Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB): A Systematic Review to Establish or Revise the Current Recommended Dose for TB Treatment

Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose- and duration-related toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define...

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Veröffentlicht in:Clinical infectious diseases Jg. 67; H. suppl_3; S. S327
Hauptverfasser: Bolhuis, Mathieu S, Akkerman, Onno W, Sturkenboom, Marieke G G, Ghimire, Samiksha, Srivastava, Shashikant, Gumbo, Tawanda, Alffenaar, Jan-Willem C
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 28.11.2018
ISSN:1537-6591, 1537-6591
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Zusammenfassung:Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose- and duration-related toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define the optimal daily dose and dosing frequency of linezolid in MDR-TB regimens. The systematic search resulted in 8 studies that met inclusion criteria. A significant PK variability was observed. Efficacy of linezolid seems to be driven by area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC). Literature is inconclusive about the preferred administration of a daily dose of 600 mg. To prevent development of drug resistance, an AUC/MIC ratio of 100 in the presence of a companion drug at relevant exposure is required. A daily dose of 600 mg seems appropriate to balance between efficacy and toxicity. Being a drug with a very narrow therapeutic window, linezolid treatment may benefit from a more personalized approach, that is, measuring actual MIC values and therapeutic drug monitoring.
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ISSN:1537-6591
1537-6591
DOI:10.1093/cid/ciy625