Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with Gram-positive infections

Dario Cattaneo, Giovanna Orlando, Valeria Cozzi, Laura Cordier, Sara Baldelli, Stefania Merli, Serena Fucile, Cecilia Gulisano, Giuliano Rizzardini, Emilio Clementi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)586-589
Number of pages4
JournalInternational Journal of Antimicrobial Agents
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Gram-positive infections
  • Haematological toxicity
  • Linezolid
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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