Jan-Erik Berdal

Excessive innate immune response and mutant D222G/N in severe A (H1N1) pandemic influenza.

AIM Explore the role of viral factors and immune response in patients with severe pandemic pdmH1N1 illness without significant co-morbidity. MATERIALS Seven patients with pdmH1N1 influenza, bilateral chest X-rays infiltrates, requiring mechanical ventilator support were consecutively recruited. Seven age- and gender-matched healthy individuals served as controls. RESULTS Four patients were viremic, two with the mutant D222G/N pdmH1N1.Microarray analyses of peripheral blood leukocytes suggested a marked granulocytes activation, but no up-regulation of inflammatory cytokine mRNA. Patients with severe pdmH1NI had a marked systemic complement activation, and in contrast to the lack of cytokine mRNA up-regulation in blood leukocytes, plasma levels of a broad range of inflammatory mediators, including IP-10, and mediators involved in pulmonary remodelling were markedly elevated. Patients with mutant virus had particularly high IP-10 levels, and the most pronounced complement activation. CONCLUSIONS In severe pdmH1N1, viremia was common and the D222G/N mutant was found in half of the viremic patients. Host immune response was characterized by strong activation of the innate immune system, including complement and granulocytes activation, increased serum levels of inflammation and pulmonary remodelling markers, possibly contributing to the observed tissue damage. However, few patients were included and further studies are needed to characterize the immune response in severe pdmH1N1 infection.

Nosocomial candidemia; risk factors and prognosis revisited; 11 years experience from a Norwegian secondary hospital.

The aim of the study was to review the epidemiology and prognosis of candidemia in a secondary hospital, and to examine the intra-hospital distribution of candidemia patients. Study design is a retrospective cohort study. Trough 2002–2012, 110 cases of candidemia were diagnosed, giving an incidence of 2, 6/100000 citizens/year. Overall prognosis of candidemia was dismal, with a 30 days case fatality rate of 49% and one year case fatality rate of 64%. Candidemia was a terminal event in 55% of 30 days non-survivors, defined as Candida blood cultures reported positive on the day of death or thereafter (39%), or treatment refrained due to hopeless short-term prognosis (16%). In terminal event candidemias, advanced or incurable cancer was present in 29%. Non-survivors at 30 days were 9 years (median) older than survivors. In 30 days survivors, candidemia was not recognised before discharge in 13% of cases. No treatment were given and no deaths or complications were observed in this group. Candidemia patients were grouped into 8 patient categories: Abdominal surgery (35%), urology (13%), other surgery (11%), pneumonia (13%), haematological malignancy (7%), intravenous drug abuse (4%), other medical (15%), and new-borns (3%). Candidemia was diagnosed while admitted in the ICU in 46% of patients. Urology related cases were all diagnosed in the general ward. Multiple surgical procedures were done in 60% of abdominal surgery patients. Antibiotics were administered prior to candidemia in 87% of patients, with median duration 17 (1–108) days. Neutropenia was less common than expected in patients with candidemia (8/105) and closely associated to haematological malignancy (6/8). Compared with previous national figures the epidemiology of invasive candidiasis seems not to have changed over the last decade.

Short-term success, but long-term treatment failure with linezolid for enterococcal endocarditis.

We report a case of linezolid treatment failure for Enterococcus faecalis endocarditis. Despite success during and shortly after treatment, the patient had a relapse after 7 weeks. Due to prior anaphylactic reaction to penicillin, desensitization was performed, and successful penicillin therapy given. The efficacy of linezolid for enterococcal endocarditis remains questionable.

Prognostic merit of N-terminal-proBNP and N-terminal-proANP in mechanically ventilated critically ill patients

Background: Amino‐terminal fragments of type‐A and type‐B natriuretic peptide prohormones (NT‐proBNP, NT‐proANP) are powerful prognostic markers in patients with cardiac disease, and NT‐proBNP has been demonstrated to predict outcome in severe sepsis and septic shock. We assessed the prognostic value of NT‐proBNP and NT‐proANP in a consecutive series of mechanically ventilated intensive care patients and compared their prognostic merit.

Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway

Increased understanding of immune responses influencing clinical severity during pandemic influenza infection is important for improved treatment and vaccine development. In this study we recruited 46 adult patients during the 2009 influenza pandemic and characterized humoral and cellular immune responses. Those included were either acute hospitalized or convalescent patients with different disease severities (mild, moderate or severe). In general, protective antibody responses increased with enhanced disease severity. In the acute patients, we found higher levels of TNF-α single-producing CD4+T-cells in the severely ill as compared to patients with moderate disease. Stimulation of peripheral blood mononuclear cells (PBMC) from a subset of acute patients with peptide T-cell epitopes showed significantly lower frequencies of influenza specific CD8+ compared with CD4+ IFN-γ T-cells in acute patients. Both T-cell subsets were predominantly directed against the envelope antigens (HA and NA). However, in the convalescent patients we found high levels of both CD4+ and CD8+ T-cells directed against conserved core antigens (NP, PA, PB, and M). The results indicate that the antigen targets recognized by the T-cell subsets may vary according to the phase of infection. The apparent low levels of cross-reactive CD8+ T-cells recognizing internal antigens in acute hospitalized patients suggest an important role for this T-cell subset in protective immunity against influenza.

Culture-negative severe septic shock: indications for streptococcal aetiology based on plasma antibodies and superantigenic activity.

We present a severe septic shock syndrome patient with negative blood cultures. Acute and convalescent plasma samples from the patient were analysed for anti-streptolysin O titres, superantigen-neutralizing activity and presence of superantigenic activity. The plasma analyses implicated superantigen-producing Streptococcus pyogenes as the causative agent.

Does Pseudomonas aeruginosa colonization influence morbidity and mortality in the intensive care unit patient? Experience from an outbreak caused by contaminated oral swabs.

Background:  Contaminated oral swabs caused a nationwide monoclonal Pseudomonas aeruginosa outbreak involving 27 Norwegian hospitals. The aim of the study was to study the consequences on mortality and morbidity of the introduction of this P. aeruginosa strain to intensive care unit (ICU) patients.