Flucytosine + fluconazole association in the treatment of a murine experimental model of cryptococcosis

Abstract

The efficacy of flucytosine (5-FC) and fluconazole (FLU) association in the treatment of a murine experimental model of cryptococcosis, was evaluated. Seven groups of 10 Balb C mice each, were intraperitoneally inoculated with 10(7) cells of Cryptococcus neoformans. Six groups were allocated to receive 5-FC (300 mg/kg) and FLU (16 mg/kg), either combined and individually, by daily gavage beginning 5 days after the infection, for 2 and 4 weeks. One group received distilled water and was used as control. The evaluation of treatments was based on: survival time; macroscopic examination of brain, lungs, liver and spleen at autopsy; presence of capsulated yeasts in microscopic examination of wet preparations of these organs and cultures of brain homogenate. 5-FC and FLU, individually or combined, significantly prolonged the survival time of the treated animals with respect to the control group (p < 0.01). Animals treated for 4 weeks survived significantly longer than those treated for 2 weeks (p < 0.01). No significant differences between the animals treated with 5-FC and FLU combined or separately were observed in the survival time and morphological parameters. The association of 5-FC and FLU does not seem to be more effective than 5-FC or FLU alone, in the treatment of this experimental model of cryptococcosis.

Invasive fungal infections in solid organ transplant recipients

“…The combination of flucytosine with fluconazole has also produced favourable results, but not as good as the combination with amphotericin B in some studies . The consolidation treatment is usually performed with fluconazole (200–400 mg/day) .…”

The past, present and future of antimycotic combination therapy

“…The combination 5FC+Itra had an additive effect in murine aspergillosis [20]. The combination of 5FC+Keto/Itra was mostly indifferent in murine cryptococcosis, but the combination of 5FC+Flu showed synergism in most studies [30–34] and indifference was only observed in a few experiments [35, 36]. The synergism between 5FC and triazoles was most impressive in murine wangiellosis [20, 25].…”