The Role of Fluconazole in the Treatment of Candida Endocarditis: A Meta-Analysis

The treatment of Candida infective endocarditis generally involves infected valve removal accompanied by antifungal therapy with amphotericin B or a lipid-based derivative, with or without flucytosine. While often used as chronic suppressive therapy in these patients, the precise role for fluconazole has not been established. We conducted a meta-analysis of 64 literature cases of Candida endocarditis whose management did not include valve replacement but who received fluconazole, alone or concurrently or in sequence with 1 or more other antifungal drugs.Forty-nine (77%) patients were cured (n = 44) or improved (n = 5), 4 relapsed (6%), and 11 failed (10 of whom died) (17%). Among 19 patients for whom fluconazole was administered as the sole antifungal therapy, 11 (58%) were cured or improved. In contrast, among 45 patients who received 1 or more other antifungal agents in addition to fluconazole, 38 (84%) were cured or improved (p = 0.02). Eighteen of 21 (86%) patients with native valve infection were cured or improved compared with 13 of 19 (68%) patients with prosthetic valve endocarditis (p = 0.13). The mean duration of successful fluconazole regimens was 134 days. Twenty of 21 (95%) patients who received fluconazole as chronic suppressive therapy for ≥6 months were cured. Prognosis was independent of Candida species or patient age. Among 23 historical controls managed with fluconazole-containing antifungal therapy plus valvular surgery, survival was 91%.In conclusion, fluconazole-containing, combination antifungal therapy, with or without concomitant valve replacement, and followed by prolonged, perhaps indefinite fluconazole suppression, is effective in patients with Candida endocarditis.