IntroductionAlthough major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time.MethodsThe statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer.ResultsExpression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis.ConclusionsMajor differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.
Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.
Introduction Our aim was to define early changes of lymphocytes and of NK cells in severe sepsis and to correlate them with serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1).
We hypothesized that a factor may circulate in serum early during sepsis, modulating apoptosis of monocytes and lymphocytes. Serum was collected from 20 healthy volunteers and from 48 patients with severe sepsis/shock within 12 h from signs of the first failing organ. PBMCs were isolated from 20 healthy volunteers and incubated with collected sera. Apoptosis and expression of CD95 were determined by flow cytometry; experiments were run in the presence of caspase-8 and caspase-9 inhibitors and of CaCl(2). Activity of caspase-3 was determined in cell lysates by a chromogenic kinetic assay. Incubation with serum of patients induced apoptosis of CD4 lymphocytes and inhibited apoptosis of CD14 monocytes. This was attenuated after diluting serum or mixing with healthy serum. Activity of caspase-3 was consistent with these findings. Induced apoptosis of CD4 lymphocytes was greater among nonsurvivors, and it was inhibited in the presence of caspase inhibitors. Inhibitors did not modify the effect of patients' serum on apoptosis of CD14 monocytes. CaCl(2) reversed the inhibitory effect on apoptosis of CD14 moncytes. The above findings support the hypothesis for the existence of an early circulating factor in severe sepsis/shock, modulating apoptosis of CD4 lymphocytes and of CD14 monocytes by interaction with the two apoptotic pathways.
Candida species are a common cause of invasive infection in neonates and children. The aim of our study was to evaluate the epidemiology and microbiology of invasive candidiasis (IC) in the largest tertiary Greek pediatric hospital during a 10-year period. A retrospective cohort study was performed from January 2008 to December 2017. Identification of species and antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) methodology. During the study period, 178 cases of IC were recorded. The tissue distribution included blood (87.1%), cerebrospinal (7.9%), peritoneal (3.9%) and pleural fluids (1.1%). Candida albicans and Candida parapsilosis (sensu lato) were the most frequently isolated species (47.8% and 28.7% respectively). From period 2008–2012 to period 2013–2017, a significant decrease in IC rates was detected (0.21 cases/1000 hospitalization days VS 0.11 cases/1000 hospitalization days, P = 0.040), while median minimum inhibitory concentrations (MICs) of amphotericin B were significantly increased for both C. albicans and C. parapsilosis (sl) (P = 0.037 and P = 0.004 respectively). The decrease in IC rates may reflect the increased awareness as well as the effective infection control initiatives and antifungal interventions. However, the significant increase in the MICs for amphotericin B and echinocandins such as caspofungin, raises concerns about their common use as first-line treatment. Epidemiologic monitoring is, therefore, critically important in order to evaluate and optimize therapeutic protocols for IC in pediatric populations.
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