title: Therapeutic drug management of linezolid: a missed opportunity for clinicians?
abstract: 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.
authors: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via Giovanni Battista Grassi 74, 20157 Milan, Italy. Electronic address: dario.cattaneo@asst-fbf-sacco.it.
authors: Dario
authors: D
authors: Cattaneo
authors: Department of Infectious Diseases, L. Sacco University Hospital, Milan, Italy.
authors: Cristina
authors: C
authors: Gervasoni
authors: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via Giovanni Battista Grassi 74, 20157 Milan, Italy.
authors: Valeria
authors: V
authors: Cozzi
authors: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via Giovanni Battista Grassi 74, 20157 Milan, Italy.
authors: Simone
authors: S
authors: Castoldi
authors: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via Giovanni Battista Grassi 74, 20157 Milan, Italy.
authors: Sara
authors: S
authors: Baldelli
authors: Clinical Pharmacology Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università degli Studi di Milano, Milan, Italy; E. Medea Scientific Institute, Bosisio Parini, Italy.
authors: Emilio
authors: E
authors: Clementi
mesh_terms: D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods* / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007558:Italy; D000069349:Linezolid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid
keywords: Bacterial infection; Interindividual variability; Linezolid; Pharmacokinetics; Therapeutic drug monitoring