title: Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with gram-positive infections.
abstract: Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (Cmin values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ Cmin values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ Cmin values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ Cmin evaluations, were considered. All patients (n=9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ Cmin values during the first week of therapy (9.0±6.4 mg/L vs. 4.9±3.7 mg/L; P<0.01) and thereafter (9.3±5.4 mg/L vs. 4.4±3.4 mg/L; P<0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy.
authors.affiliation: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via G.B. Grassi 74, 20157 Milan, Italy. cattaneo.dario@hsacco.it
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Orlando
authors.forename: Valeria
authors.initials: V
authors.lastname: Cozzi
authors.forename: Laura
authors.initials: L
authors.lastname: Cordier
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Merli
authors.forename: Serena
authors.initials: S
authors.lastname: Fucile
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gulisano
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001773:Blood Cells / Q000187:drug effects*; D016903:Drug Monitoring; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry*; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid