Granulocytopenia and thrombocytopenia associated with combination therapy of amphotericin B and low-dose flucytosine in a patient with cryptococcal meningitis.

A patient was admitted complaining of fever and headache. He was suspected of meningitis due to nuchal rigidity, and a lumbar puncture was performed. The patient was diagnosed as having cryptococcal meningitis, as Cryptococcus neoformans was found in an India ink preparation of the cerebrospinal fluid. Both amphotericin B and low-dose flucytosine (50 mg/kg/d) were concomitantly administered to the patient and his clinical symptoms improved. However, the combination therapy induced granulocytopenia and thrombocytopenia, which resolved after discontinuance of the drugs. Amphotericin B alone failed to cause granulocytopenia or thrombocytopenia. These results suggest that the mechanisms of granulocytopenia and thrombocytopenia may be toxic reactions to flucytosine in the azotemic state caused by amphotericin B. Our report emphasizes the need for clinicians to monitor for granulocytopenia and thrombocytopenia in patients receiving treatment with both amphotericin B and flucytosine, even when flucytosine is administered in a low dose.