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Long-Term Effects of Phased Implementation of Antimicrobial Stewardship in Academic ICUs: 2007–2015*

Morris, Andrew M. MD, SM1–4; Bai, Anthony MD5; Burry, Lisa PharmD3,5; Dresser, Linda D. PharmD4,5; Ferguson, Niall D. MD, MSc1,3,4,7; Lapinsky, Stephen E. MD1,3,7; Lazar, Neil M. MD1,4,7; McIntyre, Mark PharmD4,6; Matelski, John MSc1,4; Minnema, Brian MD1,2,8; Mok, Katie BScPharm3; Nelson, Sandra PharmD, MScQIPS3; Poutanen, Susan M. MD, MPH1,2,3,4,9; Singh, Jeffrey M. MD, MSc1,4,7; So, Miranda PharmD4,6; Steinberg, Marilyn RN3; Bell, Chaim M. MD, PhD1,3,4

doi: 10.1097/CCM.0000000000003514
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Objectives: Antimicrobial stewardship is advocated to reduce antimicrobial resistance in ICUs by reducing unnecessary antimicrobial consumption. Evidence has been limited to short, single-center studies. We evaluated whether antimicrobial stewardship in ICUs could reduce antimicrobial consumption and costs.

Design: We conducted a phased, multisite cohort study of a quality improvement initiative.

Setting: Antimicrobial stewardship was implemented in four academic ICUs in Toronto, Canada beginning in February 2009 and ending in July 2012.

Patients: All patients admitted to each ICU from January 1, 2007, to December 31, 2015, were included.

Interventions: Antimicrobial stewardship was delivered using in-person coaching by pharmacists and physicians three to five times weekly, and supplemented with unit-based performance reports. Total monthly antimicrobial consumption (measured by defined daily doses/100 patient-days) and costs (Canadian dollars/100 patient-days) before and after antimicrobial stewardship implementation were measured.

Measurements and Main Results: A total of 239,123 patient-days (57,195 patients) were analyzed, with 148,832 patient-days following introduction of antimicrobial stewardship. Antibacterial use decreased from 120.90 to 110.50 defined daily dose/100 patient-days following introduction of antimicrobial stewardship (adjusted intervention effect –12.12 defined daily dose/100 patient-days; 95% CI, –16.75 to –7.49; p < 0.001) and total antifungal use decreased from 30.53 to 27.37 defined daily doses/100 patient-days (adjusted intervention effect –3.16 defined daily dose/100 patient-days; 95% CI, –8.33 to 0.04; p = 0.05). Monthly antimicrobial costs decreased from $3195.56 to $1998.59 (adjusted intervention effect –$642.35; 95% CI, –$905.85 to –$378.84; p < 0.001) and total antifungal costs were unchanged from $1771.86 to $2027.54 (adjusted intervention effect –$355.27; 95% CI, –$837.88 to $127.33; p = 0.15). Mortality remained unchanged, with no consistent effects on antimicrobial resistance and candidemia.

Conclusions: Antimicrobial stewardship in ICUs with coaching plus audit and feedback is associated with sustained improvements in antimicrobial consumption and cost. ICUs with high antimicrobial consumption or expenditure should consider implementing antimicrobial stewardship programs.

1Department of Medicine, University of Toronto, Toronto, ON, Canada.

2Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, ON, Canada.

3Sinai Health System, Toronto, ON, Canada.

4University Health Network, Toronto, ON, Canada.

5Faculty of Medicine, Queen’s University, Kingston, ON, Canada.

6Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.

7Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

8Department of Medicine, North York General Hospital, Toronto, ON, Canada.

9Division of Medical Microbiology, Department of Laboratory Medicine and Pathobiology, Unversity of Toronto; Toronto, ON, Canada.

*See also p. 290.

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A resident research grant from Physicians’ Services Incorporated Foundation supported this study. The Sinai Health System-University Health Network Antimicrobial Stewardship Program, including all of the dynamic prospective audit and feedback activities involved in carrying out this project, is funded by Sinai Health System and University Health Network; its research and education mission, however, including development of its educational website at, was supported by an unrestricted grant from Pfizer Canada from 2012. Dr. Morris’ institution also received funding from the Ontario Ministry of Health and Long-Term Care Alternative Funding Plan Innovation Grant administered jointly by the Sinai Health System and University Health Network Department Medicine. Dr. Matelski disclosed work for hire, and he disclosed he is employed by the Biostatistics Research Unit (BRU) at University Health Network, Toronto, where he performed the data analysis for this project. Sinai Health System-University Health Network Antimicrobial Stewardship Program (to Dr. Morris) paid BRU hourly for the statistical analysis. Dr. Poutanen’s institution received funding from Merck (Advisory Board, travel reimbursement, speak honoraria), Accelerate Diagnostics (Advisory support, research support), Copan (Travel reimbursement), Paladin Lab (Advisory Board), Bio-Rad (research support), and bioMérieux (research support). Dr. Bell is supported by a Canadian Institutes for Health Research and Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care. Dr. Morris’s, Ms. Mok’s, and Drs. Nelson’s and Bell’s institutions received funding from Physicians’ Services Incorporated Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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