Cerebrospinal Fluid Concentrations of Rifampin in Meningeal Tuberculosis

Abstract Concentrations of rifampin in cerebrospinal fluid were measured after administration of 300 mg of the drug twice daily in 10 patients with probable tuberculous meningitis. The diagnosis was confirmed bacteriologically in only 3 patients. Rifampin was measured in serum and cerebrospinal fluid by a microbiologic assay using a strain of Gaffkya tetragena. Rifampin was present in the cerebrospinal fluid within 2 hours after the drug was first taken in 4 of 10 patients, and at 6 hours, the minimal inhibition concentration for Mycobacterium tuberculosis was exceeded in all patients. The highest concentrations were reached on the second day and subsequently decreased in both serum and cerebrospinal fluid. There was more stability of the concentrations in the cerebrospinal fluid. Rifampin concentrations fluctuated daily in the serum but were stable in the cerebrospinal fluid. Variations in cerebrospinal fluid concentrations among patients were greater than those in serum. All the patients had been treated previously with other antituberculous drugs before therapy with rifampin alone was started, and differing degrees of meningeal inflammation might have contributed to the differences. It was concluded that rifampin can be used in the treatment of meningeal tuberculosis as soon as it is suspected. At this stage of infection, the concentrations of rifampin in the cerebrospinal fluid should approach 20 per cent of the serum concentrations, which represents the fraction of drug in serum that is not protein bound. Despite decline of the concentration in the cerebrospinal fluid in the course of long-term treatment, therapeutic concentrations can be maintained during 1 to 2 months of treatment.