Efficacy of continuous flucytosine infusion against Candida lusitaniae in experimental hematogenous murine candidiasis

Candida lusitaniae may cause life-threatening infections in the immunocompromised host and may be resistant to amphotericin B. Flucytosine (5-FC) is very active against C. lusitaniae isolates in vitro, while the in vivo response of murine infection to 5-FC is not as good. To evaluate the hypothesis that this discrepancy may be primarily due to the short half-life of 5-FC in mice, we compared the same total dosage of 75 mg of 5-FC per kg of body weight per day given by bolus injections or infused continuously via a subcutaneously implanted pump in immunosuppressed CF1 mice infected with C. lusitaniae. The fungal titers in the kidneys of mice treated with the continuous 5-FC infusion were significantly lower (P less than or equal to 0.05) than those in the kidneys of mice that received bolus injections once or thrice daily. The antifungal activity of 5-FC against murine candidiasis is best evaluated when the drug is administered by continuous infusion.