Browsing by Author "Daneman, Nick"

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    ItemOpen Access
    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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    Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial
    (2021-05-04) Bégin, Philippe; Callum, Jeannie; Heddle, Nancy M; Cook, Richard; Zeller, Michelle P; Tinmouth, Alan; Fergusson, Dean A; Cushing, Melissa M; Glesby, Marshall J; Chassé, Michaël; Devine, Dana V; Robitalle, Nancy; Bazin, Renée; Shehata, Nadine; Finzi, Andrés; McGeer, Allison; Scales, Damon C; Schwartz, Lisa; Turgeon, Alexis F; Zarychanski, Ryan; Daneman, Nick; Carl, Richard; Amorim, Luiz; Gabe, Caroline; Ellis, Martin; Sachais, Bruce S; Loftsgard, Kent C; Jamula, Erin; Carruthers, Julie; Duncan, Joanne; Lucier, Kayla; Li, Na; Liu, Yang; Armali, Chantal; Kron, Amie; Modi, Dimpy; Auclair, Marie-Christine; Cerro, Sabrina; Avram, Meda; Arnold, Donald M
    Abstract Background Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection. Methods CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600). Discussion This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification. Trial registration Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.
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    Regional variation in the potentially inappropriate first-line use of fluoroquinolones in Canada as a key to antibiotic stewardship? A drug utilization review study
    (2021-08-03) St-Jean, Audray; Chateau, Dan; Dahl, Matthew; Ernst, Pierre; Daneman, Nick; Sketris, Ingrid S.; Zhang, Jianguo; Marra, Fawziah; Quail, Jacqueline; Bugden, Shawn
    Abstract Background Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada. Methods Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit. Results We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD. Conclusions Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones.