Detection of a historic reservoir of bedaquiline/clofazimine resistance-associated variants in Mycobacterium tuberculosis.

Background: Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug.

Differentiated service delivery framework for people with multidrug-resistant tuberculosis and HIV co-infection.

Introduction: For people living with HIV/AIDS, care is commonly delivered through Differentiated Service Delivery (DSD). Although people with multidrug-resistant tuberculosis (MDR-TB) and HIV/AIDS experience severe treatment associated challenges, there is no DSD model to support their treatment. In this study, we defined patterns of medication adherence and characterized longitudinal barriers to inform development of an MDR-TB/HIV DSD framework.

Baseline and treatment-emergent bedaquiline resistance in drug-resistant tuberculosis: a systematic review and meta-analysis.

Bedaquiline resistance is a major threat to drug-resistant tuberculosis control strategies. This analysis found a pooled prevalence of baseline bedaquiline resistance of 2.4% and a pooled prevalence of treatment-emergent bedaquiline resistance of 2.

Higher plasma interleukin - 6 levels are associated with lung cavitation in drug-resistant tuberculosis.

Background: Lung cavitation is associated with heightened TB transmission and poor treatment outcomes. This study aimed to determine the relationship between systemic inflammation and lung cavitation in drug-resistant TB patients with and without HIV co-infection.

Methods: Plasma samples were obtained from 128 participants from the CAPRISA 020 Individualized M(X)drug-resistant TB Treatment Strategy Study (InDEX) prior to treatment initiation.

Isoniazid resistance-conferring mutations are associated with highly variable phenotypic resistance.

Background: High-dose isoniazid is recommended in the 9-12 months short-course regimen for multidrug-resistant tuberculosis with mutation. However, there is insufficient evidence to support the assumption of genotypic-phenotypic concordance. This study aimed to identify the genetic mutations associated with high-level phenotypic isoniazid resistance.