Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa

Abstract

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline the non-bedaquiline group (66.2% (45 out of 68) 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% 26.0%; p<0.001) and default (1.5% 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18 out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

Linezolid for drug-resistant pulmonary tuberculosis

“…One of these also recruited from centres in South America, with low tuberculosis burden and mixed MDR‐TB burden (Tiberi 2016). One study was conducted in China (Zhang 2014), another in India (Udwadia 2010), and two in South Africa (Seddon 2014; Olayanju 2018); these three countries have high tuberculosis, tuberculosis/HIV and MDR‐TB burden. Ferlazzo 2018 recruited from Armenia (former Soviet Union country, previously on the high MDR‐TB burden list), India and South Africa.…”

“…Jeong 2015 followed participants until the end of treatment. Guglielmetti 2017 aimed to follow‐up until 24 months after ATT completion, Ferlazzo 2018 until six months from commencement, and Olayanju 2018 reported monthly follow‐up for the duration of hospital stay. Follow‐up duration and frequency were unclear for the remaining studies (Migliori 2009; Udwadia 2010; Jo 2014; Seddon 2014; Kwak 2015; Van Altena 2015; Galli 2016; Jensenius 2016; Tiberi 2016).…”

“…Disaggregated data were available from 12 studies (639 participants), on total number of ‘any' or ‘serious' adverse events or linezolid discontinuation, amongst participants receiving linezolid (Migliori 2009; Jo 2014; Seddon 2014; Zhang 2014; Kwak 2015; Van Altena 2015; Galli 2016; Jensenius 2016; Tiberi 2016; Guglielmetti 2017; Ferlazzo 2018; Olayanju 2018). Six studies (487 participants), provided data for total number of ‘any' or ‘serious' adverse events amongst participants who did not receive linezolid (Seddon 2014; Kwak 2015; Galli 2016; Guglielmetti 2017; Ferlazzo 2018; Olayanju 2018).…”

“…Six studies (487 participants), provided data for total number of ‘any' or ‘serious' adverse events amongst participants who did not receive linezolid (Seddon 2014; Kwak 2015; Galli 2016; Guglielmetti 2017; Ferlazzo 2018; Olayanju 2018). …”

“…Linezolid‐attributed adverse events were reported in a total of 529 participants from 10 studies (Migliori 2009; Udwadia 2010; Jo 2014; Seddon 2014; Zhang 2014; Kwak 2015; Galli 2016; Tiberi 2016; Guglielmetti 2017; Olayanju 2018). These included 108 bone marrow‐related (e.g.…”