title: Pharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion.
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.
authors.affiliation: Department of General Internal Medicine, University of Bonn, Sigmund-Freud-Strasse 25, Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Buck
authors.forename: Norbert
authors.initials: N
authors.lastname: Bertram
authors.forename: Thomas
authors.initials: T
authors.lastname: Ackermann
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Wilhem Dieter
authors.initials: WD
authors.lastname: Paar
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002761:Cholangitis / Q000188:drug therapy; D017714:Community-Acquired Infections / Q000188:drug therapy; D003428:Cross Infection / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D005335:Fever of Unknown Origin / Q000188:drug therapy; D006760:Hospitalization; D006801:Humans; D007239:Infections / Q000188:drug therapy* / Q000209:etiology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D011014:Pneumonia / Q000188:drug therapy; D011446:Prospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin