Risto Vuento

Effects of mode of delivery and necrotising enterocolitis on the intestinal microflora in preterm infants

To investigate the effects of mode of delivery and of necrotising enterocolitis on the faecal microflora, 140 infants born before 33 weeks of gestation were followed up for symptoms of necrotising enterocolitis. Stool samples for gas–liquid chromatography and culture were collected twice weekly, and, when necrotising enterocolitis was suspected, for 2 months. For each infant with necrotising enterocolitis (n=21), two control infants matched for birth weight and gestational age were selected from the remaining study population. In gas–liquid chromatography analysis, the faecal bacterial microflora of infants born via caesarean section differed significantly from the gut microflora of those born via the vaginal route. The intestinal microflora showed a significant alteration in the necrotising enterocolitis group at time of diagnosis. At the onset of necrotising enterocolitis, faecal colonisation with Enterococcus species and Candida albicans was significantly more frequent in symptomatic infants than in controls. In infants with positive blood cultures and positive intestinal biopsy cultures, concomitant stool samples revealed the same microbial pathogens. In conclusion, the intestinal microbial colonisation in preterm infants born by caesarean section differs from that in preterm infants born via the vaginal route. A significant change in faecal microbial colonisation seems to occur at the onset of necrotising enterocolitis. Pathogens detected in the stools at that time might have a causative role in the development of the disease.

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.

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.

An outbreak of Streptococcus equi subspecies zooepidemicus associated with consumption of fresh goat cheese

BackgroundStreptococcus equi subspecies zooepidemicus is a rare infection in humans associated with contact with horses or consumption of unpasteurized milk products. On October 23, 2003, the National Public Health Institute was alerted that within one week three persons had been admitted to Tampere University Central Hospital (TaYS) because of S. equi subsp. zooepidemicus septicaemia. All had consumed fresh goat cheese produced in a small-scale dairy located on a farm. We conducted an investigation to determine the source and the extent of the outbreak.MethodsCases were identified from the National Infectious Disease Register. Cases were persons with S. equi subsp. zooepidemicus isolated from a normally sterile site who had illness onset 15.9-31.10.2003. All cases were telephone interviewed by using a standard questionnaire and clinical information was extracted from patient charts. Environmental and food specimens included throat swabs from two persons working in the dairy, milk from goats and raw milk tank, cheeses made of unpasteurized milk, vaginal samples of goats, and borehole well water. The isolates were characterized by ribotyping and pulsed-field gel electrophoresis (PFGE).ResultsSeven persons met the case definition; six had septicaemia and one had purulent arthritis. Five were women; the median age was 70 years (range 54–93). None of the cases were immunocompromized and none died. Six cases were identified in TaYS, and one in another university hospital in southern Finland. All had eaten goat cheese produced on the implicated farm. S. equi subsp. zooepidemicus was isolated from throat swabs, fresh goat cheese, milk tank, and vaginal samples of one goat. All human and environmental strains were indistinguishable by ribotyping and PFGE.ConclusionThe outbreak was caused by goat cheese produced from unpasteurized milk. Outbreaks caused by S. equi subsp. zooepidemicus may not be detected if streptococcal strains are only typed to the group level. S. equi subsp. zooepidemicus may be a re-emerging disease if unpasteurized milk is increasingly used for food production. Facilities using unpasteurized milk should be carefully monitored to prevent this type of outbreaks.

Factors predisposing to acute and recurrent bacterial non-necrotizing cellulitis in hospitalized patients: a prospective case-control study

Acute non-necrotizing cellulitis is a skin infection with a tendency to recur. Both general and local risk factors for erysipelas or cellulitis have been recognized in previous studies using hospitalized controls. The aim of this study was to identify risk factors for cellulitis using controls recruited from the general population. We also compared patients with a history of previous cellulitis with those suffering a single episode, with regard to the risk factors: length of stay in hospital, duration of fever, and inflammatory response as measured by C-reactive protein (CRP) level and leukocyte count. Ninety hospitalized cellulitis patients and 90 population controls matched for age and sex were interviewed and clinically examined during the period April 2004 to March 2005. In multivariate analysis, chronic oedema of the extremity, disruption of the cutaneous barrier and obesity were independently associated with acute cellulitis. Forty-four (49%) patients had a positive history (PH) of at least one cellulitis episode before entering the study. Obesity and previous ipsilateral surgical procedure were statistically significantly more common in PH patients, whereas a recent (<1 month) traumatic wound was more common in patients with a negative history (NH) of cellulitis. PH patients had longer duration of fever and hospital stay, and their CRP and leukocyte values more often peaked at a high level than those of NH patients. Oedema, broken skin and obesity are risk factors for acute cellulitis. The inflammatory response as indicated by CRP level and leukocyte count is statistically significantly more severe in PH than NH patients.

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.

Acute Bacterial, Nonnecrotizing Cellulitis in Finland: Microbiological Findings

BACKGROUND Bacterial, nonnecrotizing cellulitis is a localized and often recurrent infection of the skin. The aim of this study was to identify the beta-hemolytic streptococci that cause acute nonnecrotizing cellulitis infection in Finland. METHODS A case-control study of 90 patients hospitalized for acute cellulitis and 90 control subjects was conducted during the period of April 2004-March 2005. Bacterial swab samples were obtained from skin lesions or any abrasion or fissured toe web. Blood culture samples were taken for detection of bacteremia. The patients, their household members, and control subjects were assessed for pharyngeal carrier status. beta-Hemolytic streptococci and Staphylococcus aureus were isolated and identified, and group A and G streptococcal isolates were further analyzed by T serotyping and emm and pulsed-field gel electrophoresis typing. RESULTS beta-Hemolytic streptococci were isolated from 26 (29%) of 90 patients, 2 isolates of which were blood-culture positive for group G streptococci, and 24 patients had culture-positive skin lesions. Group G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) was found most often and was isolated from 22% of patient samples of either skin lesions or blood, followed by group A Streptococcus, which was found in 7% of patients. Group G streptococci were also carried in the pharynx of 7% of patients and 13% of household members but was missing from control subjects. Several emm and pulsed-field gel electrophoresis types were present among the isolates. Six patients (7%) had recurrent infections during the study. In 2 patients, the group G streptococcal isolates recovered from skin lesions during 2 consecutive episodes had identical emm and pulsed-field gel electrophoresis types. CONCLUSIONS Group G streptococci, instead of group A streptococci, predominated in bacterial cellulitis. No clear predominance of a specific emm type was seen. The recurrent nature of cellulitis became evident during this study.

Invasive Group B Streptococcal Infections in Finland: A Population-based Study

We analyzed surveillance data on group B streptococcus (GBS) infection in Finland from 1995 to 2000 and reviewed neonatal cases of early-onset GBS infection in selected hospitals in 1999 to 2000. From 1995 to 2000, 853 cases were reported (annual incidence 2.2–3.0/100,000 population). We found 32–38 neonatal cases of early-onset GBS disease per year (annual incidence 0.6–0.7/1,000 live births). In five hospitals, 35% of 26 neonatal cases of early-onset GBS infection had at least one risk factor: prolonged rupture of membranes, preterm delivery, or intrapartum fever. Five of eight mothers screened for GBS were colonized. In one case, disease developed despite intrapartum chemoprophylaxis. Although the incidence of early-onset GBS disease in Finland is relatively low, some geographic variation exists, and current prevention practices are suboptimal. Establishing national guidelines to prevent perinatal GBS is likely to reduce the incidence of the disease.