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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.

BackgroundThe pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host.Methodology/Principal FindingsBlood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs).Conclusions/SignificanceInfection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

Vancomycin-resistant enterococci (VRE) have emerged as significant nosocomial pathogens. A hospital-wide prevalence study was performed to identify cases with VRE faecal colonisation. A case-control study using two randomly selected VRE-negative controls for each positive case was performed to assess risk-factors for VRE colonisation by univariate and multivariate analysis. VRE faecal colonisation was documented in 53 (14.3%) of 370 patients screened. Previous exposure to anti-anaerobic agents, as well as quinolones, was associated with VRE colonisation (p <0.05). The presence of an invasive device (OR 4.8, p 0.003) and the duration of any antimicrobial treatment before VRE isolation (OR 1.2, p <0.001) predicted VRE colonisation in multivariate models. The crude mortality rate for patients with VRE colonisation was 24.5%, but VRE colonisation was not an independent predictor of mortality in these patients. These results suggest that an active surveillance programme focusing on specific patient groups may help in the identification of VRE-colonised patients. Promptly implemented infection control strategies targeting these groups should help to combat the rising incidence of VRE.

Background Chronic bacterial prostatitis (CBP) is a difficult-to-treat infection as only a few antibiotics achieve therapeutic concentrations in the prostate. Data on the efficacy and safety of oral fosfomycin for the treatment of CBP are limited. Objectives To analyse the efficacy and safety of fosfomycin in CBP due to MDR pathogens. Methods In a prospective observational study, an oral regimen of 3 g of fosfomycin q24h for 1 week followed by 3 g q48h for a treatment duration of 6–12 weeks was administered. The outcome was clinical and microbiological cure rate at the end of treatment (EOT) and rate of relapse at 3 and 6 months. Results The study included 44 patients. The most common pathogen was Escherichia coli (66%), followed by Klebsiella spp. (14%) and Enterococcus faecalis (14%). Most strains were MDR (59%) and 23% had an ESBL phenotype; 33 of 44 strains were resistant to fluoroquinolones, but all were susceptible to fosfomycin (median MIC for Gram-negative pathogens 1.5 mg/L). In 25 patients, treatment was administered for 6 weeks, whereas in the remaining 19 patients it was prolonged to 12 weeks based on the presence of calcifications in the prostate. Cure rate was 82% at EOT and 80% and 73% at 3 and 6 months accordingly. Microbiological eradication was achieved in 86% and 77% at EOT and at 6 months, respectively. Failure was observed in 12 patients. The most common adverse event was diarrhoea (18%). Conclusions Oral fosfomycin, particularly in the era of MDR prevalence, represents an attractive, safe and effective alternative to fluoroquinolones for the treatment of CBP.