Clinical Pharmacology of Piperacillin/Tazobactam

Abstract

Piperacillin extends the spectrum of activity of ampicillin to include most strains of Pseudomonas aeruginosa, Enterobacteriaceae (non-β-lactamase-producing), many Bacteroides species, and Escherichia faecalis. Combined with the β-lactamase inhibitor tazobactam, piperacillin/tazobactam has the broadest antibacterial spectrum of penicillins including activity against methicillin-susceptible Streptococcus aureus, Haemophilus influenzae, Bacillus fragilis, most Escherichia coli, and Klebsiella. Piperacillin is only available for parenteral administration. Piperacillin is an important agent for treatment of patients with serious infections caused by gram-negative bacteria including bacteraemias, pneumonias, infections following burns, and urinary-tract infections owing to microorganisms resistant to ampicillin and the bacteria responsible include Pseudomonas aeruginosa, indole-positive strains of Proteus, and Enterobacter species. The efficacy and safely of piperacillin/tazobactam have been reviewed and piperacillin and tazobactam concentrate in tissues in significant amounts. The elimination half-life of piperacillin and tazobactam is about 1 and 1.8 hours, respectively. The prophylaxis, treatment, and trials with piperacillin/tazobactam have been reviewed. Piperacillin/tazobactam may induce nephrotoxicity or neutropenia in some patients. The penetration of piperacillin into the central nervous system is good but tazobactam reaches concentrations in the cerebrospinal fluid inadequate to protect piperacillin by organisms producing β-lactamases and piperacillin/tazobactam treats bacterial meningitis. Piperacillin and tazobactam freely cross the human placenta. The aim of this study is to review piperacillin/ tazobactam efficacy and safely, prophylaxis, treatment, trials, treatment of meningitis, and piperacillin and tazobactam pharmacokinetics, penetration into the body-tissues and into the cerebrospinal fluid, transfer across the human placenta, and metabolism of piperacillin.