Ceftaroline-Induced Agranulocytosis

Abstract

LEARNING OBJECTIVE #1: Ceftaroline fosamile is a new fifth generation cephalosporin with broad spectrumbactericidal activity. It is currently approved for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia. We report a case of agranulocytosis as a side effect of ceftaroline use, of which the internist needs to be aware. CASE: A 24-year-old male, intravenous (IV) drug user, presented with right sided chest pain of 3 days duration, associated with productive cough, dyspnea, fatigue, and abdominal pain. Physical exam revealed a heart rate of 143 bpm, and a holosystolic murmur along the left sternal border. Admission complete blood count (CBC) showed a leukocyte count (WBC) of 11.7 K/MM3 with 81 % neutrophils. Chest computer tomography revealed multiple septic pulmonary emboli. Acute coronary syndrome was ruled out with normal cardiac enzymes and non-specific ST changes on EKG. The diagnosis of infective endocarditis was clinched when transthoracic echocardiogram demonstrated tricuspid valve vegetation with severe tricuspid regurgitation and blood cultures grew methicillin resistant staphylococcus aureus (MRSA). The patient's empiric antimicrobials were narrowed to ceftaroline 600 mg IV every 8 h for a planned 6 week course because of cost effectiveness. On ceftaroline day 15, WBC was 8.2 K/MM3 with 82%neutrophils and on day 41, WBC was 0.5 K/MM3 with an absolute neutrophil count of 0. The agranulocytosis was felt to be a side effect of the antibiotic, which was stopped at day 41. The patient's WBC gradually trended upward to 3.3 K/MM3 5 days later and 11.2 K/MM3 8 days after stopping ceftaroline therapy. DISCUSSION: Agranulocytosis is defined as a neutrophil count of <100/microL. It is a rare but serious side effect associated with beta lactam antibiotics use in large doses for longer than 10 days. Cephalosporins have been used >40 % of the time as outpatient IV therapy with associated incidence of leukopenia of <1%but has been historically reported as high as 5-15%with large doses and prolong course. Complete recovery within 1 week after discontinuation of therapy has been observed in most cases. The mechanism is thought to be either from immune mediated cell destruction, or the direct toxic effects on bone marrow. Ceftaroline is recommended for MRSA infections, multidrug resistant strains of streptococcus pneumoniae as well as many gram-negative organisms. It's general side effects include positive coombs test without hemolysis, hypersensitivity and gastrointestinal manifestations. Agranulocytosis has been reported in <1 % of users. In our patient, the high dose, prolong treatment course and the timeline are consistent with ceftaroline associated agranulocytosis. Severe neutropenia and agranulocytosis are rare but reversible side effects of ceftaroline. Monitoring weekly CBC and patient's education about neutropenia symptoms are important aspects of management.