Alternatives to amphotericin B for Candida rugosa infection

Received 28 August 2003; returned 5 November 2003; revised 18 May 2004; accepted 25 May 2004Objective: Amphotericin B failure is frequently seen in patients with candidaemia caused by Candidarugosa. We evaluated amphotericin B, fluconazole, posaconazole and voriconazole as alternative treat-ments against infection in mice with two isolates of C. rugosa.Methods: Neutropenic mice were inoculated intravenously with C. rugosa. Amphotericin B, flucona-zole, posaconazole and voriconazole were administered for 7 days after infection. Efficacy of the anti-fungal treatment was assessed by survival and tissue burden of C. rugosa.Results: All of the four drugs significantly prolonged survival over controls. With both isolates, kidneycounts were reduced significantly below controls for amphotericin B, fluconazole and posaconazole.However, voriconazole was less effective than the other antifungals.Conclusion: Despite poor clinical response to amphotericin B, in vivo data indicate that amphotericinB increases organ clearance and survival over untreated controls. However, although voriconazoleimproved survival over controls, increased tissue clearance was not seen. This discrepancy may becaused by rapid clearance of voriconazole in mice. These studies suggest fluconazole, posaconazoleor voriconazole may be useful alternatives to amphotericin B in therapy of C. rugosa infection.Keywords: murine model, antifungals, C. rugosa