Reply to Kim et al., “Optimal Dose or Optimal Exposure? Consideration for Linezolid in Tuberculosis Treatment”

REPLY

We thank Kim and colleagues for their interest in our study (1, 2). We could not agree more that prevention of linezolid toxicity, potentially by therapeutic drug monitoring (TDM) as suggested, is likely to improve patient safety and treatment outcomes when linezolid is used in a regimen to treat TB (3). There is an urgent need to validate the proposed area under the concentration-time curve (AUC)/MIC ratio of >100, following a hypothesis generated in the hollow-fiber system, in a clinical setting. Trials are needed to provide data on the value and successful outcomes of therapeutic drug monitoring for linezolid and to determine if such monitoring is feasible in countries with high TB burdens.

We would like to point out we did not intend to recommend that a linezolid dosage of 1,200 mg daily is required for efficacy in a regimen. The conclusion drawn from our study is that 1,200 mg daily is safe and can contribute solidly to the bactericidal activity of a regimen in the first 2 weeks of treatment. Once the rapid initial reduction of the bacterial burden has been achieved, lower dosage or even discontinuation of linezolid might be considered to reduce or avoid toxicity without compromising regimen efficacy. The Global Alliance for Tuberculosis Drug Development is currently testing this concept of higher versus lower doses and shorter versus longer durations of linezolid in a 6-month regimen for highly drug-resistant tuberculosis (ClinicalTrials registration no. NCT03086486). Results from this study can be expected in 2022.