• Nick Daneman, Asgar H Rishu, Ruxandra Pinto, Pierre Aslanian, Sean M Bagshaw, Alex Carignan, Emmanuel Charbonney, Bryan Coburn, Deborah J Cook, Michael E Detsky, Peter Dodek, Richard Hall, Anand Kumar, Francois Lamontagne, Francois Lauzier, John C Marshall, Claudio M Martin, Lauralyn McIntyre, John Muscedere, Steven Reynolds, Wendy Sligl, Henry T Stelfox, M Elizabeth Wilcox, Robert A Fowler, and Canadian Critical Care Trials Group.
• Division of Infectious Diseases and Clinical Epidemiology, Sunnybrook Health Sciences Centre, University of Toronto and Adjunct Scientist, Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. nick.daneman@sunnybrook.ca.
• Trials. 2018 Feb 17; 19 (1): 111.

BackgroundShorter-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.MethodsWe 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.ResultsWe 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.ConclusionIt is feasible to conduct a RCT to determine whether 7 versus 14 days of antibiotic treatment is associated with comparable 90-day survival.Trial RegistrationClinicalTrials.gov , identifier: NCT02261506 . Registered on 26 September 2014.

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