Prospective, randomized study comparing quinupristin-dalfopristin with linezolid in the treatment of vancomycin-resistant Enterococcus faecium infections

OBJECTIVES: Quinupristin-dalfopristin and linezolid have been shown to be efficacious in the treatment of vancomycin-resistant Enterococcus faecium (VREF) infections. However, the two antibiotics have not been compared in terms of safety and efficacy in a prospective randomized study. The objective of this study was to compare the safety and efficacy of the two drugs in the treatment of VREF infections in cancer patients. PATIENTS AND METHODS: Forty cancer patients with VREF infection were randomized to receive linezolid 600 mg every 12 h or quinupristin-dalfopristin 7.5 mg/kg every 8 h. All patients were followed up for 30 days after discontinuation of study drugs. RESULTS: Linezolid and quinupristin-dalfopristin had comparable clinical responses (58% and 43%, respectively, P = 0.6). Myalgias and/or arthralgias occurred at a frequency of 33% in patients who received quinupristin-dalfopristin, but were not observed in the linezolid group (P = 0.03). In contrast, drug-related thrombocytopenia occurred in 11% of patients who received linezolid, but was not observed in the quinupristin-dalfopristin group (P = 0.2). CONCLUSION: In cancer patients, quinupristin-dalfopristin treatment is associated with a relatively high frequency of myalgias/arthralgias; however, profound thrombocytopenia might limit the choice of linezolid in a subpopulation of cancer patients.     

Microparticles from apoptotic monocytes enhance nitrosative stress in human endothelial cells

Microparticles are membrane vesicles with procoagulant and proinflammatory properties released during cell activation or apoptosis. Microparticles from monocytes have been implicated in atherosclerosis and vascular inflammation, but their direct effects on endothelial cells are not completely elucidated. The present study was designed to dissect the signaling pathways of monocytic microparticles in endothelial cells with respect to both NO pathway and reactive oxygen species. Microparticles were produced by treatment of human monocytic cell line THP-1 with the apoptotic agent VP-16. Human endothelial cells were treated with monocytic microparticles and then, we studied their effects on nitrosative and oxidative stresses. Incubation of human endothelial cells with microparticles enhanced the production of NO without affecting superoxide anions generation. Microparticles did not affect endothelial NO synthase expression and its phosphorylation. Interestingly, microparticles decreased caveolin-1 expression and increased its phosphorylation. Inhibition of PI-3-kinase or MEK1/2 reversed the effects of microparticles on caveolin-1 expression but not its phosphorylation. Moreover, microparticles increased nitration of several proteins, reflecting peroxynitrite production, which was prevented by blockade of PI-3-kinase pathway. In summary, monocyte microparticles active multiple pathways related to nitrosative stress in endothelial cells including both PI-3-kinase and ERK1/2 in the regulation of caveolin-1 expression. These data underscore the pleiotropic effect of microparticles on endothelial cells and suggest that they probably play a critical role on vascular function.     

Neuropathie axonale révélant un lymphome pleural primitif sur séquelles de collapsothérapie

Peripheral neuropathy is a rare presenting feature of malignant lymphoma, and commonly associated with diagnostic delay. We report a patient with axonal neuropathy revealing primary pleural lymphoma as a late outcome of pulmonary tuberculosis. A 72-year-old-man with a past medical history of pulmonary tuberculosis presented with a 5-month history of axonal neuropathy. The patient complained of chest pain, altered general status. Chest computed tomography (CT) showed pleural tumour invading the chest wall and CT-guided pleural biopsy revealed a B-cell lymphoma. Chemotherapy was not started in consideration of the poor performance status of the patient. Despite corticosteroids, the peripheral neuropathy worsened and the patient died 2 months after the diagnosis of lymphoma. To our knowledge, no previous case of peripheral neuropathy revealing pleural lymphoma has been reported. The diagnosis of lymphoma must be entertained in the presence of peripheral neuropathy of unknown aetiology. Neuropathy associated to lymphoma results from various mechanisms and is characterised by clinical polymorphism. Their prognosis depends on the mechanism of the neuropathy and the severity of the lymphoma.