Impact of bedaquiline on treatment outcomes of multidrug-resistant tuberculosis in a high-burden country

Abstract

Evaluation of novel anti-tuberculosis (TB) medicines for the treatment of multidrug-resistant (MDR)-TB continues to be of high interest on the TB research agenda. We assessed treatment outcomes in patients with pulmonary MDR-TB who received bedaquiline containing treatment regimens in the Republic of Moldova, a high-burden country of MDR-TB.MethodWe systematically analysed the “SIMETB” national electronic TB database in the Republic of Moldova and performed a retrospective propensity score matched comparison of treatment outcomes in a cohort of patients with MDR-TB who started treatment during 2016–2018 with a bedaquiline-containing regimen (bedaquiline cohort) and a cohort of patients treated without bedaquiline (non-bedaquiline cohort).ResultsFollowing propensity score matching, 114 patients were assigned to each cohort of MDR-TB patients. Patients in the bedaquiline cohort had a higher 6 month sputum culture conversion rate than those in the non-bedaquiline cohort, (66.7% versus 40.3%, p<0.001). Patients under bedaquiline containing regimens had a higher cure rate assessed by both WHO and TBNET definitions (55.3% versus 24.6%, p=0.001 and 43.5% versus 19.6% p=0.004, correspondingly), as well, a lower mortality rate (8.8% versus 20.2%, p<0.001, by WHO and 10.9% versus 25.2%, p=0.01, by TBNET). In patients who previously failed on MDR-TB treatment, more than 40% of patients achieved cure with a bedaquiline-containing regimen.ConclusionsBedaquiline-based MDR-TB treatment regimens result in better disease resolution when compared to bedaquiline-sparing MDR-TB treatment regimens under programmatic conditions in a country with a high-burden of MDR-TB.

Emergence of bedaquiline resistance in a high tuberculosis burden country

“…Based on the result of a systematic review and a meta-analysis, the World Health Organization (WHO) revised the guidelines for the management of patients with MDR-TB by prioritizing the fluoroquinolones, bedaquiline and linezolid (all classified as group A agents) in 2019 [2,4]. Especially the recently introduced novel anti-TB drug bedaquiline raised great expectations with the potential to reduce death rates [5], shorten MDR-TB treatment durations [6], decrease treatment failure rates [7][8][9][10] and thus has been administered to MDR-TB patients in more than 50 countries to date [11,12]. Another important aspect is that MTBC isolates are considered naïve to bedaquiline as it was never administered under programmatic conditions, though recently a study indicated pre-existing bedaquiline resistance predating the introduction of the drug in Southern Africa [13].…”

Safety, efficacy, and serum concentration monitoring of bedaquiline in Chinese patients with multidrug-resistant tuberculosis

“…Bedaquiline significantly improved treatment outcomes of MDR-TB. Data from a retrospective cohort study showed that bedaquiline-based MDR-TB treatment regimens resulted in better disease resolution than bedaquiline-sparing MDR-TB treatment regimens in a country with a high burden of MDR-TB (Chesov et al, 2021). A study in South African TB patients by Ndjeka et al suggested that bedaquiline was associated with a high rate of successful treatment outcomes for MDR-TB (Ndjeka et al, 2018).…”

Lactated Ringer's solution versus normal saline in pediatric living‐donor liver transplantation: A matched retrospective cohort study

“…Although an SMD value of <0.1 is usually considered to indicate a good balance between two groups for a given variable, an SMD below 0.2 is also considered to indicate a satisfactory balance. 18,19 Therefore, in the present study SMD<0.2 was utilized to assess the balance within the matched cohorts. SMDs before and after propensity score matching were determined using the package "cobalt" of the statistical software R version 3.3.3 (R Foundation).…”