A Review of Therapeutic Drug Monitoring of Beta-Lactams

Abstract

Purpose of Review

Beta-lactam antibiotics are among the most commonly prescribed drug classes in the hospital setting. The pharmacokinetic/pharmacodynamic index correlated with bactericidal activity of beta-lactam antibiotics is the amount of time drug concentrations exceeds the minimum inhibitory concentration over the course of a dosing interval. Standard dosing is based on preclinical trials conducted in healthy volunteers with considerations for renal function and weight to maintain time over minimum inhibitory concentration for an appropriate percentage of the dosing interval. It is commonly accepted that critically ill patients have altered pharmacokinetics which may impact drug efficacy; however, current dosing strategies do not account for these variances. As such, standard dosing delineated in package inserts may not optimize time over the minimum inhibitory concentration. Therapeutic drug monitoring of beta-lactams has been proposed as a possible method to ensure dose optimization in a state of critical illness. To date, there have been limited clinical studies supporting the routine use of therapeutic drug monitoring of beta-lactams, as well as an uncertainty regarding how the process can be applied in the clinical setting. The purpose of this review is to elucidate the current state of therapeutic drug monitoring of beta-lactams and evaluate clinical outcomes of patients who received therapeutic drug monitoring of beta-lactams compared to the standard of care.

Recent Findings

Recent clinical trials suggest there is little demonstrable benefit in patients’ clinical outcomes when therapeutic drug monitoring of beta-lactams is utilized. A number of studies have been performed with variable trial designs. In these studies, there are different pharmacokinetic/pharmacodynamic targets, pathogens, beta-lactams, and primary outcomes. This makes assessment of therapeutic drug monitoring challenging.

Summary

Therapeutic drug monitoring of beta-lactam antibiotics is limited by lack of compelling clinical evidence demonstrating benefit in patient outcomes. Challenges in clinical trial design make patient selection difficult and may underestimate the impact of therapeutic drug monitoring. Widespread availability of assays with on-site testing and validated monitoring software would allow for use in select patients with unpredictable pharmacokinetics.