rifampin and Meningitis--Cryptococcal

The comparison of initial treatment with amphotericin B (0.7 mg/kg/d) plus rifampin (600 mg/d) with amphotericin B (0.7 mg/kg/d) alone for 2 weeks, both followed by fluconazole (400 mg/ d) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS by an open- randomized, controlled, prospective clinical trial is reported. Twenty patients were enrolled in each group. There were no significant differences between the groups in regard to a negative CSF culture for Cryptococcus neoformans in the 2nd and 10th weeks of treatment, time until normal body temperature after treatment, number of patients who died, and persistence of high CSF pressure after completion of treatment. Elevated intracranial pressure was an important factor associated with the patients who died. These results indicate that the combination of amphotericin B plus rifampin is not superior to amphotericin B alone.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; Cryptococcus neoformans; Enzyme Inhibitors; Female; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Prospective Studies; Rifampin

To study the effect of rifampicin on the pharmacokinetics of fluconazole and on clinical outcomes of fluconazole treatment in patients with AIDS-related cryptococcal meningitis.. Forty Thai patients with AIDS and cryptococcal meningitis, of whom 20 had been receiving oral rifampicin for at least 2 weeks to treat tuberculosis.. Patients were treated for cryptococcal meningitis with amphotericin 0.7 mg/kg/day for 14 days followed by fluconazole 400 mg/day, which was reduced to 200 mg/day once culture of cerebrospinal fluid (CSF) became negative. Patients with tuberculosis received oral rifampicin 600 mg/day at night. Blood samples were collected from the first 12 patients in each group and pharmacokinetic parameters for fluconazole were calculated. CSF samples were collected by lumbar puncture and monitored for eradication of Cryptococcus neoformans.. Concomitant administration of rifampicin with fluconazole resulted in significant changes in the pharmacokinetic parameters of fluconazole, including a 39% increase in elimination rate constant, 28% shorter elimination half-life, 22% decrease in area under the concentration-time curve, 17% decrease in maximum concentration and 30% increase in clearance (p < 0.05). Different fluconazole regimens did not affect the extent of change in the elimination rate constant. Although serum concentrations of fluconazole during the time that patients received rifampicin concomitantly with fluconazole 200 mg/day were generally lower than the minimum inhibitory concentration for C. neoformans, there were no significant differences in clinical outcomes between the two groups to date (p = 0.792).. Coadministration of rifampicin with fluconazole caused significant changes in the pharmacokinetic parameters of fluconazole. Long-term monitoring for recurrence rates of cryptococcal meningitis is required to assess the clinical significance of this interaction.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antibiotics, Antitubercular; Antifungal Agents; Area Under Curve; Chromatography, High Pressure Liquid; Cryptococcus neoformans; Drug Interactions; Female; Fluconazole; Half-Life; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Rifampin; Spectrophotometry, Ultraviolet; Tuberculosis

To evaluate the effect of fluconazole on rifampicin pharmacokinetics, eleven AIDS patients received rifampicin (300 mg/day; days 1-28) and fluconazole (400 mg/day; days 15-28). Rifampicin pharmacokinetics were studied on days 14 and 28. There was no significant effect of fluconazole on rifampicin pharmacokinetics. These results suggest that rifampicin dosage adjustment may not be necessary when this drug is coadministered with fluconazole.

Topics: Adult; AIDS-Related Opportunistic Infections; Antibiotics, Antitubercular; Antifungal Agents; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Fluconazole; Humans; Male; Meningitis, Cryptococcal; Middle Aged; Rifampin

The result of initial treatment with amphotericin B (0.7 mg/kg/day) plus rifampin (600 mg/day) for 2 weeks, followed by fluconazole (400 mg/day) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS is reported. There were 10 patients in the study: at 2 weeks, all had made a clinical response and cerebrospinal fluid was sterile in 4 patients; at 10 weeks, all had negative cerebrospinal fluid cultures. Serious side effects were not detected.

Topics: Adult; AIDS-Related Opportunistic Infections; Amphotericin B; Antifungal Agents; DNA-Directed RNA Polymerases; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Male; Meningitis, Cryptococcal; Rifampin