Neutropenia Associated with Long-Term Ceftaroline Use

Abstract

dCeftaroline 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.

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

“…This study found that prolonged ceftaroline exposure is an independent risk factor for developing neutropenia when compared to ceftriaxone; most neutropenia cases were mild and resolved with cessation of the offending β‐lactam. Patients within a lower BMI stratum (i.e., 18.5–25 kg/m 2 ) were also more likely to develop neutropenia, a finding supported by other literature . In most scenarios, ceftaroline was used empirically in culture‐negative infections, which may be suggestive of using a single antibiotic agent to facilitate transitions of care in scenarios where MRSA and Enterobacteriales are suspected.…”

“…However, adverse effects related to ceftaroline use are rarely described. Multiple observational and case report studies have suggested that ceftaroline exposure is associated with higher rates of neutropenia than seemingly listed in the product package insert . The prolonged use of ceftaroline in off‐label, difficult‐to‐treat clinical scenarios may potentiate the risk of neutropenia and contribute to additional patient morbidity and mortality, particularly if adequate follow‐up laboratory monitoring is not performed …”

Early Use of Ceftaroline Fosamil in the United States Veterans Health Care System

“…Two recent studies observed neutropenia in 67 patients when ceftaroline was used ≥2 weeks in duration (10–14% neutropenia) and ≥3 weeks in duration (21% neutropenia) [14]. Another study observed that 18% of their 39 patients experienced neutropenia; patients received ceftaroline for a median of 27 days [15]. Both studies recommended close laboratory monitoring with long-term ceftaroline use.…”

Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

“…Study data were limited to inpatient records; thus, efficacy and safety endpoints reflect short-term data. Notably, neutropenia may be underrepresented, considering that this reaction is known to occur with prolonged ceftaroline administration (33). This analysis included three academic medical centers, and it is unclear if these findings apply to other sites with differing patient populations and practice patterns.…”