Therapeutic drug management of linezolid: a missed opportunity for clinicians?

- 6 years of linezolid TDM in a routine clinical setting is described.
- 20-fold interindividual variability in linezolid plasma trough concentrations is observed.
- Positive significant correlations between linezolid trough concentrations and patient age or renal function were found.
- Progressive increase in linezolid concentrations with time observed in patients with more than one TDM assessment.
- Despite observed increase in linezolid concentrations, most physicians did not change the dose according to TDM results.

Some studies have shown that adjustments to the linezolid dose guided by therapeutic drug monitoring (TDM) can reduce interindividual variability in drug exposure and improve linezolid tolerability. In this study, 6 years of linezolid TDM, a diagnostic service for our hospital and others in the Milan (Italy) area, is described. Samples were collected immediately before the morning dose intake (trough concentrations) in steady-state conditions. Linezolid concentrations were quantified by a validated high-performance liquid chromatography (HPLC) method. Four hundred linezolid trough concentrations from 220 patients were collected. A 20-fold variability in linezolid levels was observed. Positive and significant correlations between linezolid trough concentrations and patient age (r = 0.325, P <0.01) or serum creatinine (r = 0.511, P <0.01) were found. A progressive increase in linezolid concentrations with time was observed in a subgroup of patients with more than one TDM assessment. Elderly patients, especially those aged >80 years and with impaired renal function, are at a higher risk of overexposure to linezolid. Despite the observed progressive increase in linezolid concentrations over time, most physicians did not change the drug dose according to the TDM results, even in the presence of frank overexposure to linezolid.