Early Antibiotic Discontinuation or De-escalation in High-Risk Patients With AML With Febrile Neutropenia and Prolonged Neutropenia

Authors:
William Alegria Stanford Antimicrobial Safety and Sustainability Program, Stanford Health Care, and
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California; and

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Bernard L. Marini Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan;
University of Michigan, College of Pharmacy, Ann Arbor, Michigan; and

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Kevin Sellery Gregg Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan;
Division of Infectious Diseases, and

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Dale Lee Bixby Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan;
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.

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Anthony Perissinotti Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan;
University of Michigan, College of Pharmacy, Ann Arbor, Michigan; and

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Jerod Nagel Department of Pharmacy Services, Michigan Medicine, Ann Arbor, Michigan;
University of Michigan, College of Pharmacy, Ann Arbor, Michigan; and

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Background: There is minimal data evaluating the safety of antibiotic de-escalation in patients with acute myeloid leukemia (AML) with fever and ongoing neutropenia. Therefore, this study evaluated antibiotic prescribing, infection-related outcomes, and patient outcomes of an antibiotic de-escalation initiative. Patients and Methods: This pre–post quasiexperimental study included adult patients with AML hospitalized with febrile neutropenia. An antibiotic de-escalation guideline was implemented in January 2017, which promoted de-escalation or discontinuation of intravenous antipseudomonal β-lactams. The primary outcome assessment was the incidence of bacterial infection in a historical control group before guideline implementation compared with an intervention group after guideline implementation. Results: A total of 93 patients were included. Antibiotic de-escalation occurred more frequently in the intervention group (71.7% vs 7.5%; P<.001), which resulted in fewer days of therapy for intravenous antipseudomonal β-lactams (14 vs 25 days; P<.001). Thirty-day all-cause mortality and length of hospitalization were not different between groups. However, the intervention group had significantly fewer episodes of Clostridioides difficile colitis (5.7% vs 27.5%; P=.007). Conclusions: Implementation of an antibiotic de-escalation guideline resulted in decreased use of intravenous antipseudomonal β-lactams and fewer episodes of C difficile colitis, without adversely impacting patient outcomes. Additional studies are needed, preferably in the form of randomized controlled trials, to confirm these results.

Submitted October 30, 2019; final revision received April 26, 2021; accepted for publication April 27, 2021. Published online February 4, 2022.

Author contributions: All authors helped develop the project, implement the intervention, analyze the results, and develop the manuscript.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Jerod Nagel, PharmD, BCIDP, University of Michigan Hospital, 1111 East Catherine Street, Room 311, Ann Arbor, MI 48109. Email: nageljl@umich.edu
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