LAUSR

Background: India has 25% of the world’s tuberculosis. Mumbai is home to 12% of India’s cases that are resistant to rifampin and isoniazid (MDR-TB), but they are often resistant to standard treatment. Linezolid (LZD) resistance is rare, but toxicity limits widespread use. Aim: Describe LZD experience among MDR-TB patients. Methods: From October 2015–November 2016, MDR-TB patients were recruited from a Mumbai chest clinic for a prospective cohort. Medical history and side-effects were evaluated by structured questionnaires. Odds ratios (ORs) and differential time to culture conversion were determined by logistic regressions and t-tests. Results: Of 286 participants, 105 had LZD resistance testing, and 3 (1%) were resistant to LZD. LZD was prescribed to 147 (51.4%) participants, and 112 (76.2%) of those still take LZD. Most received 600mg daily (56.8%) or 300mg daily (37.1%). Mean duration of LZD was 166.3 days (8-722 days), at a mean daily dose of 12.2mg/kg (4.5-26.6mg/kg) and a mean cumulative dose of 102g (7.2–903.6g). 40 participants reported neuropathy (27.3%), which was associated with duration of LZD (OR 1.13/month, p=0.046) but not cumulative dose or dose per kg. Daily dose per kg was associated with a trend towards anemia (OR 1.1 per mg/kg, p=0.124). Participants taking >10mg/kg had higher odds of anemia (OR 2.1, p-0.096). Treatment duration and cumulative dose/kg had small associations with time to culture conversion (R-squared: 0.27, p=0.007 and 0.186, p=0.031, respectively). Higher doses (>10mg/kg or >15mg/kg) were not associated with faster culture conversion. Conclusions: LZD has an increasing role in MDR-TB due to infrequent resistance. Treatment approaches that maximize efficacy and minimize toxicity are urgently needed.