Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy

Clin Infect Dis. 2007 Feb 1;44(3):357-63. doi: 10.1086/510590. Epub 2007 Jan 2.

Abstract

Background: Piperacillin-tazobactam is frequently used to treat Pseudomonas aeruginosa infections in critically ill patients. In an effort to improve clinical outcomes, an extended-infusion dosing scheme for piperacillin-tazobactam therapy was devised using a Monte Carlo simulation and was adopted into clinical practice at Albany Medical Center (Albany, New York). This study evaluates the clinical implications of extended infusion of piperacillin-tazobactam therapy for critically ill patients with P. aeruginosa infection.

Methods: We performed a cohort study of patients who received piperacillin-tazobactam therapy for a P. aeruginosa infection that was susceptible to piperacillin-tazobactam during the period January 2000-June 2004. Prior to February 2002, all patients received intermittent infusions of piperacillin-tazobactam (3.375 g intravenously for 30 min every 4 or 6 h); after this time, all patients received extended infusions of piperacillin-tazobactam (3.375 g intravenously for 4 h every 8 h). Data on demographic characteristics, disease severity, and microbiology were collected, and outcomes were compared between groups.

Results: A total of 194 patients comprised the 2 study groups: 102 patients received extended infusions of piperacillin-tazobactam, and 92 patients received intermittent infusions of piperacillin-tazobactam. No differences in baseline clinical characteristics were noted between the 2 groups. Among patients with Acute Physiological and Chronic Health Evaluation-II scores > or =17, 14-day mortality rate was significantly lower among patients who received extended-infusion therapy than among patients who received intermittent-infusion therapy (12.2% vs. 31.6%, respectively; P=.04), and median duration of hospital stay after collection of samples for culture was significantly shorter for patients who received extended-infusion therapy than for patients who received intermittent-infusion therapy (21 days vs. 38 days; P=.02).Conclusions. These results indicate that extended-infusion piperacillin-tazobactam therapy is a suitable alternative to intermittent-infusion piperacillin-tazobactam therapy, and they strongly suggest that improved outcomes may be realized by administering extended-infusion piperacillin-tazobactam therapy to critically ill patients with P. aeruginosa infection.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • APACHE
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Cohort Studies
  • Critical Illness
  • Cross Infection / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous / methods
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Models, Biological
  • Monte Carlo Method
  • Penicillanic Acid / administration & dosage
  • Penicillanic Acid / analogs & derivatives
  • Piperacillin / administration & dosage
  • Piperacillin, Tazobactam Drug Combination
  • Pseudomonas Infections / drug therapy*
  • Retrospective Studies
  • beta-Lactams / pharmacokinetics

Substances

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