Maintenance Amphotericin B for Cryptococcal Meningitis in the Acquired Immunodeficiency Syndrome (AIDS)

mentioning

confidence: 99%

Use of high-dose fluconazole as salvage therapy for cryptococcal meningitis in patients with AIDS

Berry

Rinaldi

Graybill

1992

“…The infection is usually incurable in AIDS patients, and survivors of the initial infection are treated with lifelong antifungal suppressive therapy (18). Amphotericin B remains the mainstay of therapy for initial treatment of acute infection, and fluconazole therapy is routinely used for chronic suppression to prevent relapses (13).…”

mentioning

confidence: 99%

Sterol compositions and susceptibilities to amphotericin B of environmental Cryptococcus neoformans isolates are changed by murine passage

Currie

Sanati

Ibrahim

et al. 1995

Previous studies have shown that sequential isolates from patients with persistent Cryptococcus neoformans meningoencephalitis can vary in sterol composition and susceptibility to antifungal drugs. To investigate the potential of host factors as mediators of this phenomenon, we compared fungal susceptibilities of environmental and clinical isolates from a limited geographic area. Clinical isolates were less susceptible to amphotericin B than environmental isolates. Five environmental isolates were passaged through BALB/c murine hosts; the passaged isolates had changes in sterol composition and reduced amphotericin B susceptibilities relative to those of the parent isolates. In contrast, murine passage of these isolates did not alter their susceptibilities to fluconazole. The results confirm that changes in sterol composition and antifungal susceptibility can occur in vivo as a result of host factors and suggest that human infection can result in selection of variants with reduced susceptibilities to amphotericin B.

“…Amphotericin B plus flucytosine is generally effective against cryptococcosis of the CNS in most other patient populations (3). However, courses of similar duration of amphotericin B with or without flucytosine in patients with AIDS are frequently associated with recurrent or persistent meningitis (1,11,13,24,25). The hematological toxicity of flucytosine may also preclude its use in patients with AIDS.…”

mentioning

confidence: 99%

“…The current approach to management of cryptococcosis of the CNS in patients with AIDS is an extended and often lifelong course of maintenance therapy. Such an approach has been utilized with amphotericin B and with fluconazole (18,24,25).…”

mentioning

confidence: 99%

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Penetration of SCH-39304, a new antifungal triazole, into cerebrospinal fluid of primates

Walsh

Lester-McCully

Rinaldi

et al. 1990

We characterized the cerebrospinal fluid (CSF) penetration and pharmacokinetics of SCH-39304 in adult rhesus monkeys receiving a single oral dose of SCH-39304 (2.0 mg/kg of body weight). The mean CSF-to-plasma area under the curve ratio was 0.63 (±0.18, standard error of the mean); maximum concentrations were 1.34 pg/mi (±0.18) in CSF and 1.96 pg/ml (±0.43) in plasma. The mean plasma half-life was 45.7 h (±11), and mean CSF half-life was 38.7 h (±3.5). The mean levels of SCH-39304 at 24 h were 1.48 pg/ml (±0.3) in plasma and 0.96 ,g/ml (±0.12) in CSF. We conclude that SCH-39304 effectively penetrates into CSF and achieves concentrations considered active against many opportunistic yeasts and that these concentrations are sustained in CSF for .24 h.