Agranulocytosis with ceftaroline high-dose monotherapy or combination therapy with clindamycin

The only clinically available cephalosporin with in vivo and in vitro activity against methicillin-resistant Staphylococcus aureus is ceftaroline, which is approved for the treatment of soft tissue infection and community-acquired pneumonia in doses of 600 mg intravenously every 12 hours for 2 weeks or less. However, many clinicians use ceftaroline to treat more serious infections and dose more frequently (every 8 hours) for longer periods of time.

A retrospective medication safety assessment was performed at two centers where agranulocytosis was observed in four patients (two at each center) who were treated with ceftaroline. The cases were reviewed by the treating physicians for common features, and the frequency of agranulocytosis was calculated based on the total number of treated patients.

We report four cases of agranulocytosis associated with ceftaroline use, highlighted by prolonged use (more than 14 days) and 8-hour dosing intervals or 12-hour dosing intervals with concomitant clindamycin therapy. When ceftaroline (600 mg every 12 hours) and clindamycin (900 mg every 8 hours) were coadministered for more than 2 weeks, the frequency of agranulocytosis was 18% (2 of 18 patients treated). When ceftaroline alone was administered for more than 2 weeks at 600 mg every 8 hours, agranulocytosis occurred in 5.4% (2 of 37 treated patients). No cases of ceftaroline-related agranulocytosis were seen that did not have these features. In these patients, granulocyte-colony stimulating factor therapy usually resulted in rapid myeloid recovery.

Clinicians should have a heightened awareness of agranulocytosis when using ceftaroline in such settings and monitor complete blood counts at least once/week.