title: Rapid quantification of six β-lactams to optimize dosage regimens in severely septic patients.
abstract: A fast analytical procedure was developed for the simultaneous quantification of cefepime (CEF), meropenem (MEM), ceftazidime (CZA), cefuroxime (CFX), aztreonam (AZT), and piperacillin (PIP) in serum of intensive care patients. The β-lactam pharmacokinetic parameters can be altered in severe sepsis due to changes in the distribution, the metabolism and the elimination process. Therapeutic drug monitoring (TDM) of β-lactams is therefore recommended in critically ill patients. The plasma samples were spiked with cefoperazone as internal standard and proteins were precipitated with methanol. The different β-lactams were separated with high performance liquid chromatography within 18 min, and quantified by UV spectrophotometry with a diode array detector. The method was validated by means of the accuracy profile approach based on β expectation tolerance intervals. The acceptance limits were settled at ± 30% according to the regulatory requirements. Assay validation demonstrated good performance for all β-lactams analyzed in terms of trueness, repeatability, linearity and intermediate precision over the range of 2-200 μg/mL. The simple extraction procedure provides respective absolute and relative recoveries ranging from 70% to 86% and from 66% to 89% for all the β-lactams analyzed. Few interferences were observed and the method was easily applicable to TDM in intensive care patients. The quantification of β-lactams should allow for antibiotic regimen adjustment in critically ill patients.
authors.affiliation: Laboratory of Clinical Chemistry, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. fleur.wolff@erasme.ulb.ac.be
authors.forename: Fleur
authors.initials: F
authors.lastname: Wolff
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deprez
authors.forename: Lucie
authors.initials: L
authors.lastname: Seyler
authors.forename: Fabio
authors.initials: F
authors.lastname: Taccone
authors.forename: Maya
authors.initials: M
authors.lastname: Hites
authors.forename: Béatrice
authors.initials: B
authors.lastname: Gulbis
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cotton
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D006801:Humans; D007362:Intensive Care Units; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution; D047090:beta-Lactams / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams