A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis.
AIDS
; 26(11): 1363-70, 2012 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-22526517
ABSTRACT
BACKGROUND:
Cryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500â000 deaths annually. We examined strategies to improve on fluconazole (FLU) monotherapy addition of flucytosine (5-FC) and/or addition of short-course amphotericin B (AmB).METHODS:
In step 1, previously reported, patients were randomized to receive FLU 1200âmg per day with or without 5-FC 100âmg/kg per day for 14 days. In step 2, 43 patients were similarly randomized, with addition of AmB 1âmg/kg per day for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality.RESULTS:
Forty patients (25% with Glasgow Coma Scale <15) were analyzed. EFA for the triple combination arm was greater than that for AmB-FLU -0.50â±â0.15 log CFU/day vs. -0.38â±â0.19 log colony forming units per day (P=0.03); and greater than that for step 1 with FLU-5-FC (-0.28â±â0.17) or FLU alone (-0.11â±â0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, Pâ=â0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, Pâ=â0.1).CONCLUSION:
Addition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival. Both these strategies should be tested in a larger phase III study.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fluconazol
/
Anfotericina B
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Síndrome da Imunodeficiência Adquirida
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Meningite Criptocócica
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Infecções Oportunistas Relacionadas com a AIDS
/
Flucitosina
/
Antifúngicos
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Africa
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article