Assays for therapeutic drug monitoring of β-lactam antibiotics: A structured review.
In some patient groups, including critically ill patients, the pharmacokinetics of β-lactam antibiotics may be profoundly disturbed due to pathophysiological changes in distribution and elimination. Therapeutic drug monitoring (TDM) is a strategy that may help to optimise dosing. The aim of this review was to identify and analyse the published literature on the methods used for β-lactam quantification in TDM programmes. Sixteen reports described methods for the simultaneous determination of three or more β-lactam antibiotics in plasma/serum. Measurement of these antibiotics, due to low frequency of usage relative to some other tests, is generally limited to in-house chromatographic methods coupled to ultraviolet or mass spectrometric detection. Although many published methods state they are fit for TDM, they are inconvenient because of intensive sample preparation and/or long run times. Ideally, methods used for routine TDM should have a short turnaround time (fast run-time and fast sample preparation), a low limit of quantification and a sufficiently high upper limit of quantification. The published assays included a median of 6 analytes [interquartile range (IQR) 4-10], with meropenem and piperacillin being the most frequently measured β-lactam antibiotics. The median run time was 8 min (IQR 5.9-21.3 min). There is also a growing number of methods measuring free concentrations. An assay that measures antibiotics without any sample preparation would be the next step towards real-time monitoring; no such method is currently available.
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium; Department of Critical Care Medicine, Ghent University, Ghent, Belgium. Electronic address: mieke.carlier@ugent.be.
Mieke
M
Carlier
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Veronique
V
Stove
Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia.
Steven C
SC
Wallis
Department of Critical Care Medicine, Ghent University, Ghent, Belgium.
Jan J
JJ
De Waele
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Alain G
AG
Verstraete
Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Jeffrey
J
Lipman
Burns, Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Jason A
JA
Roberts
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000032:analysis*; D001424:Bacterial Infections / Q000188:drug therapy*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D010949:Plasma / Q000737:chemistry; D047090:beta-Lactams / Q000008:administration & dosage* / Q000032:analysis*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams
Chromatography; Free concentrations; Immunoassays; Methods of analysis; TDM; Unbound