7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial

• Published in: Current controlled trials in cardiovascular medicine Vol. 19; no. 1; p. 111
• Main Authors: 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 Elizabeth, Fowler, Robert A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.02.2018; BioMed Central; BMC
• Subjects: Aged; Analysis; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Antibiotics; Antimicrobial agents; Bacteremia; Bacteremia - diagnosis; Bacteremia - drug therapy; Bacteremia - microbiology; Bacterial infections; Bloodstream infection; Canada; Care and treatment; Clinical trials; Community-Acquired Infections - diagnosis; Community-Acquired Infections - drug therapy; Community-Acquired Infections - microbiology; Critical care; Critical Illness; Cross Infection - diagnosis; Cross Infection - drug therapy; Cross Infection - microbiology; Dosage and administration; Drug Administration Schedule; Duration of treatment; Feasibility Studies; Female; Health aspects; Health sciences; Humans; Immunotherapy; Infection; Intensive care; Intensive Care Units; Male; Middle Aged; Mortality; Nosocomial infections; Organisms; Pathogens; Patient outcomes; Patients; Pilot Projects; Prostheses; Time Factors; Treatment Outcome; Canada; Critical care; Duration of treatment; Intensive care; Bloodstream infection; Bacteremia
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-018-2474-1

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