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Background: Daptomycin is a recently developed cyclic lipopeptide antibiotic active against most Gram-positive pathogens including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To optimize treatment efficacy and safety, especially in patients undergoing multiple drug regimens and/or co-morbidities, a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of daptomycin in plasma. Methods: A C18 column was used for separation, with a mobile phase initially consisting of 0.1% formic acid, water, and acetonitrile (ACN) in a linear gradient from 20% to 70%. After protein precipitation with ACN, the clear upper layer was diluted in water:ACN (50:50, v/v) before injection. Detection was performed using an electrospray ionization technique. MS/MS transitions, monitored in the positive ion mode were m/z 811.1 → m/z 313.1 for daptomycin, and m/z 609.4 → m/z 194.9 for reserpine, used as internal standard. Results: Elution of daptomycin and reserpine occurred at 4.5 and 3.9 min, respectively. The method was validated over a range of concentrations from 1 mg/L to 120 mg/L. The assay met recommended acceptance criteria: coefficients of variation were Conclusions: This method appears well-adapted to routine hospital practice for therapeutic drug monitoring of daptomycin considering its time of analysis, range of concentrations measured, precision and accuracy.

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Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant bacteria responsible for invasive infections, including prosthetic joint infections (PJIs). Local administration of colistin may provide bactericidal concentrations in situ. This study evaluated the efficacy of a colistin-impregnated cement spacer, alone and in combination with systemic antibiotics, in a rabbit model of CPE-PJI. Elution of 3 MIU of colistimethate sodium (CMS) in 40 g of poly(methyl methacrylate) cement was studied in vitro. In vivo, 5 × 108 CFU of KPC-producing Klebsiella pneumoniae (colistin and meropenem MICs of 1 mg/L and 4 mg/L, respectively) were injected close to a prosthetic knee. Surgical debridement and prosthesis removal were performed 7 days later, and rabbits were assigned to six treatment groups (11–13 rabbits each): drug-free spacer; colistin-loaded spacer; colistin intramuscular (i.m.); colistin i.m. + colistin spacer; colistin i.m. + meropenem subcutaneous (s.c.); and colistin i.m. + meropenem s.c. + colistin spacer. Systemic treatment was administered at doses targeting pharmacokinetics in humans, and rabbits were euthanised 7 days later to evaluate bacterial counts in infected bones. In vitro, CMS elution was low ( 20 × MIC). In vivo, combinations of local and systemic colistin, with or without meropenem, were the only regimens superior to the control group (P ≤ 0.05) in terms of viable bacterial counts and the proportion of rabbits with sterile bone, with no emergence of colistin-resistant strains. Colistin-loaded cement spacer in combination with systemic antibiotics were the most effective regimens in this CPE-PJI model.

National audience; Objective To evaluate the impact of age (< or ≥ 65 ans) on hospital mortality in traumatic spinal cord injury requiring intensive care. Design Retrospective, monocenter. Patients and methods A total of 131 patients greater or equal to 15 years (< 65 years, n = 109 and ≥ 65 years, n = 22) was analyzed (cervical, n = 71; thoracolumbar, n = 60), over a 10 years period (1998-2008). The hospital and long-term mortality were studied. The risks factors of death were searched by a uni- and multivariate analysis. Intensive care unit (ICU) discharge and long-term neurological recovery, and long-term functional independence measure (FIM) were assessed. Results Hospital mortality was increased in patients greater or equal to 65 years (41% vs 6%, P < 0.001) and long term mortality was not different between the two groups (31% vs 12%, P = 0.150). The risks factors of death were age (HR = 3.44; IC 95%: 1.53-7.72, P = 0.028), previous coronary disease (HR = 3.64; IC 95%: 1.25-10.65; P = 0.018) and fall injury (HR = 2.40; IC 95%: 1.15-5.00, P = 0.020). Among survivors, incompletes forms (Frankel B, C, D, E) were significantly more frequent in older patients at ICU discharge and long term follow up. At long term, FIM was similar in the two groups except a better sphincter control in patient greater or equal to 65 years. Conclusion Mortality rate of older people (≥ 65 years) were greater than those in younger people, mainly caused by an increased hospital mortality. Among survivors, the neurological recovery was better in patients' greater or equal to 65 years, and was associated with a functional status at least comparable than in the youngest patients.

International audience; INTRODUCTION: Unawareness of an asymmetry between the right and left internal jugular vein (IJV) and methodological pitfalls in previous studies raise concerns about such asymmetry. Hence the aim of this prospective non-interventional study was to validate the hypothesis that right IJV diameter is greater than those of left IJV and to determine the cross-sectional area of the IJVs using computed tomography (CT)-scans and original automatic software. METHODS: All consecutive adult outpatients who underwent a thoracic contrast-enhanced (TCE) helical CT-scan during a 5-month period were included. To determine diameter and cross sectional area of the IJVs, we used Advanced Vessel Analysis software integrated in a CT-scan (Advanced Vessel Analysis on Advantage Workstation Windows 4.2; General Electrics) allowing automatic segmentation of vessels and calculation of their diameters and cross-sectional areas. RESULTS: A total of 360 TCE CT-scans was performed; 170 were excluded from the analysis. On the remaining 190 CT scans, the diameter and cross-sectional area of the right IJV were significantly greater than those of the left IJV (17 +/- 5 mm [median: 17 mm, range: 13 to 20 mm] vs. 14 +/- 5 mm [median: 13 mm, range: 10 to 16 mm], P < 0.001; and 181 +/- 111 mm2 [median: 160 mm2, range: 108 to 235 mm2] vs. 120 +/- 81 mm2 [median: 102 mm2, range: 63 to 168 mm2], P < 0.001, respectively). CONCLUSIONS: In a general population of adult outpatients, the diameter and cross-sectional area of the right IJV were significantly greater than those of the left IJV. This could be an additional argument to prefer right over left IJV cannulation.