ppi-0903 and Agranulocytosis

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.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Ceftaroline; Cephalosporins; Clindamycin; Drug Therapy, Combination; Female; Fournier Gangrene; Humans; Male; Meningitis, Bacterial; Middle Aged; Retrospective Studies; Staphylococcal Infections; Surgical Wound Infection; Young Adult

A case of profound neutropenia and agranulocytosis associated with the off-label use of ceftaroline is reported.. A 67-year-old Caucasian man arrived at the emergency room with right shoulder pain and weakness that radiated to his right chest, back, and right arm. A review of symptoms was notable for two days of burning with urination associated with decreased urinary output and decreased appetite. Multiple tests revealed the presence of methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis, which was treated with an off-label dosage of ceftaroline (600 mg intravenously every eight hours). At the start of ceftaroline therapy, the patient's baseline absolute neutrophil count (ANC) was 6640 cells/μL and decreased to 816 cells/μL by day 19, eventually falling to 0 cells/μL on day 21 of therapy. Ceftaroline was then discontinued due to the suspicion that the neutropenia was secondary to maturation arrest of the bone marrow. The patient was switched to i.v. daptomycin to finish a six-week course of antibiotics. Interventional radiology placed a drain in the patient's right shoulder during the hospital stay, with symptom improvement. His white blood cell count continued to increase after ceftaroline discontinuation, reaching 6.5×10(3) cells/μL with a differential of 56.6% segmented neutrophils and 28.4% lymphocytes after nine days off of ceftaroline.. A 67-year-old man developed profound neutropenia and agranulocytosis after three weeks of high-dose ceftaroline therapy for the treatment of MRSA septic arthritis. His neutropenia resolved after ceftaroline discontinuation and treatment with an alternative antibiotic.

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Arthritis, Infectious; Ceftaroline; Cephalosporins; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Neutropenia; Off-Label Use