Cefazolin-Induced Neutropenia Development and Evaluation of Risk Factors in Home Infusion (CINDER-FHI)
Authors:   Fairview Health Services, Panchak Nicholas , McFarland Ryan ,   University of Minnesota-Duluth College of Pharmacy, Das Jessica ,   Fairview Health Services, Zagel Alicia ,   Fairview Health Services, Ross Jennifer ,   Fairview Health Services
Published: February 2025

Background: Beta-lactam-induced neutropenia (BLIN) is a serious adverse reaction associated with extended treatment courses. For many severe infections, guideline-directed medical therapy frequently involves weeks or months of IV antibiotics. To avoid health care costs associated with hospitalization and as a method to improve hospital bed capacity, clinicians are encouraged to discharge patients to receive IV antibiotics in the ambulatory setting once clinically stable. The purpose of this study was to compare the incidence of cefazolin-induced neutropenia between intravenous push (IVP) administration and intermittent infusions among home infusion patients. This study is unique in its analysis of neutropenia monitoring and interventions in a pharmacist-led outpatient parenteral anti-infective therapy (OPAT) model. Cefazolin was examined over other beta-lactams due to high utilization in home infusion and administration methods by IVP and intermittent infusion at this institution.

Methods: This was a retrospective cohort study within a single large health system that includes an associated home infusion pharmacy. Patients were included for analysis if they met the following criteria: ≥18 years of age, received cefazolin through the home infusion pharmacy between July 1, 2017, and July 1, 2022, and were discharged from an acute care site within the health system for index cefazolin episode to the home or an affiliated long-term care facility. Lab values within 2 weeks of the cefazolin treatment course were evaluated for neutropenia. The primary outcome was the incidence of neutropenia by the method of administration: IVP versus intermittent infusion. Patients who received intermittent infusions in this study utilized elastomeric devices or ambulatory infusion pumps. Duration of IVP and intermittent infusion were defined as being given over 10 minutes and 30 minutes, respectively.

Results: A total of 431 patients were included in the study. Home infusion pharmacists recorded 18 BLIN events. All patients were asymptomatic. Fourteen events were classified as mild, with an absolute neutrophil count (ANC) nadir of 1.1-1.5 cells×1000/μL. Two events were considered moderate and 2 were considered severe, with ANC nadirs between 0.5 to 1.0 cells×103/μL and <0.5 cells×103/μL, respectively.

Conclusions: The relationship between baseline ANC and the development of BLIN later in treatment reported a 3.4-fold increased risk of cefazolin-induced neutropenia, and individuals with neutrophil counts between 1.6×103 cells/μL and 3.9×103 cells/μL at baseline require the highest degree of care. Our data suggests that low absolute neutrophil count (ANC) at cefazolin initiation is the strongest risk factor for subsequent development of neutropenia.

Keywords: beta-lactams, home infusion, neutropenia, intravenous push, infusion