Early mortality during rifampicin-resistant TB treatment

BACKGROUND: Data suggest that treatment with newer TB drugs (linezolid [LZD], bedaquiline [BDQ] and delamanid [DLM]), used in Khayelitsha, South Africa, since 2012, reduces mortality due to rifampicin-resistant TB (RR-TB).METHODS: This was a retrospective cohort study to assess 6-month mortality among RR-TB patients diagnosed between 2008 and 2019.RESULTS: By 6 months, 236/2,008 (12%) patients died; 12% (78/651) among those diagnosed in 2008-2011, and respectively 8% (49/619) and 15% (109/738) with and without LZD/BDQ/DLM in 2012-2019. Multivariable analysis showed a small, non-significant mortality reduction with LZD/BDQ/DLM use compared to the 2008-2011 period (aOR 0.79, 95% CI 0.5-1.2). Inpatient treatment initiation (aOR 3.2, 95% CI 2.4-4.4), fluoroquinolone (FQ) resistance (aOR 2.7, 95% CI 1.8-4.2) and female sex (aOR 1.5, 95% CI 1.1-2.0) were also associated with mortality. When restricted to 2012-2019, use of LZD/BDQ/DLM was associated with lower mortality (aOR 0.58, 95% CI 0.39-0.87).CONCLUSIONS: While LZD/BDQ/DLM reduced 6-month mortality between 2012 and 2019, there was no significant effect overall. These findings may be due to initially restricted LZD/BDQ/DLM use for those with high-level resistance or treatment failure. Additional contributors include increased treatment initiation among individuals who would have otherwise died before treatment due to universal drug susceptibility testing from 2012, an effect that also likely contributed to higher mortality among females (survival through to care-seeking).