Pharmacokinetics and preliminary safety ofhigh dose linezolid for the treatment of Gram-positive bacterial infections

Lopez-Garcia, Belen, Luque, Sonia, Roberts, Jason A. and Grau, Santiago (2015) Pharmacokinetics and preliminary safety ofhigh dose linezolid for the treatment of Gram-positive bacterial infections. Journal of Infection, 71 5: 604-607. doi:10.1016/j.jinf.2015.06.007


Author Lopez-Garcia, Belen
Luque, Sonia
Roberts, Jason A.
Grau, Santiago
Title Pharmacokinetics and preliminary safety ofhigh dose linezolid for the treatment of Gram-positive bacterial infections
Journal name Journal of Infection   Check publisher's open access policy
ISSN 1532-2742
0163-4453
Publication date 2015-06-19
Sub-type Article (original research)
DOI 10.1016/j.jinf.2015.06.007
Volume 71
Issue 5
Start page 604
End page 607
Total pages 4
Place of publication London, United Kingdom
Publisher W. B. Saunders
Collection year 2016
Language eng
Formatted abstract
Background:  Various pharmacokinetic studies have demonstrated that proposed pharmacodynamic targets for linezolid cannot be achieved in some patients treated with a fixed 600 mg 12-hourly regimen therefore supporting the use of higher than standard doses in these cases. This study aimed to report the pharmacokinetics and preliminary efficacy and safety of 600 mg 8-hourly dosing of linezolid.

Methods:  Observational pharmacokinetic study carried out in patients treated with a higher than standard doses of linezolid, 600 mg 8-hourly, for a proven or suspected infection caused by gram-positive bacteria between February 2013 and July 2014. Linezolid plasma concentrations were analysed using a validated HPLC method. Efficacy, safety and clinical outcomes were assessed.

Results:  Seven patients were included in this data collection and all achieved clinical cure. However, 57.1% of patients manifested haematological toxicity that was associated with trough concentrations exceeding the pre-defined upper limit of 6.3 mg/L (p = 0.047). The other patient that also manifested haematological toxicity had a trough concentration of 6.2 mg/L. The three patients that did not develop toxicity all had trough concentrations <2 mg/L despite the higher linezolid dosing regimen.

Conclusions:  We observed that higher than recommended doses of linezolid may be required in some clinical scenarios, although should only be administered when therapeutic drug monitoring can be performed to avoid high drug exposures that can lead to toxicity.
Keyword Linezolid
High doses
Pharmacokinetics
Critically ill patients
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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