A pilot randomized controlled trial of 7 versus 14 days of antibiotic treatment for bloodstream infection on non-intensive care versus intensive care wards
Open Access
- 15 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Trials
- Vol. 21 (1), 1-11
- https://doi.org/10.1186/s13063-019-4033-9
Abstract
The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards. We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients. A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1–4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001). Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients. It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results. Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016.Funding Information
- Ontario Ministry of Health and Long-Term Care (NA)
- Canadian Institute of Health Research (410006728)
- Canadian Frailty Network (CAT2017-08)
This publication has 14 references indexed in Scilit:
- Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled TrialClinical Infectious Diseases, 2018
- Shortening Antibiotic Treatment Durations for BacteremiaClinical Infectious Diseases, 2018
- Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone ResistanceJAMA, 2018
- 7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trialTrials, 2018
- Trial of Short-Course Antimicrobial Therapy for Intraabdominal InfectionThe New England Journal of Medicine, 2015
- Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE): study protocol for a pilot randomized controlled trialTrials, 2015
- Antibiotic treatment duration for bloodstream infections in critically ill patients: a national survey of Canadian infectious diseases and critical care specialistsInternational Journal of Antimicrobial Agents, 2011
- Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysisCritical Care, 2011
- The design and interpretation of pilot trials in clinical research in critical careCritical Care Medicine, 2009
- Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock*Critical Care Medicine, 2006