KINETICS OF PIPERACILLIN AND TAZOBACTAM IN VENTRICULAR CEREBROSPINAL-FLUID OF HYDROCEPHALIC PATIENTS

Its broad antibacterial spectrum qualifies the combination of piperaci llin and tazobactam for therapy of nosocomial bacteria) central nervou s system (CNS) infections, Since these infections sometimes are accomp anied by only minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive hydrocephalus who ha d undergone external ventriculostomy were studied (n = 9; age range, 4 8 to 75 years). After administration of the first dose of piperacillin (6 g)-tazobactam (0.5 g) over 30 min intravenously, serum and CSF wer e drawn repeatedly and analyzed by high-performance liquid chromatogra phy. Pharmacokinetics were determined by noncompartmental analysis, Ma ximum concentrations of piperacillin in CSF ranged from 8.67 to <0.37 mg/liter (median, 3.42 mg/liter), and those of tazobactam ranged from 1.37 to 0.11 mg/liter (median, 0.45 mg/liter), CSF maxima were observe d, in median, 1.5 end 2 h after the end of the infusion, Elimination i n CSF was considerably slower than in serum (median half-life at beta phase for piperacillin, 5.9 h in CSF versus 1.37 h in serum; for tazob actam, 6.1 h versus 1.34 h), For tazobactam, the ratio of the area und er the concentration-time curve (AUC) in CSF to the AUC in serum was a pproximately three times as high as that for piperacillin (medians, 0. 106 versus 0.034), In view of the tazobactam concentrations in CSF obs erved in this study, the practice of using a constant concentration of 4 mg of tazobactam per liter for MIC determination is inadequate for intracranial infections, Larger amounts of tazobactam than the standar d dose of 0.5 g three times daily may be necessary for CNS infections.