All-oral longer regimens are effective for the management of multidrug-resistant tuberculosis in high-burden settings

Abstract

BackgroundRecent World Health Organisation guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline- and/or delamanid as part of their multidrug regimen.MethodsPatients with a positive baseline culture were included. Six-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods.ResultsCulture conversion was observed in 83.8% (526/628) of patients receiving an all-oral regimen and 85.5% (425/497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95%CI: 0.88–1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients.ConclusionsAmong individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study.

Effectiveness of a bedaquiline, linezolid, clofazimine “core” for multidrug-resistant tuberculosis

“…These modest increases in effectiveness may be due to true differences, chance, or residual confounding. 24 The relatively small sample size for this analysis forced us to balance confounder adjustment and model stability, and therefore we focused on the strongest and most likely confounders. Therefore, residual confounding is a possibility.…”

Surveillance of multidrug-resistant tuberculosis in sub-Saharan Africa through wastewater-based epidemiology

“…The results obtained in this study, which is the detection of ARGs associated with TB treatment in varying concentrations, give a snapshot of the profile of TB resistance within the communities of the selected African countries. The highest concentrations of genes conferring resistance to first-line TB drugs in South Africa, in both untreated and treated wastewater, could be due to the high incidence of TB in the country [ 5 , 23 ]. South Africa has been reported as one of 30 high TB/HIV burden countries [ [24] , [25] ].…”

Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China

“…Prior to August 2018, RR/MDR-TB treatment guidelines recommended parenteral administration of capreomycin or aminoglycoside (kanamycin or amikacin) as part of the treatment [30]. However, due to the significant toxicity and patient intolerance that led to treatment interruption [31], the WHO deprioritized the injectable-containing regimens in 2019 and recommended the use of all-oral regimens [30]. Therefore, although the treatment success rate and culture conversion rate in the present study were slightly higher in patients treated with BDQ and injectable agents than in those who did not receive injectable agents, an all-oral BDQ-based regimen was recommended for the treatment of patients with refractory RR/MDR/XDR-TB.…”