Treatment of multidrug-resistant or rifampicin-resistant tuberculosis with an all-oral 9-month regimen containing linezolid or ethionamide in South Africa: A retrospective cohort study.

BACKGROUND: In 2019, the South African tuberculosis program replaced ethionamide with linezolid as a part of an all-oral 9-month regimen. We evaluated treatment outcomes for patients assigned to regimens including linezolid in 2019 and ethionamide in 2017.

METHOD: This retrospective cohort study included patients treated for multi-drug resistant/rifampicin-resistant tuberculosis throughout South Africa between 1 Jan to 31 Dec 2017 and from 1 Jan to 31 Dec 2019. The cohort treated with a 9-month regimen containing ethionamide for four months, was compared with a cohort treated with a 9-month regimen containing linezolid for two months. The regimens were otherwise identical. Inverse probability weighting of propensity scores was used to adjust for potential confounding. A log-binomial regression model was used to estimate adjusted relative risk (aRR) comparing 24-month outcomes between cohorts including treatment success, death, loss to follow up, and treatment failure. Adverse event data were available for the linezolid cohort.

FINDINGS: 817 patients were included in the cohort receiving ethionamide and 4244 in the cohort receiving linezolid. No evidence for a difference was observed between linezolid and ethionamide regimens for treatment success (aRR = 0·96, 95%CI 0·91-1·01), death (aRR = 1·01, 95%CI 0·87-1·17) or treatment failure (aRR = 0·87, 95%CI 0·44-1·75). Loss to follow up was more common in the linezolid group, although estimates were imprecise (aRR = 1·22, 95%CI 0·99-1·50).

INTERPRETATION: No significant differences in treatment success and survival were observed with substitution of linezolid for ethionamide as a part of an all-oral 9-month regimen. Linezolid is an acceptable alternative to ethionamide in this shorter regimen for treatment of multi-drug resistant/rifampicin resistant tuberculosis.