Delamanid 50mg tablets

Tuberculosis (TB) remains the deadliest Infectious disease worldwide, partially due to the increasing dissemination of multidrug and extensively drug-resistant (MDR/XDR) strains. Drug regimens containing the new anti-TB drugs bedaquiline (BDQ) and delamanid (DLM) appear as a last resort for the treatment of MDR or XDR-TB. Unfortunately, resistant cases to these drugs emerged just one year after their introduction in clinical practice. Early detection of resistant strains to BDQ and DLM is crucial to preserving the effectiveness of these drugs. Here, we present a systematic review aiming to define all available genotypic variants linked to different levels of resistance to BDQ and DLM that have been described through whole genomic sequencing (WGS) and the available drug susceptibility testing methods. During the review, we performed a thorough analysis of 18 articles. BDQ resistance was associated with genetic variants in Rv0678 and atpE, while mutations in pepQ were linked to a low-level of resistance for BDQ. For DLM, mutations in the genes ddn, fgd1, fbiA, and fbiC were found in phenotypically resistant cases, while all the mutations in fbiB were reported only in DLM-susceptible strains. Additionally, WGS analysis allowed the detection of heteroresistance to both drugs. In conclusion, we present a comprehensive panel of gene mutations linked to different levels of drug resistance to BDQ and DLM.

Abstract licence: CC BY 4.0

ObjectiveThis scoping review aims to identify and map the available evidence on interventions for the prevention and treatment of childhood TB, confirm current practice, explore variation, and identify emerging approaches.Study designScoping review.MethodThis scoping review was conducted using established methods and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The protocol was registered with the Open Science Framework. Selection criteria were defined using the PCC framework, including population (children aged 0-18 years), concept (prevention and treatment of tuberculosis), and context (global settings). Studies with control groups were included, such as randomised controlled trials (RCTs), quasi-experimental studies, cohort studies, case-control studies, and cross-sectional studies. Electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, and EMBASE) and websites of global health agencies (e.g., USAID, UNICEF, WHO, and CDC) were searched.ResultsFollowing a comprehensive search and screening process, 41 studies were included. Of these, 15 were conducted in the African region (with South Africa contributing the most, n = 7), followed by Southeast Asia (n = 12), Europe (n = 6), the Western Pacific (n = 4), the Eastern Mediterranean (Pakistan, n = 2), the Americas (USA, n = 1), and one multi-country study. Eighteen studies focused on TB prevention, 22 on treatment, and one on both. The review found that combining pharmaceutical and non-pharmaceutical interventions improved prevention outcomes, with treatment completion rates reaching up to 99% and reductions in mortality. The BCG vaccine showed variable efficacy (22-92%), with over 70% protection against TB meningitis reported in several regions. Treatment success rates for drug-sensitive TB reached up to 97%. New regimens incorporating bedaquiline and delamanid for multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) showed cure rates as high as 94.6%.ConclusionOverall, shorter treatment regimens were associated with higher completion rates, although evidence on long-term cure remains limited.

Abstract licence: CC BY-NC-ND

BackgroundChildren and adolescents with multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (TB) face major treatment challenges. Although newer all-oral regimens have transformed adult TB care, their use in younger populations has largely been extrapolated from adult studies, despite important biologic and clinical differences. Systematic and up-to-date evidence on the effectiveness and safety of contemporary regimens in children and adolescents is lacking. We conducted a global systematic review and meta-analysis to address this gap.MethodsWe systematically searched PubMed, EMBASE, Web of Science, Cochrane Library and Google Scholar for studies published between January 1, 2015, and September 1, 2025. Eligible studies included children 0-19 years old with confirmed or presumed MDR/XDR-TB or rifampicin-TB receiving pharmacologic treatment. Outcomes were pooled using a random-effects meta-analysis. The primary outcome was treatment success (cure or completion); severe (grade 3/4) adverse events were assessed as secondary outcomes.ResultsWe included 14 studies comprising 490 children across 13 countries. Overall pooled treatment success was 89% (95% confidence interval: 84%-93%; I2 = 51.9%). Newer all-oral regimens achieved slightly higher success (91%) than injectable-containing regimens (83%). Severe grade 3/4 adverse event were sparse (7 of 14 studies); events occurred in 21% (95% confidence interval: 13%-33%), most commonly QT prolongation and anemia, with limited specific drug attribution.ConclusionsNewer, all-oral bedaquiline- and delamanid-based regimens for pediatric MDR/XDR-TB are effective and generally well tolerated, though the full safety profile remains incompletely characterized. In pediatric MDR/XDR-TB, where studies are rare, our findings provide the best available evidence and a foundation for improved treatment guidelines and future research.

Abstract licence: CC BY-NC-ND

BackgroundDrug-resistant tuberculosis remains a major public health challenge with substantial associated morbidity and mortality. Management requires complex, individualized treatment regimens. Emerging evidence suggests that contemporary antituberculosis agents for drug-resistant disease carry significant cardiotoxicity risk. This study aims to evaluate the cardiovascular toxicity of current therapeutic regimens in patients with multidrug-resistant, pre-extensively drug-resistant, and extensively drug-resistant tuberculosis.MethodsThis systematic review and meta-analysis was conducted following the PRISMA guidelines. A comprehensive literature search was performed across five databases (PubMed, Cochrane Library, Scopus, ProQuest, and Springer) through May 5, 2024. Methodological quality was assessed using NHLBU study quality assessment tools for controlled intervention studies. Statistical analyses were conducted using a random-effects model with the DerSimonian-Laird method, with results reported as pooled estimates with 95% confidence intervals.ResultsEight studies comprising 9,506 patients with multidrug-resistant, pre-extensively drug-resistant, and extensively drug-resistant tuberculosis were included. Bedaquiline without delamanid was associated with the greatest QTc prolongation [pooled mean difference: 21.9 ms (95% CI [10.24-33.62])] and highest prevalence of clinically significant QTc prolongation [21.2% (95% CI [8.6-22.8]%)]. Treatment discontinuation rates were similar for bedaquiline monotherapy and bedaquiline-delamanid combination therapy [8% (95% CI [2-18]%) vs. 8% (95% CI [0-21]%)].ConclusionDrug resistant tuberculosis treatments were associated with cardiotoxicity concerns, evidenced by its QT prolongation, clinically significant arrhythmia, and treatment discontinuation.

Abstract licence: CC BY