Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole

Abstract

Background: AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999-2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period.

A Repurposing Approach Identifies Off-Patent Drugs with Fungicidal Cryptococcal Activity, a Common Structural Chemotype, and Pharmacological Properties Relevant to the Treatment of Cryptococcosis

“…New treatment approaches for cryptococcosis represent an unmet clinical need with significant importance to global health (1,3,5,36). As an approach to the initial development of new anticryptococcal molecules, we designed a screening strategy that would allow us to identify molecules that satisfied some or all of the characteristics described above.…”

Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries

“…Clinical and mycological outcomes in trials of low-dose fl uconazole monotherapy (200-400 mg/day) as induction treatment have been disappointing, with high mortality and prolonged time to CSF sterilisation. 15,63,64 This slow fungal clearance can predispose to development of secondary drug resistance and cryptococcal immune reconstitution syndrome. [65][66][67] Phase 2 studies 30,68 with highdose fl uconazole in com bination with amphotericin B yielded good mycological and clinical outcomes and, in a larger trial, no diff erence in 2 week and 10 week mortality was evident between amphotericin B plus fl uconazole 800 mg/day and amphotericin B plus fl ucytosine.…”

Guidelines for the prevention, diagnosis and management of cryptococcal meningitis and disseminated cryptococcosis in HIV-infected patients

“…The India ink test has good sensitivity (80 -98%) 7,21 and specificity in ARV-naïve and fluconazole-naïve populations, but may have lower sensitivity in patients who are receiving fluconazole for other reasons (commonly mucocutaneous candidiasis), who present early in the course of disease and who have low fungal burden in the CSF. A negative India ink test does not exclude the diagnosis.…”

“…The prognosis of patients with cryptococcal meningitis was very poor prior to the availability of ART, [4][5][6] but present survival rates in the context of ART co-administration are much improved. [7][8][9] Consequently it has become essential to improve the initial acute management of CC in order to maximise the patient's chances of initial survival and subsequent entry into the ART treatment programme.…”