Therapeutic drug monitoring (TDM) is an important tool for securing optimal treatment of drugs like beta-lactam antibiotics in hospitalized patients. Developing accurate and robust methods for quantification of the pharmacologically active fraction is needed. A LC-MS/MS assay, using ultrafiltration for selection of the non-protein bound (i.e. pharmacologically active) fraction followed by a 5.5 min chromatographic separation was developed and validated for simultaneous determination of Ampicillin (AMPI), Cefuroxime (CEFU), Meropenem (MERO) and Piperacillin (PIPE)/Tazobactam (TAZO). Inter-batch imprecision was 50% of patients treated with PIPE (and AMPI), and about 30% treated with MERO and CEFU, exhibited beta-lactam levels higher than the local guidelines for maximum recommended levels. Potential toxic levels were found in several patients. We believe that the analytical method developed in this study represents an accurate measure of the pharmacologically active beta-lactam fraction. Evaluation of patient data after one-year use of the method shows higher than expected beta-lactam levels, highlighting the potential benefit of TDM. More studies are needed to determine the clinical significance of TDM in beta-lactam antibiotics.
Christensen et al. (Mon,) studied this question.