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.
Original language | English |
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Article number | 111 |
Journal | Trials |
Volume | 19 |
Issue number | 1 |
DOIs | |
Publication status | Published - Feb 17 2018 |
Bibliographical note
Funding Information:Supported by grants from Ontario Ministry of Health and Long-Term Care Academic Health Sciences Centre Alternative Funding Plan (AFP) Innovation Fund Awards and Canadian Institute of Health Research (CIHR). Dr. Fowler’s work was supported by a personnel award from the Heart and Stroke Foundation, Ontario Provincial Office.
Funding Information:
Dr. Nick Daneman is supported by a Clinician Scientist salary award from the Canadian Institutes of Health Research (CIHR). Dr. Rob Fowler is supported by a personnel award from the Heart and Stroke Foundation, Ontario Provincial Office. Dr. Deborah Cook holds a Canada Research Chair of Research Transfer in Intensive Care. Drs. Lauzier and Lamontagne hold a career award from the Fonds de Recherche du Québec-Santé. Dr. John Marshall is an associate editor for Critical Care. Dr. Sean Bagshaw holds a Canada Research Chair in Critical Care Nephrology. Dr. HT Stelfox is supported by a Population Health Investigator Award from Alberta Innovates and an Embedded Clinician Researcher Award from CIHR. This pilot randomized controlled trial was supported by operating funds from the Ontario Ministry of Health and Long-Term Care Academic Health Sciences Alternate Funding Plan Innovation Fund Award, and bridge funding from the Canadian Institutes of Health Research. The BALANCE main trial is supported by a Project Grant from the Canadian Institutes of Health Research.
Publisher Copyright:
© 2018 The Author(s).
ASJC Scopus Subject Areas
- Medicine (miscellaneous)
- Pharmacology (medical)
PubMed: MeSH publication types
- Comparative Study
- Journal Article
- Multicenter Study
- Randomized Controlled Trial