Bacteraemic urinary tract infections may mimic respiratory infections: a nested case-control study.

Daily practice suggests that respiratory signs may be observed in bacteraemic urinary infections (BUI). Our objective was to search for an association between the presence of respiratory symptoms and the bacteraemic nature of urinary tract infections (UTI). A nested case-control study was carried out based on our computerised dashboard from January 2011 to June 2015. Cases were defined as patients with a BUI due to Enterobacteriaceae species, identified in blood and urine cultures. Controls had fever and a positive urinary sample but sterile blood cultures (NBUI) and a final diagnosis of urinary infection. Patients from the BUI group were 1:1 matched to the NBUI group according to four parameters: age, gender, cardiovascular and pulmonary comorbid conditions. Subjects with cognitive impairment limiting clinical accuracy and those with healthcare-associated infections were excluded. We compared systematically recorded respiratory and urinary symptoms between groups: signs on auscultation, dyspnoea, chest pain, cough and sputum, dysuria with burning, pollakiuria, flank or costovertebral angle tenderness and ischuria. One hundred BUI were compared to 100 NBUI, both groups exhibiting a similar rate for all considered comorbid conditions. In the BUI group, 58 % showed at least one respiratory sign vs. 20 % in the NBUI group, p < 0.001, while urinary signs were less frequent: 54 % vs. 71 %, p = 0.013. In the multivariate analysis, BUI was associated with the presence of abnormal pulmonary auscultation [adjusted odds ratio (AOR), 5.91; p < 0.001] and a trend towards less urinary symptoms (AOR, 1.58; p = 0.058). Patients with BUI presented with significantly more respiratory signs, which overshadowed urinary symptoms, compared to those with non-bacteraemic UTI. Such observations impact clinical decision-making.

Early infectious acute respiratory distress syndrome is characterized by activation and proliferation of alveolar T-cells.

Acute respiratory distress syndrome (ARDS) in humans is characterized by the infiltration of polymorphonuclears in the alveolar spaces. However, the role of T-cells in ARDS is unknown. Our aim was to characterize the T-cell phenotype in bronchoalveolar lavage (BAL) during the early phase of acute lung infection(ALI)/ARDS-infected patients in comparison to a control group (CG). BAL lymphocyte phenotypes of two ALI, 16 ARDS, and eight CG were examined by flow cytometry. ALI/ARDS showed a significant increase in CD4 and CD8 T-cell activation as compared to CG. Moreover, a significant level of proliferation was observed using the Ki67 marker in ARDS patients as compared to controls (median): 37 versus 6 % for CD4 T-cells (p = 0.022) and 34 versus 2 % for CD8 T-cells (p = 0.009). In contrast, the percentage of T-regulatory cells and apoptotic T-cells were similar in both groups. Among costimulatory molecules, we observed an overexpression of CTLA-4/CD152 on CD4 T-cells in ALI/ARDS as compared to CG: 30 versus 7 %, respectively (p = 0.063). In further characterizing T-cell subsets expressing high levels of CD152, we found the presence of IL-17 secreting CD4 T-cells in ALI/ARDS. In humans, ALI/ARDS due to infection is associated with a high level of T-cell activation and proliferation, along with the presence of Th17 cells, which are known to attract polymorphonuclears.

The suppression of immune activation during enfuvirtide-based salvage therapy is associated with reduced CCR5 expression and decreased concentrations of circulating interleukin-12 and IP-10 during 48 weeks of longitudinal follow-up.

BACKGROUND: It has been suggested that patients who initiate highly active antiretroviral therapy (HAART) late in their course of infection may have suboptimal CD4 T-cell gains, persistent alterations in T-cell subsets and residual inflammation. To address this issue, we carried out a comprehensive 48-week immunological study in HIV-infected patients who had experienced failures of prior therapies, had low CD4 cell counts, and were receiving enfuvirtide-based salvage therapy. METHODS: Immunological monitoring of peripheral lymphocytes from enfuvirtide-responder patients was performed over a 48-week period. A detailed assessment of immune cell subsets, their activation state [CD38 and human leucocyte antigen (HLA)-DR expression] and homeostasis [activation-induced cell death (AICD) and Ki67 expression], and the expression of co-receptors was performed by flow cytometry. Cytokine and chemokine signatures were assessed using multianalyte profiling technology. RESULTS: Enfuvirtide-based salvage therapy induced a progressive restoration of naïve and central memory CD4 T cells, associated with a decrease in their activation state, suppression of premature priming for AICD and increased expression of Ki67. In addition, a significant decrease in C-C chemokine receptor 5 (CCR5) expression was detected on CD4 T cells, which was strongly correlated with the suppression of immune activation. Changes in circulating proinflammatory molecules occurred; i.e. there were decreases in the concentrations of interleukin (IL)-12, macrophage inflammatory protein MIP-1α, MIP-1ß, monokine induced by IFNγ (MIG) and interferon-γ-inducible protein-10 (IP-10). The decline in circulating IL-12 and IP-10 was correlated with both the reduction in the viral load and CD4 T-cell restoration. CONCLUSIONS: This study shows that suppression of HIV-1 replication with enfuvirtide-based salvage therapy in patients with low CD4 cell counts may result in an immunological benefit, characterized by the restoration of CD4 T-cell subsets associated with decreased immune activation and suppression of inflammation.