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

Bolhuis, M. S., Akkerman, O. W., Sturkenboom, M. G. G., Ghimire, S., Srivastava, S., Gumbo, T. & Alffenaar, J-W. C., 15-Dec-2018, In : Clinical Infectious Diseases. 67, suppl_3, p. S327-S335 9 p.

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  • Linezolid-based Regimens for Multidrug-resistant Tuberculosis (TB)

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DOI

Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose-and durationrelated 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.

Original languageEnglish
Pages (from-to)S327-S335
Number of pages9
JournalClinical Infectious Diseases
Volume67
Issue numbersuppl_3
Publication statusPublished - 15-Dec-2018

    Keywords

  • pharmacokinetics/pharmacodynamics, optimal dose, Monte Carlo simulation, probability of target attainment, EARLY BACTERICIDAL ACTIVITY, HOLLOW-FIBER MODEL, PHARMACOKINETICS-PHARMACODYNAMICS, MOXIFLOXACIN, CHILDREN, CLARITHROMYCIN, OXAZOLIDINONES, FAROPENEM, EFFICACY, THERAPY

ID: 71529905