Long-term outcome and safety of prolonged bedaquiline treatment for multidrug-resistant tuberculosis

Abstract

Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes. Median bedaquiline treatment duration was 361 days and 33 patients (73%) received prolonged (>190 days) bedaquiline treatment. Overall, 36 patients (80%) had favourable outcome, five were lost to follow-up, three died, and one failed and acquired bedaquiline resistance. No cases of recurrence were reported. Severe and serious adverse events were recorded in 60% and 18% of patients, respectively. Values of Fridericia-corrected QT interval (QTcF) >500 ms were recorded in 11% of patients, but neither arrhythmias nor symptomatic cardiac side-effects occurred. Bedaquiline was discontinued in three patients following QTcF prolongation. No significant differences in outcomes or adverse events rates were observed between patients receiving standard and prolonged bedaquiline treatment.Bedaquiline-containing regimens achieved favourable outcomes in a large proportion of patients. Prolonged bedaquiline treatment was overall well tolerated in this cohort.

Linezolid for drug-resistant pulmonary tuberculosis

“…Three were based in the Republic of Korea; a low tuberculosis burden and low MDR‐TB burden country (Jo 2014; Jeong 2015; Kwak 2015), according to WHO definitions of tuberculosis, tuberculosis/HIV and MDR‐TB burden (WHO 2015b). Four were conducted in low tuberculosis burden and low MDR‐TB burden European countries; Netherlands (Van Altena 2015), Italy (Galli 2016), Norway (Jensenius 2016) and France (Guglielmetti 2017). Two studies recruited from Europe, but also from high MDR‐TB burden former Soviet Union states (Migliori 2009; Tiberi 2016).…”

“…Jensenius 2016 recruited participants of all ages. The remainder, including both RCTs, were conducted in adults (four studies not reporting ages (Migliori 2009; Kwak 2015; Van Altena 2015; Guglielmetti 2017), we assumed to have mostly or exclusively included adults).…”

“…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). …”