Delayed increase of S100A9 messenger RNA predicts hospital-acquired infection after septic shock.

OBJECTIVE: Septic shock remains a serious disease with high mortality and increased risk of hospital-acquired infection. The prediction of outcome is of the utmost importance for selecting patients for therapeutic strategies aiming to modify the immune response. The aim of this study was to assess the capability of S100A9 messenger RNA in whole blood from patients with septic shock to predict survival and the occurrence of hospital-acquired infection. DESIGN: Cohort study. SETTING: Two intensive care units in a university hospital. SUBJECTS: The study included patients with septic shock (n = 166) and healthy volunteers (n = 44). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the patients with septic shock patients, overall mortality was 38% and the mean Simplified Acute Physiologic Scale II on shock onset was 52. Using quantitative reverse transcriptase-polymerase chain reactions, we found that median S100A9 messenger RNA was significantly lower in healthy volunteers than in patients with septic shock (p < .0001) between days 1 and 3 after onset of the septic shock and not significantly different between nonsurvivor and survivor patients (p = .1278). However, median S100A9 messenger RNA measured on days 7-10 was significantly higher in patients who were about to contract hospital-acquired infections compared with those who were not (p = .009). In the multivariate analysis, the S100A9 marker increased the probability of contracting hospital-acquired infections with an odds ratio of 1.12 per unit (p = .0054). CONCLUSIONS: S100A9 messenger RNA is increased in septic shock and its delayed overexpression is associated with the occurrence of secondary hospital-acquired infection. This biomarker may be of major interest in identifying patients with increased risk of hospital-acquired infection who could benefit from targeted therapy aimed at restoring their immune functions.

Early assessment of leukocyte alterations at diagnosis of septic shock.

A dramatic decrease in circulating lymphocyte number is regularly described after septic shock. However, it is unknown how early this alteration develops after diagnosis of shock and if it remains stable over time. Twenty-one septic shock patients with no comorbidities were included within 2 h after the beginning of vasopressive treatment. Flow cytometry phenotyping of circulating leukocyte subpopulations and quantitative real-time polymerase chain reaction of T-bet, GATA-3, FOXP3, and RORγ mRNA were performed in patients from the diagnosis of shock and every 6 h during the subsequent 48 h. From their admission in the intensive care unit, patients present with major alterations of circulating leukocyte count (leukocytosis, neutrophilia, and major lymphopenia). The numbers of every lymphocyte subpopulations (T, B, and natural killer cells) were diminished. Gene expression analysis of transcription factors specific for TH1, TH2, CD4CD25 regulatory, and TH17 lymphocytes showed a severe decrease in comparison with healthy individuals' values. These alterations remain stable during the first 48 h after inclusion in the protocol despite early and aggressive resuscitation and antibiotherapy administered in patients. At the time of diagnosis of shock and admission in the intensive care unit, septic patients already present with severe lymphopenia involving every lymphocyte subsets including CD4 T-cell subpopulations. No significant variation could be detected within the first 48 h. This should be taken into account in the forthcoming clinical trials testing immunomodulating therapies in septic shock patients.

Aneruptive fever associated with antibodies to Rickettsia helvetica in Europe and Thailand.

We report that eight patients from France, Italy, and Thailand had serological evidence of Rickettsia helvetica infection. The infection presented as a mild disease in the warm season and was associated with fever, headache, and myalgia but not with a cutaneous rash. R. helvetica should be suspected in patients with unexplained fever, especially following a bite from an Ixodes sp. tick.