A Comparison of Amphotericin B Alone and Combined with Flucytosine in the Treatment of Cryptoccal Meningitis

Abstract

We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.

Epidemiology and Clinical Characteristics of Cryptococcal Meningitis in China (1981-2013): A Review of the Literature

“…Treatment with AmB+FCZ+5FC trigeminy is most effective. As for the treatment of HIVassociated cryptococcal meningitis, it consists of three phases: induction, consolidation, and maintenance [21]. Although later relapse is unlikely to occur during successful ART (antiretroviral therapy), lifelong fluconazole is still recommended after the presence of cryptococcal meningitis [22,23].…”

Treatment of invasive fungal infections in cancer patients—Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…However, an infection may occur along with T-cell defects or following a CD4-lymphocyte-depleting therapy. D-AmB (0.7-1 mg/kg) plus 5-flucytosine (100 mg/kg) for 2 weeks followed by maintenance therapy with fluconazole 400 mg/ day for 10 weeks is the recommended antifungal treatment of cryptococcal meningitis in HIV-infected patients (see Table 4) (AI) [5,8,38,84,95]. Data about AmB lipid formulations are limited.…”

Cryptococcosis in apparently immune-competent patients: taxonomy, epidemiology, pathophysiology and treatment

“…35 This approach to treatment is based on two early clinical trials in a heterogeneous group of patients with meningitis who were neither HIV-infected nor transplant recipients: the first trial documented the superiority of a combination low-dose amphotericin B and high-dose flucytosine regimen vs low-dose amphotericin B alone; and, the second, the superiority of a 6-week vs 4-week combination regimen. 36,37 These trials were published prior to the availability of triazole agents and adoption of the standard 3-phase regimen with a high-dose amphotericin B and flucytosine backbone. Thus, the IDSA recommendations have been modified to include currently-accepted doses of amphotericin B deoxycholate and flucytosine and consolidation/ maintenance phases of treatment to reduce the risk of relapse.…”