Triple therapy versus amphotericin B plus flucytosine for the treatment of non-HIV- and non-transplant-associated cryptococcal meningitis: retrospective cohort study

Abstract

Objectives Amphotericin B plus flucytosine is the most widely used induction therapy regimen for non-HIV-infected and non-transplant patients; however, the therapeutic outcomes are unsatisfactory, especially when two antifungal drugs are at sub-therapeutic doses. Methods In this study of induction therapy, all non-HIV-infected, non-transplant patients with a first episode of cryptococcal meningitis were divided into two groups. In group I, the patients received amphotericin B plus 5-flucytosine. In group II, in addition to amphotericin B and 5-flucytosine, the patients also received fluconazole. Results In this study, 32 patients were included in group I, and the other 30 were in group II. Although patients from group II had higher fungal burdens with approximately 2100 Cryptococci/ml CSF before treatment, they had a significantly higher frequency of satisfactory outcomes (80% vs. 50%, respectively, P = 0.014). Less time for more patients in group II to have CSF sterilization (P = 0.021; P = 0.046). And more patients in group II had improved neurological function circumstances evaluated by comparing the BMRC staging between patients at discharge and follow-up 10 weeks (P = 0.032). No significant difference was observed in the incidence of adverse events between the two groups. Conclusion Triple therapy a superior alternative induction regimen for patients with non-HIV- and non-transplant-associated cryptococcal meningitis.

Keywords: 5-FC: flucytosine; AmB: amphotericin B; CM:cryptococcal meningitis; CSF: cerebrospinal fluid; Flu: fluconazole; SD: standard deviation; Triple therapy; WBC: white blood cell; clinical outcome; cryptococcal meningitis; fungal clearance.