Browsing by Author "Charbonney, Emmanuel"

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    7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial
    (2018-02-17) Daneman, Nick; Rishu, Asgar H; Pinto, Ruxandra; Aslanian, Pierre; Bagshaw, Sean M; Carignan, Alex; Charbonney, Emmanuel; Coburn, Bryan; Cook, Deborah J; Detsky, Michael E; Dodek, Peter; Hall, Richard; Kumar, Anand; Lamontagne, Francois; Lauzier, Francois; Marshall, John C; Martin, Claudio M; McIntyre, Lauralyn; Muscedere, John; Reynolds, Steven; Sligl, Wendy; Stelfox, Henry T; Wilcox, M. E; Fowler, Robert A
    Abstract Background Shorter-duration antibiotic treatment is sufficient for a range of bacterial infections, but has not been adequately studied for bloodstream infections. Our systematic review, survey, and observational study indicated equipoise for a trial of 7 versus 14 days of antibiotic treatment for bloodstream infections; a pilot randomized clinical trial (RCT) was a necessary next step to assess feasibility of a larger trial. Methods We conducted an open, pilot RCT of antibiotic treatment duration among critically ill patients with bloodstream infection across 11 intensive care units (ICUs). Antibiotic selection, dosing and route were at the discretion of the treating team; patients were randomized 1:1 to intervention arms consisting of two fixed durations of treatment – 7 versus 14 days. We recruited adults with a positive blood culture yielding pathogenic bacteria identified while in ICU. We excluded patients with severe immunosuppression, foci of infection with an established requirement for prolonged treatment, single cultures with potential contaminants, or cultures yielding Staphylococcus aureus or fungi. The primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. Secondary outcomes included 90-day, ICU and hospital mortality, relapse of bacteremia, lengths of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile, antibiotic adverse events, and secondary infection with antimicrobial-resistant organisms. Results We successfully achieved our target sample size (n = 115) and average recruitment rate of 1 (interquartile range (IQR) 0.3–1.5) patient/ICU/month. Adherence to treatment duration was achieved in 89/115 (77%) patients. Adherence differed by underlying source of infection: 26/31 (84%) lung; 18/29 (62%) intra-abdominal; 20/26 (77%) urinary tract; 8/9 (89%) vascular-catheter; 4/4 (100%) skin/soft tissue; 2/4 (50%) other; and 11/12 (92%) unknown sources. Patients experienced a median (IQR) 14 (8–17) antibiotic-free days (of the 28 days after blood culture collection). Antimicrobial-related adverse events included hepatitis in 1 (1%) patient, Clostridium difficile infection in 4 (4%), and secondary infection with highly resistant microorganisms in 10 (9%). Ascertainment was complete for all study outcomes in ICU, in hospital and at 90 days. Conclusion It is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival. Trial registration ClinicalTrials.gov , identifier: NCT02261506 . Registered on 26 September 2014.
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    National Preclinical Sepsis Platform: developing a framework for accelerating innovation in Canadian sepsis research
    (2021-03-19) Mendelson, Asher A; Lansdell, Casey; Fox-Robichaud, Alison E; Liaw, Patricia; Arora, Jaskirat; Cailhier, Jean-François; Cepinskas, Gediminas; Charbonney, Emmanuel; dos Santos, Claudia; Dwivedi, Dhruva; Ellis, Christopher G; Fergusson, Dean; Fiest, Kirsten; Gill, Sean E; Hendrick, Kathryn; Hunniford, Victoria T; Kowalewska, Paulina M; Krewulak, Karla; Lehmann, Christian; Macala, Kimberly; Marshall, John C; Mawdsley, Laura; McDonald, Braedon; McDonald, Ellen; Medeiros, Sarah K; Muniz, Valdirene S; Osuchowski, Marcin; Presseau, Justin; Sharma, Neha; Sohrabipour, Sahar; Sunohara-Neilson, Janet; Vázquez-Grande, Gloria; Veldhuizen, Ruud A W; Welsh, Donald; Winston, Brent W; Zarychanski, Ryan; Zhang, Haibo; Zhou, Juan; Lalu, Manoj M
    Abstract Despite decades of preclinical research, no experimentally derived therapies for sepsis have been successfully adopted into routine clinical practice. Factors that contribute to this crisis of translation include poor representation by preclinical models of the complex human condition of sepsis, bias in preclinical studies, as well as limitations of single-laboratory methodology. To overcome some of these shortcomings, multicentre preclinical studies—defined as a research experiment conducted in two or more research laboratories with a common protocol and analysis—are expected to maximize transparency, improve reproducibility, and enhance generalizability. The ultimate objective is to increase the efficiency and efficacy of bench-to-bedside translation for preclinical sepsis research and improve outcomes for patients with life-threatening infection. To this end, we organized the first meeting of the National Preclinical Sepsis Platform (NPSP). This multicentre preclinical  research collaboration of Canadian sepsis researchers and stakeholders was established to study the pathophysiology of sepsis and accelerate movement of promising therapeutics into early phase clinical trials. Integrated knowledge translation and shared decision-making were emphasized to ensure the goals of the platform align with clinical researchers and patient partners. 29 participants from 10 independent labs attended and discussed four main topics: (1) objectives of the platform; (2) animal models of sepsis; (3) multicentre methodology and (4) outcomes for evaluation. A PIRO model (predisposition, insult, response, organ dysfunction) for experimental design was proposed to strengthen linkages with interdisciplinary researchers and key stakeholders. This platform represents an important resource for maximizing translational impact of preclinical sepsis research.