Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis

Discontinuation of Linezolid or non-TDM guided dose reduction

Linezolid (LZD) discontinuation for any cause along with non-TDM-guided LZD dose reduction will be assessed. The number of participants who discontinue LZD (defined as an interruption \> 2 weeks in duration), including self-discontinuation by the patient or a decision by the provider to temporarily or permanently discontinue LZD, OR have a non-TDM-guided dose-reduction in response to an adverse event, will be summarized by study arm using basic descriptive statistics.

Evidence of Linezolid Toxicity

Evidence of Linezolid (LZD) toxicity will be evaluated by the number of participants who experience Grade 3 or Grade 4 hematologic (e.g., anemia, thrombocytopenia, neutropenia) or neurologic (e.g., peripheral neuropathy or optic neuritis) adverse events associated with LZD toxicity. LZD-associated Grade 3 or Grade 4 events, documented at any time point up to 6 months, will be summarized by adverse event type and frequency for each study arm.

Unsuccessful final Tuberculosis (TB) end-of-treatment outcome

Unsuccessful final TB treatment outcome is defined as either treatment failure, death, or participant lost to follow-up, as per World Health Organization (WHO) definitions, defined below. End-of-treatment TB outcomes will be captured for all study participants. The number of participants with unsuccessful final TB treatment outcomes will be summarized by study arm using basic descriptive statistics. TB treatment outcomes will be assessed at the end of 6 months of treatment; however, if treatment is extended for any reason, medical records will be reviewed 12 months after treatment initiation to capture a final TB treatment outcome. Treatment failure: The patient's treatment was terminated or they needed to permanently change their regimen due to a lack of response to treatment, adverse drug reaction, or increased drug resistance. Lost to follow-up: The patient stopped taking their medication for two or more months in a row after registering. Death: The patient died

Emergence of new phenotypic resistance to Linezolid

The percentage of participants in each arm who develop phenotypic Linezolid (LZD) resistance will be assessed. Participants who experience treatment failure and remain sputum culture-positive after 4 months, will have a sputum sample collected for additional drug-resistance testing. Results of any isolates which undergo such resistance testing will be reviewed to identify anyone with treatment-emergent linezolid resistance. Additionally, during follow-up visits, participants will be directly assessed for development of LZD resistance. The percentage of participants who develop phenotypic resistance to LZD, as determined by either of these methods, will be summarized by study arm using basic descriptive statistics

TB-free survival

TB-free survival will be assessed by review of each participant's medical record as well as EDRWeb, a South African registry of patients with drug-resistant tuberculosis, to determine whether or not the participant is still alive and free of TB disease. The number/percentage of participants who are alive and free of TB disease will be summarized by study arm.