Short-course daptomycin lock and systemic therapy for catheter-related bloodstream infections: a retrospective cohort study in cancer patients with surgically implanted devices.

PURPOSE: Few in vivo studies have been reported describing efficacy and duration of antibiotic lock therapy (ALT) with daptomycin (DPT) for long-term catheter-related bloodstream infections (CRBSI) due to coagulase-negative staphylococci (CoNS). We retrospectively analysed the efficacy of short-course ALT with DPT in combination with systemic treatment (ST) for CoNS-associated CRBSI in our hospital. METHODS: Patients admitted for CoNS-associated CRBSI and treated with DPT as ALT and ST were retrospectively analysed. Success was defined as preservation of the catheter device 30 days after ending treatment. Catheter removal within 30 days of discontinuing treatment, for either microbiological documentation of CRBSI relapse or re-occurrence of unexplained fever, was considered as failure. RESULTS: Among 7610 patients admitted to the Departments of Internal Medicine/Infectious Diseases and Pneumology in Cannes from January 2013 to November 2015, we identified 28 episodes of CoNS-associated CRBSI. Seven patients died of cancer during follow-up. Thus, 21 episodes were analysed among 20 patients (median age 67 years, 12 males, all treated for neoplasia and carrying a port-a-cath® device). Staphylococcus epidermidis was the main agent responsible for CRBSI. Median duration of systemic and ALT DPT was 3 days, in combination with rifampin for 4 days and then generally followed by a switch to oral drugs, most frequently cotrimoxazole or linezolid, to achieve 14 median days of treatment. Clinical success and failure rates were 76% and 24%, respectively. CONCLUSIONS: Short-course DPT as ALT, combined with 14 days of ST, allowed conservative management of CoNS-associated CRBSI in surgically implanted-catheters in three-fourth of cases.

Prophylactic use of noninvasive ventilation in patients undergoing lung resectional surgery.

QUESTION OF THE STUDY: We studied whether prophylactic use of noninvasive pressure support ventilation (NIPSV) administered pre- and postoperatively may reduce the postoperative pulmonary function impairment. PATIENTS AND METHODS: Prospective randomized clinical trial. Thirty-nine patients with a preoperative FEV(1) <70% of the predicted value scheduled for elective lobectomy related to lung cancer were enrolled. Seven patients were excluded after enrollment. Patients were required to follow standard treatment without (control group, n=18) or with NIPSV (study group, n=14) during 7 days at home before surgery, and during 3 days postoperatively. Primary outcome variable was the changes on arterial blood gases on room air. RESULTS: Two hours after surgery, PaO(2), FVC and FEV(1) values were significantly better in the NIPSV group. On day 1, 2 and 3, PaO(2) was significantly improved in the NIPSV group. Also on day 1, FVC and FEV(1) improved significantly in the NIPSV group. The hospital stay was significantly longer in the control group than in the study group (p=0.04). The incidence of major atelectasis was 14.2% in the NIPSV group and 38.9% in the no-NIPSV group (p=0.15). ANSWER TO THE QUESTION: Prophylactic use of NIPSV in a pre- and postoperative manner significantly reduces pulmonary dysfunction after lung resection. As a result, recovery of preoperative respiratory function is accelerated.

Constitutive expression of IL-2Rbeta chain and its effects on IL-2-induced vascular leak syndrome.

IL-2-induced vascular leak syndrome (VLS) is an important mechanism explaining the toxic effects of this cytokine and limiting its therapeutic use. We previously characterized a mouse model of IL-2-induced pulmonary VLS used to demonstrate that NK lymphocytes are involved in early/acute phase VLS (after one IL-2 injection). We also showed that NK cells and polymorphonuclear neutrophils (PMN) are involved in the late/chronic phase of the syndrome (after four daily IL-2 injections). In this study we use our mouse model to evaluate the role played by the IL-2 receptor (IL-2R) in VLS induction. Mouse and human IL-2R are different since the mouse IL-2Rbeta chain does not recognize IL-2. Here, we compare the acute and late VLS responses in human IL-2Rbeta transgenic and C57BL/6 wild type mice. Parameters linked to early phase VLS (bronchoconstriction and PMN mobilization) are enhanced in human IL-2Rbeta transgenic mice. By contrast, parameters used to measure late events (protein leakage and edema) are similar in human IL-2Rbeta transgenic mice and C57BL/6 wild type animals. However, after four IL-2 injections, the cellular content of the bronchoalveolar lavage fluids was different between the two types of animals. This study also characterizes a humanized animal model that could be further used to study human IL-2 activity and side effects in vivo.

NK cells and polymorphonuclear neutrophils are both critical for IL-2-induced pulmonary vascular leak syndrome.

The mechanism of IL-2-induced vascular leak syndrome (VLS) is still poorly understood. Cells of both innate and adaptive immune systems have been implicated, but no definitive conclusions have been reached concerning their respective roles. In this study we report a new mouse model of IL-2-induced pulmonary VLS used to obtain a detailed analysis of the early events (sequestration of polymorphonuclear neutrophils and bronchoconstriction) and late events (modifications in the cell and protein content of bronchoalveolar lavages, followed by edema) that characterize this lung injury. This model and knockout animals are used to reconsider the importance of the different leukocyte lineages in early and late events. Recombinase-activating gene 2(-/-) mice are used to demonstrate that adaptive lymphocytes, including NK T cells, are not required for pulmonary VLS induction. By contrast, results obtained with newly described recombinase-activating gene 2(-/-)/IL-15(-/-) mice indicate that NK cells play a key role in both early and late events. In parallel, polymorphonuclear neutrophil depletion is used to evaluate the contributions made by these cells to the late alterations occurring in the lung. Furthermore, when used in combination with inhibition of NO synthase, granulocyte depletion was completely effective in protecting mice from the late events of IL-2-induced pulmonary VLS. Together our results indicate that both NK and PMN cells play a central role in the late events of IL-2-induced VLS.