Pharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion

Int J Antimicrob Agents. 2005 Jan;25(1):62-7. doi: 10.1016/j.ijantimicag.2004.08.012.

Abstract

In the present study 24 hospitalized patients requiring empirical antibiotic treatment were randomly assigned to receive the beta-lactam antibiotic/beta-lactamase inhibitor combination piperacillin-tazobactam either as an intermittent or as a continuous infusion. According to pharmacokinetic modelling, the daily dose was reduced by 33% in patients receiving continuous infusion compared with intermittent infusion. Dose reduction because of impaired renal function was required in the intermittent dosing group for 5 of 12 patients compared with 1 of 12 patients in the continuous infusion group. However, the mean daily dose in the continuous group was 15% less than the intermittent infusion group. Mean serum concentrations of piperacillin were to 39.0 microg/ml after the end of bolus distribution, exceeding by far the minimal inhibitory concentration of the most clinically relevant pathogens. The corresponding mean value for tazobactam was 6.3 microg/ml. Pharmacokinetic/pharmacodynamic modelling suggests that both treatment schemes should produce virtually identical anti-infective responses to sensitive, intermediate and resistant strains. In the present study the continuous infusion of piperacillin/tazobactam provided adequate antibacterial activity over the 24-h dosing period and offers the potential for a substantial reduction in the total daily dose.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use
  • Cholangitis / drug therapy
  • Community-Acquired Infections / drug therapy
  • Cross Infection / drug therapy
  • Drug Administration Schedule
  • Female
  • Fever of Unknown Origin / drug therapy
  • Hospitalization
  • Humans
  • Infections / drug therapy*
  • Infections / etiology
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Penicillanic Acid / administration & dosage*
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacokinetics*
  • Penicillanic Acid / therapeutic use
  • Piperacillin / administration & dosage*
  • Piperacillin / pharmacokinetics*
  • Piperacillin / therapeutic use
  • Piperacillin, Tazobactam Drug Combination
  • Pneumonia / drug therapy
  • Prospective Studies
  • Treatment Outcome
  • Urinary Tract Infections / drug therapy

Substances

  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Piperacillin