Browsing by Author "Sligl, Wendy"

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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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    ItemOpen Access
    LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial
    (2022-03-04) Opgenorth, Dawn; Baig, Nadia; Fiest, Kirsten; Karvellas, Constantine; Kutsogiannis, Jim; Lau, Vincent; Macintyre, Erika; Senaratne, Janek; Slemko, Jocelyn; Sligl, Wendy; Wang, Xiaoming; Bagshaw, Sean M.; Rewa, Oleksa G.
    Abstract Background Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited. Methods The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions. Discussion LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients. Trial registration ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021