Neutropenia Associated with Long-Term Ceftaroline Use

Abstract

Ceftaroline is a fifth-generation cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Neutropenia is a rare serious adverse event for the class of cephalosporins; however, we observed several cases of severe neutropenia in our outpatient infectious disease practice believed to be associated with ceftaroline use. The aim of this study was to determine the incidence of neutropenia among patients receiving ceftaroline therapy for more than 7 days. We conducted a retrospective cohort analysis of patients admitted to an 800-bed regional medical center between June 2012 and December 2014 who received ceftaroline for more than 7 days to assess the incidence of developing clinically significant neutropenia. Demographic and patient care data points as well as underlying admitting and chronic diagnoses were retrospectively collected from the medical record. Clinically significant neutropenia was defined as an absolute neutrophil count (ANC) less than 1,500 cells/mm(3). Analysis was performed to determine the incidence, severity, and outcome of neutropenia following ceftaroline administration. A total of 39 patients were included in the cohort. The median duration of therapy was 27 days. Seven patients (18%) developed neutropenia while on ceftaroline therapy. Four (10%) of the neutropenic patients had an ANC of <500 cells/mm(3). The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm(3) on day 24. We determined that extended ceftaroline infusion is associated with the development of neutropenia. We recommend obtaining a complete blood count (CBC) with differential at the onset of therapy and weekly thereafter. Should the ANC fall below 2,500 cells/mm(3), then twice-weekly CBCs should be monitored for the duration of ceftaroline therapy, and therapy should be discontinued if the ANC falls to 1,500 cells/mm(3) or less.

FIG 1

Box plot of duration of therapy in those who became neutropenic and those who did not. P = 0.755.

FIG 2

Graphs of mean hemoglobin concentration (A), mean eosinophil count (B), mean lymphocyte count (C), and mean platelet count (D) by week in patients who did and did not become neutropenic through the course of therapy.

FIG 3

Graph of mean absolute neutrophil count (ANC) by week in those who became neutropenic and those who did not. CI, confidence interval.