA (cf-DNA) concentrations have been shown to be associated with sepsis outcome. The origin of cf-DNA is unclear. Methods Total plasma cf-DNA was quantified directly in plasma and the amplifiable cf-DNA assessed using quantitative PCR in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococcae or Escherichia coli. The quality of cf-DNA was analyzed with a DNA Chip assay performed on 8 survivors and 8 nonsurvivors. Values were measured on days 1–4 after positive blood culture, on day 5–17 and on recovery. Results The maximum cf-DNA values on days 1–4 (n = 132) were markedly higher in nonsurvivors compared to survivors (2.03 vs 1.26 ug/ml, p<0.001) and the AUCROC in the prediction of case fatality was 0.81 (95% CI 0.69–0.94). cf-DNA at a cut-off level of 1.52 ug/ml showed 83% sensitivity and 79% specificity for fatal disease. High cf-DNA (>1.52 ug/ml) remained an independent risk factor for case fatality in a logistic regression model. Qualitative analysis of cf-DNA showed that cf-DNA displayed a predominating low-molecular-weight cf-DNA band (150–200 bp) in nonsurvivors, corresponding to the size of the apoptotic nucleosomal DNA. cf-DNA concentration showed a significant positive correlation with visually graded apoptotic band intensity (R = 0.822, p<0.001). Conclusions Plasma cf-DNA concentration proved to be a specific independent prognostic biomarker in bacteremia. cf-DNA displayed a predominating low-molecular-weight cf-DNA band in nonsurvivors corresponding to the size of apoptotic nucleosomal DNA.

High Plasma Level of Long Pentraxin 3 (PTX3) Is Associated with Fatal Disease in Bacteremic Patients: A Prospective Cohort Study

Introduction Long pentraxin 3 (PTX3) is an acute-phase protein secreted by various cells, including leukocytes and endothelial cells. Like C-reactive protein (CRP), it belongs to the pentraxin superfamily. Recent studies indicate that high levels of PTX3 may be associated with mortality in sepsis. The prognostic value of plasma PTX3 in bacteremic patients is unknown. Methods Plasma PTX3 levels were measured in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, β-hemolytic streptococcae and Escherichia coli, using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Values were measured on days 1–4 after positive blood culture, on day 13–18 and on recovery. Results The maximum PTX3 values on days 1–4 were markedly higher in nonsurvivors compared to survivors (44.8 vs 6.4 ng/ml, p<0.001) and the AUCROC in the prediction of case fatality was 0.82 (95% CI 0.73–0.91). PTX3 at a cut-off level of 15 ng/ml showed 72% sensitivity and 81% specificity for fatal disease. High PTX3 (>15 ng/ml) was associated with hypotension (MAP <70 mmHg)(OR 7.9;95% CI 3.3–19.0) and high SOFA score (≥4)(OR 13.2; 95% CI 4.9–35.4). The CRP level (maximum value on days 1 to 4) did not predict case fatality at any cut-off level in the ROC curve (p = 0.132). High PTX3 (>15 ng/ml) remained an independent risk factor for case fatality in a logistic regression model adjusted for potential confounders. Conclusions PTX3 proved to be a specific independent prognostic biomarker in bacteremia. PTX3 during the first days after diagnosis showed better prognostic value as compared to CRP, a widely used biomarker in clinical settings. PTX3 measurement offers a novel opportunity for the prognostic stratification of bacteremia patients.

New concepts in the pathogenesis, diagnosis and treatment of bacteremia and sepsis

Bacteremia and sepsis are major health concerns. Despite intensive research, there are only a limited number of successful treatment options, and it is difficult to see the forest for the trees when considering the pathogenesis of this condition. Studies in the last decade have shown that a major pathophysiologic event in sepsis is the progression from proinflammation to an immunosuppressive state. However, recent genome-based data indicate that sepsis-related inflammatory responses are highly variable, which calls in question the classic two-phase model of sepsis. Adequate and timely antimicrobial treatment is a cornerstone for survival in patients with bacteremia and sepsis. However, microbial resistance has emerged as an increasing challenge for clinicians and with an increasing number of resistant pathogens causing infections, selection of empiric antimicrobial treatment has become difficult. Treatment options currently under way are targeted to enhance immune responses, rebalance the regulation of the dysregulated immune system, remove endotoxin and block/inhibit apoptosis.

Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study.

Background Early diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection. Methods The study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA). Results The median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders. Conclusions A high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.

Soluble urokinase-type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study

The soluble form of urokinase‐type plasminogen activator (suPAR) was evaluated as an early prognostic marker of sepsis in patients with suspected infection.

Healthcare workers as vectors of infectious diseases

Nosocomial infections cause considerable morbidity and mortality. Healthcare workers (HCWs) may serve as vectors of many infectious diseases, many of which are not often primarily considered as healthcare-associated. The probability of pathogen transmission to patients depends on several factors, such as the characteristics of a pathogen, HCW and patient. Pathogens with high transmission potential from HCWs to patients include norovirus, respiratory infections, measles and influenza. In contrast, human immunodeficiency virus (HIV) and viral hepatitis are unlikely to be transferred. The prevention of HCW-associated transmission of pathogens include systematic vaccinations towards preventable diseases, continuous education, hand hygiene surveillance, active feedback and adequate staff resources.