Therapeutic drug monitoring: linezolid too?

Abstract

Numerous factors interfere with the ability to achieve optimal pharmacokinetic and pharmacodynamic targets and this has been associated with greater mortality and lower cure rates. The recent study by Zoller and colleagues examining linezolid levels in critically ill patients emphasises this point. Their study is unique in the description of the intra-patient and inter-patient variability that occurs and in the degree to which therapy is inadequate; 63% of patients had insufficient levels and only 17% maintained optimal trough values (between 2 and 10 mg/l) throughout the 4 study days. Precisely why this result occurred is uncertain because albumin levels, free linezolid pharmacokinetics and the presence of augmented renal clearance were not recorded in the current study. The extent of this variability makes the case for therapeutic drug monitoring since an area under the inhibitory curve greater than 80 to 120 and the time above the minimum inhibitory concentration over the entire dosing interval strongly correlate with linezolid treatment efficacy. Accordingly, therapeutic drug monitoring where available or, if not available, alternative approaches to drug delivery such as continuous infusion or a dose increase--but particularly the former--may be the answer.