Assays for therapeutic drug monitoring of β-lactam antibiotics: A structured review

•Pharmacokinetics may be severely altered in special patient populations.•Therapeutic drug monitoring might be useful to optimise dosing.•No commercial assays are currently available.•A systematic review was performed of all published methods.

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.