Clozapin induzierte Neutropenie und Sepsis

A 44-year-old man with a chronic schizoaffective disorder treated with droperidol 10 mg once daily and clozapine 350 mg at night was transferred to our infectious diseases unit for barrier nursing following a weekly full blood count which revealed neutropenia (white cell count 1.9 x 109/L; neutrophil count 1.24 x 109/L.

Prophylactic itraconazole 400 mg once a night was commenced in addition to granulocyte colony-stimulating factor (G-CSF) 42 MU subcutaneously once daily. Three days later he became febrile, and blood cultures taken 24 hr before the onset of symptoms grew a fully sensitive group G streptococcus and coagulase-negative staphylococcus. Before sensitivities were known, intravenous teicoplanin 200 mg once daily and ceftazidime 2 g three times a day was commenced and his temperature settled. Seven days later he became febrile but he remained clinically well. Repeated examination revealed no localizing signs of infection and repeat cultures were negative. On day 17 he became hypoxic, hypotensive (blood pressure 70/30) and oliguric, though this improved with intravenous rehydration. Intravenous ciprofloxacin and metronidazole were substituted for ceftazidime. The patient was transferred to the intensive care unit.

Intravenous amphotericin was commenced to cover the possibility of fungal infection. In view of the patient’s deteriorating clinical condition, tazobactam 4.5 g three times daily was added to treatment. His G-CSF was changed to granulocyte macrophage colony-stimulating factor (GM-CSF) 80 000 U/kg once daily, as he remained profoundly neutropenic.
On day 29 his neutrophil count returned to normal, although he remained pyrexial and subsequently developed a maculopapular rash. This was thought to be due to a drug reaction, and on cessation of all treatment his temperature and rash resolved. He was transferred back to a psychiatric unit 35 days following admission.
Clozapine-induced neutropenia and granulocytopenia are well-documented complications. The drug manufacturer Sandoz claimed that, over the last 5 years, 48 out of 6316 patients developed agranulocytosis during this period, with two fatalities from uncontrolled sepsis.


Melzer M, Hassanyeh FK, Snow MH, Ong ELC

Clin Microbiol Infect 1998; 4: 604-605





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