Treatment of Cryptococcal Meningitis with Combination Amphotericin B and Flucytosine for Four as Compared with Six Weeks

Abstract

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent--whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P less than 0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy.

Fatores prognósticos da meningoencefalite criptocócica

“…A diminuição do nível de consciência tem sido descrita como preditora de letalidade em diversas encefalites infecciosas 10,13,18,19 . Acreditamos que este dado traduza maior agressão encefálica que muitas vezes está associada a hipertensão intracraniana, vasculite e alterações eletrolíticas.…”

Disseminated Cryptococcosis Presenting with Adrenal Insufficiency and Meningitis: Resistant to Prolonged Antifungal Therapy but Responding to Bilateral Adrenalectomy.

“…The CSF cell count and the cryptococcal antigen titers of CSF and serum did not normalize either. It was reported that serum and CSF titers of >1:8 at one month or more after treatment in patients with cryptococcosis are associated with relapse (18). However, two weeks after bilateral adrenalectomy, the CSF cell count decreased to the normal range and the CSF and serum cryptococcal antigen titers became negative in the present patient.…”

“…However, the survivors showed a good response to antifungal therapy (1,3). Intravenous amphotericin B with or without flueytosine, is usually the standard form of therapy (18). Recently, an increasing number of reports have been published concerning AIDS-associated cryptococcal meningitis (9)(10)(11)(12)(19)(20)(21)(22).…”

Combination antifungal therapy: what can and should we expect?

“…4 weeks). 22 However, with the advent of HIV infection and its severe immunosuppression, a new strategy was adopted, which included induction, clearance and suppression phases of treatment. In the initial induction phase, it was found that the combination of amphotericin B plus flucytosine reproducibly reduced CSF yeast counts over 2 weeks of treatment and also reduced the numbers of relapse cases.…”