RIFAMPIN CONCENTRATIONS IN VARIOUS COMPARTMENTS OF THE HUMAN BRAIN - A NOVEL METHOD FOR DETERMINING DRUG LEVELS IN THE CEREBRAL EXTRACELLULAR-SPACE

Antimicrobial therapy for brain infections is notoriously difficult be cause of the limited extent of knowledge about drug penetration into t he brain. Therefore, we determined the penetration of rifampin into va rious compartments of the human brain, including the cerebral extracel lular space (CES), Patients undergoing craniotomy for resection of pri mary brain tumors were given a standard dose of 600 mg of rifampin int ravenously before the operation. ri microdialysis probe (10 by 0.5 mm) was inserted into the cortex distantly from the resection and was per fused with two different rifampin solutions. Rifampin concentrations i n the CES were calculated by the no-net-hull method. Intraoperatively, samples were taken from brain tumor tissue, perifocal tissue, and nor mal brain tissue in the case of Dole resections. Rifampin concentratio ns in the various samples were determined by using a bioassay with Sar cinea lutea. In the various compartments, rifampin concentrations were highest within tumors (1.37 +/- 1.34 mu g/ml; n = 8), followed by the perifocal region (0.62 +/- 0.67 mu g/ml; n = 8), the CES (0.32 +/- 0. 11 mu g/ml; n = 6), and normal brain tissue (0.29 +/- 0.15 mu g/ml; n = 7), Rifampin concentrations in brain tumors do not adequately reflec t concentrations in normal brain tissue or in the CES, Rifampin concen trations in the CES, as determined by microdialysis, are the most repr oducible, and the least scattered, of the values for all compartments evaluated, Rifampin concentrations in all compartments exceed the MIC for staphylococci and streptococci, However, CES concentrations may be below the MICs for some mycobacterial strains.