Comparison of Neutropenia Associated with Ceftaroline or Ceftriaxone in Patients Receiving at Least 7 Days of Therapy for Severe Infections.

Study Objective: Ceftarolinefosamil is a cephalosporin with broad clinical utility; however, limited data suggest that prolonged ceftaroline exposure may be associated with neutropenia. The objective was to determine drug and patient factors associated with neutropenia in patients receiving ceftaroline or ceftriaxone for deep‐seated infections. Design: Retrospective, ratio‐matched cohort study. Setting: Four acute‐care hospitals within an urban health care system. Patients: A total of 176 hospitalized adults who received definitive ceftaroline (44 patients) or ceftriaxone (132 patients) therapy for at least 7 days between January 2013 and April 2017 for any of the following indications: bone and joint infections (BJI), infective endocarditis (IE), or bloodstream infections (BSI). Measurements and Main Results: The primary outcome was development of neutropenia while receiving cephalosporin therapy, defined as an absolute neutrophil count (ANC) <1500 cells/mm3. Neutropenia severity and patient characteristics were described and compared between the ceftaroline and ceftriaxone groups. The median (interquartile range [IQR]) antibiotic prescription duration was 41 (29–44) days for the ceftaroline group and 40 (28–44) days for the ceftriaxone group (p=0.9). Cephalosporin indications were 112 (64%) BJI, 27 (15%) BSI, 16 (9%) IE, and 21 (12%) multiple infections; ceftaroline was more commonly used in BJI (p=0.03), and ceftriaxone was more commonly used in IE (p=0.01). Neutropenia developed in 16 (9%) patients: 8 (18%) in the ceftaroline group and 8 (6%) in the ceftriaxone group (p=0.03). Median (IQR) onset to neutropenia was 22 (15–28) days, and median (IQR) change in ANC was 2.86 (1.50–4.08) cells/mm3; most cases of neutropenia were mild (12 patients [75%]). The median (IQR) time to mild or moderate‐severe neutropenia was not significantly different (p=0.68): 22 (14–28) and 22 (21–36) days, respectively. Treatment was discontinued in 4 (25%) patients due to neutropenia. Ceftaroline use was independently associated with neutropenia (adjusted odds ratio 3.2, 95% confidence interval 1.2–10.5) after adjusting for lower body mass index strata (18.5–25 kg/m2). Conclusion: Prolonged ceftaroline use was an independent risk factor for developing mild neutropenia. Clinicians should be cognizant of ANC monitoring in scenarios where prolonged ceftaroline courses are prescribed. [ABSTRACT FROM AUTHOR]

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