The efficacy of fluconazole (Diflucan) 600 mg/day versus itraconazole (Sporanox) 600 mg/day for treatment of cryptococcal meningitis in AIDS patients

Cryptococcal meningitis, a life-threatening infection caused by cryptococcus neoformans, is one of the major opportunistic infections that affect people with AIDS. The results of treatment, when following current dosing recommendations, are still unsatisfactory, according to the authors of this report.

The objective of the current study was to evaluate higher than recommended doses of oral fluconazole (Diflucan) and itraconazole (Sporanox) as primary therapy for cryptococcal meningitis in AIDS patients.

HIV positive patients with primary cryptococcal meningitis, who had been treated initially with amphotericin B for two weeks were included in this study. They were randomised into two groups: (1) to receive either fluconazole 600 mg daily or (2) to receive itraconazole 600 mg daily for 10 weeks. The response to the two different regimens was defined as successful if after 10 weeks of treatment no clinical symptoms and signs of meningitis remained and the cerebrospinal fluid (CSF) fungal culture was negative.

The trial was performed from April 1999 to April 2000 at Srinagarind Hospital, Khon Kaen, Thailand. Of the 35 patients who proved for the final evaluation of the study, 19 cases were assigned to the fluconazole regimen and 16 to the itraconazole group.

Ten weeks after treatment, all patients recovered completely. The CSF sterilisation rate for the fluconazole group and for the itraconazole group were 100% and 94%, respectively.

The results of this study indicate that treatment with either 600 mg/day of fluconazole or itraconazole as primary treatment have the same efficacy for AIDS patients with cryptococcal meningitis.

According to the study authors: “The results of this study also suggest that treatment with the higher doses (600mg/day vs 200mg/day) may be superior to treatment regimens using lower doses, as can be judged from the clinical outcome and the results of the mycological cultures.”

P Mootsikapun et al. The efficacy of fluconazole 600 mg/day versus itraconazole 600 mg/day as consolidation therapy of cryptococcal meningitis in AIDS patients. Journal of the Medical Association Thailand 86(4): 293-298. April 2003.

Comment

The landmark study that has defined the current standard of care for cryptococcal meningitis was published by the ACTG and the Mycoses Study group in 1997 (van der Horst C et al. NEJM 1997; 337: 15-21). This established the efficacy of induction therapy with intravenous amphotericin B and flucytosine followed by ten weeks of oral fluconazole (400 mg/day). In that study fluconazole maintenance therapy was superior to itraconazole (400 mg/day) in terms of CSF sterilisation (72% vs. 60%, p=0.05).

This study uses higher doses of maintanence oral fluconazole and itraconazole (600 mg/day), and although the numbers are small, suggests equivalent rates of CSF sterilisation. Itraconazole has poor CSF penetration and an unpredictable oral bioavailability, and careful attention to potential toxicity, drug interactions and serum levels are required. Intravenous induction therapy with amphotericin and flucytosine for the first two weeks is still required.

However, voriconazole, a new azole anti-fingal agent with proven efficacy against invasive aspergilliosis (as compared to amphotericin), has activity against cryptococcal species and good CNS penetration and may be the oral agent of choice in the future.