Abstract

Therapeutic Drug Monitoring of Linezolid

Michael Vogeser, Professor, University of Munich

Linezolid is an important antibiotic for the treatment of severe infections in critically ill patients when caused by Gram-positive strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Substantial heterogeneity in pharmacokinetic variables, however, is observed in this patient group, leading to a high incidence of sub-therapeutic serum concentrations when standard dosing regimens are applied. LC-MS/MS methods enable personalized linezolid treatment based on therapeutic drug monitoring. Goal of this therapeutic individualisation is to ensure that serum linezolid concentrations remain continuously above the minimal inhibitory concentration against most bacteria from relevant species. Since no methods for linezolid quantification are available on standard laboratory platforms it is useful to implement LC-MS/MS for this aim. Applying isotope dilution internal standardisation and semi-automated sample preparation using on-line solid phase extraction, very reliable and convenient methods can be implemented for routine therapeutic drug monitoring of linezolid. The analyte is exemplary for emerging analytes of high clinical value which are so far not addressed by diagnostic companies, and for which mass spectrometry application in the clinical laboratory opens important perspectives for optimized therapy.