title: Variability of piperacillin concentrations in relation to tazobactam concentrations in critically ill patients.
abstract: Therapeutic drug monitoring for critically ill patients receiving piperacillin/tazobactam is described as a useful tool. However, the minimum inhibitory concentration of piperacillin depends on a sufficiently high concentration of tazobactam in case of β-lactamase-producing strains. Therefore, the relationship between piperacillin and tazobactam concentrations was assessed in a heterogeneous group of critically ill patients. Sixty patients with severe infections receiving 4.5 g of piperacillin/tazobactam 2-3 times daily by intermittent infusion were included in this prospective observational study (NCT01793012). Over 4 days, multiple serum samples were obtained to determine the total piperacillin and tazobactam concentrations. The target ranges were defined as trough levels >16 mg/L (>22.5 mg/L) and >4 mg/L (>5.7 mg/L) for the calculated unbound concentrations (measured total concentrations) of piperacillin and tazobactam, respectively. Despite a high correlation coefficient (r = 0.93) comparing piperacillin and tazobactam trough levels, the piperacillin/tazobactam quotients varied between ca. 1 and 10. From linear regression analysis of piperacillin versus tazobactam values, it follows that a piperacillin trough level of 22.5 mg/L might be associated with tazobactam trough levels ranging from 1.5 mg/L to 10.1 mg/L. A 70 mg/L threshold for total piperacillin trough levels would be necessary to ensure that tazobactam concentrations are >5.7 mg/L. Because of the observed variability of piperacillin/tazobactam quotients, defining the total piperacillin target range ≥70 mg/L might be useful to ensure that tazobactam concentrations do not fall below 5.7 mg/L. Further studies are necessary to confirm that the used therapeutic ranges are associated with optimal outcomes in critically ill patients.
authors.affiliation: Institute of Laboratory Medicine, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zander
authors.affiliation: Department of Anesthesiology, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Gundula
authors.initials: G
authors.lastname: Döbbeler
authors.affiliation: Institute of Laboratory Medicine, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.affiliation: Department of Anesthesiology, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Scharf
authors.affiliation: Institute of Laboratory Medicine, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Mikayil
authors.initials: M
authors.lastname: Huseyn-Zada
authors.affiliation: Max von Pettenkofer-Institute, Ludwig-Maximilians-University of Munich, Marchioninistrasse 17, 81377 Munich, Germany.
authors.forename: Jette
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Anesthesiology, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Frey
authors.affiliation: Institute of Laboratory Medicine, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
authors.affiliation: Department of Anesthesiology, Hospital of the Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. Electronic address: Michael.Zoller@med.uni-muenchen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Zoller
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016638:Critical Illness; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies; D044967:Serum / Q000737:chemistry*; D065093:beta-Lactamase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin
keywords: Antibiotics; Intensive care unit; Pharmacokinetics; Target range; Therapeutic drug monitoring