Its broad antibacterial spectrum qualifies the combination of
piperacillin and
tazobactam for
therapy of nosocomial bacterial central nervous system (
CNS) infections. Since these
infections sometimes are accompanied by only minor dysfunction of the blood-cerebrospinal fluid (CSF) barrier, patients with noninflammatory occlusive
hydrocephalus who had undergone external
ventriculostomy were studied (n = 9; age range, 48 to 75 years). After administration of the first dose of
piperacillin (6 g)-tazobactam (0.5 g) over 30 min intravenously, serum and CSF were drawn repeatedly and analyzed by high-performance liquid chromatography. Pharmacokinetics were determined by noncompartmental analysis. Maximum 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 observed, in median, 1.5 and 2 h after the end of the infusion. Elimination in CSF was considerably slower than in serum (median half-life at beta phase for
piperacillin, 5.9 h in CSF versus 1.47 h in serum; for
tazobactam, 6.1 h versus 1.34 h). For
tazobactam, the ratio of the area under the concentration-time curve (AUC) in CSF to the AUC in serum was approximately three times as high as that for
piperacillin (medians, 0.106 versus 0.034). In view of the
tazobactam concentrations in CSF observed 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 standard dose of 0.5 g three times daily may be necessary for
CNS infections.