Methods: We performed a retrospective study of ceftaroline-associated neutropenia within a large healthcare system and a comprehensive systematic review of the English literature (2010-2017) of published cases containing individualized case data to describe the incidence, risk factors, and outcomes associated with ceftaroline-associated neutropenia. Neutropenia was defined as an absolute neutrophil count (ANC) of <1500 cells/mm3. Cases with pre-existing neutropenia or other potential reason for the development neutropenia while on ceftaroline were excluded.
Results: A total of 37 cases of ceftaroline-associated neutropenia have been published. The median patient age was 44 years (range 20-90), 22 (59%) were female, and most were receiving ceftaroline for invasive Staphylococcus aureus infections. The median time from ceftaroline initiation to development of neutropenia was at 25 days (range 8-125 days). Agranulocytosis (ANC nadir <100 cells/mm3) developed in 49% of cases (n=18) and an ANC nadir of 0 in 27% (n=10). The median duration of neutropenia was an average of 4 days (range from 1-16 days). Eleven (30%) received granulocyte-colony stimulating factor (G-CSF) treatment and ceftaroline was discontinued in all cases. The outcome was favorable in all cases, and only one case developed a secondary infection during neutropenia. Literature review of studies containing cases and controls (patients receiving drug but did not develop neutropenia) found an incidence of neutropenia of 12% (range 7-18% per individual study) when ceftaroline was utilized for ≥7-14 days, higher than for comparator antibiotics in the literature. Risk factors for the development of neutropenia during ceftaroline varied between studies and remains undefined.
Conclusion: Neutropenia is common when ceftaroline is utilized for ≥14 days and close hematologic monitoring is warranted. Further research is needed to determine the mechanism and risk factors for the high incidence of neutropenia associated with long-term ceftaroline use.
R. B. Turner, None
N. Crum-Cianflone, None