Rifampicin 150mg / Isoniazid 100mg tablets

Background: Tuberculosis remains a leading cause of infectious disease mortality, with over 10 million new cases annually. The standard first-line regimen—isoniazid, rifampicin, pyrazinamide, and ethambutol—has dramatically improved survival, yet drug-induced micronutrient depletion, particularly zinc, is an underappreciated complication that may contribute to treatment-related morbidity. Ethambutol-induced optic neuropathy (EON) affects 1–5% of treated patients, and accumulating evidence implicates zinc chelation as its central mechanism. We hypothesize that anti-TB therapy creates a “multi-hit” zinc depletion state through convergent drug- and disease-mediated pathways. Methods: We conducted a systematic search of PubMed, Scopus, Web of Science, and Cochrane databases from 1944 (discovery of streptomycin) through March 2026. Search terms combined anti-TB drug names with zinc, copper, micronutrient, optic neuropathy, and visual loss. We included randomized controlled trials, cohort studies, case-control studies, case series, in vitro investigations, and animal models. PRISMA 2020 guidelines were followed. Risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies and the Cochrane RoB 2.0 tool for trials. Results: From 2,847 initial records, 186 studies met inclusion criteria. Serum zinc was significantly lower in TB patients versus controls (pooled mean difference: −12.1 μmol/L; 95% CI: −14.5 to −9.7; I² = 68%). Ethambutol directly chelates zinc and copper in retinal ganglion cells via its metabolite EDBA, causing lysosomal membrane permeabilization and mitochondrial dysfunction. Isoniazid depletes pyridoxine, impairing zinc-dependent enzymatic cascades. Rifampicin induces CYP3A4 via PXR activation, accelerating retinol catabolism and functionally coupling zinc deficiency to vitamin A insufficiency through impaired retinol-binding protein synthesis. The zinc–vitamin A axis demonstrates a strong positive correlation (r = 0.86, p < 0.01) in TB cohorts. Zinc supplementation (50 mg elemental zinc/day) improved sputum conversion rates and reduced hepatotoxicity markers in three randomized trials. Conclusions: Anti-TB drugs collectively create a “multi-hit” zinc depletion syndrome that extends beyond simple ethambutol chelation. We propose a clinical algorithm for baseline zinc assessment, risk stratification, and prophylactic supplementation during TB therapy. Persistent visual loss despite ethambutol discontinuation should prompt evaluation of concurrent zinc depletion from isoniazid, rifampicin, and the underlying TB disease itself.

Abstract licence: CC BY

BackgroundTreatment of tuberculosis infection (TBI) is a key pillar of the WHO End TB Strategy. Two short-course rifamycin-based regimens-weekly isoniazid plus rifapentine for 12 weeks (3HP) and daily rifampicin for 16 weeks (4RIF)-are widely recommended; however, they have not previously been directly compared in a randomised controlled trial. We compared treatment completion between 3HP and 4RIF among individuals with TBI.MethodsWe conducted a multicentre, open-label, parallel-group randomised controlled trial across seven tuberculosis clinics in Sydney, Australia, between July 2019 and June 2024. Participants of any age with TBI were randomised 1:1, stratified by site, to receive either weekly 3HP or daily 4RIF. All doses were self-administered. Participants in the 3HP group received weekly SMS adherence reminders; both groups received standard clinic follow-up. The primary outcome was treatment completion, defined as ingestion of ≥90% of prescribed doses. Analyses were conducted on an intention-to-treat basis.ResultsA total of 210 participants were enrolled (106 assigned to 3HP and 104 to 4RIF). Treatment completion was significantly higher in the 3HP group (84.9%) compared with the 4RIF group (65.4%; relative risk 1.30, 95% CI 1.22-1.38; pConclusionWeekly 3HP supported by SMS reminders achieved significantly higher treatment completion than daily 4RIF, with similar safety. These findings support broader implementation of 3HP to optimise adherence and outcomes in TBI programs.

Abstract licence: CC BY-NC-SA

BackgroundClose contacts of individuals with active pulmonary tuberculosis (TB) face an elevated risk of TB acquisition, necessitating systematic screening for latent TB infection and subsequent TB preventive treatment (TPT). Major TPT regimens require ≥3 months of drug exposure and demonstrate suboptimal safety profiles, significantly compromising treatment completion rates. Therefore, the development of shorter, safer chemoprophylaxis strategies represents a critical need in global TB control. Among close contacts, school-aged children and adolescents constitute the most vulnerable demographic subgroup, warranting prioritized intervention efforts.ObjectiveThe primary objective of this study is to demonstrate noninferiority of an ultrashort, 1-month TPT regimen of isoniazid plus rifapentine, administered 3 times a week (1H3P3) compared with the standard 3-month daily isoniazid plus rifampicin (3HR) regimen in preventing active TB, as measured by the 24-month cumulative incidence of active TB following randomization.MethodsAn investigator-initiated, prospective, multicenter, open-label, noninferiority, cluster-randomized controlled clinical trial is being implemented under the auspices of the national TB control program in China. Close contacts of school pulmonary TB index cases, regardless of diagnostic type, are actively screened for symptoms using interferon-gamma release assays, chest imaging, and sputum molecular diagnostic testing to detect TB infection and exclude active TB. Eligible latent TB infection cases will be randomized in a 1:1 cluster ratio to receive either the standard 3HR regimen or the novel ultrashort 1H3P3 regimen for TPT, with subsequent follow-up for up to 2 years to assess disease progression. The primary composite end point includes microbiologically confirmed TB (sputum culture or molecular diagnostic testing) or clinically diagnosed TB. With 80% power to detect noninferiority (20% margin), the study requires 1760 participants per arm, accounting for cluster design effects.ResultsRecruitment started in September 2023. By the end of December 2025, a total of 2478 participants, comprising 627 index cases, had been enrolled, and recruitment is estimated to continue until September 2026. Data analysis will commence after the 2-year follow-up period, and the results are expected to be published by March 2029.ConclusionsThis cluster randomized controlled trial aims to establish the noninferiority of a novel, ultrashort 1H3P3 regimen compared to the standard 3-month 3HR regimen for preventing active TB in infected school contacts. If successful, this well-tolerated 1-month regimen could significantly improve treatment completion and optimize preventive therapy delivery in high-transmission congregate settings, thereby contributing substantively to global TB control efforts.

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BackgroundCurrent combination antibiotic treatment for drug-susceptible tuberculosis (DS-TB) usually takes 6 months to complete. This long duration can compromise clinical outcomes. Although a 4-month regimen including an optimized dose of rifapentine plus moxifloxacin is non-inferior to standard therapy, rifapentine is hard to source globally and adoption of this regimen has been slow. This trial investigates the efficacy and safety of a 4-month DS-TB treatment including the more readily available rifamycin, rifampicin 35 mg/kg, with or without moxifloxacin 400 mg.MethodsThis multi-centre phase III randomized open-label clinical trial will be conducted across four African countries (Gabon, Malawi, Mozambique and Tanzania). A total of 414 newly diagnosed consenting adult participants will be block randomized, after stratification by chest radiograph cavitation, to two experimental and one control arm at a ratio of 1:1:1. The first experimental group will receive optimized dose rifampicin (35 mg/kg) with routine weight-banded doses of isoniazid, pyrazinamide, and ethambutol once daily for 4 months. The second experimental group will receive optimized dose rifampicin (35 mg/kg) and moxifloxacin 400 mg once daily alongside routine doses of isoniazid and pyrazinamide. The control group will receive 6-month standard of care therapy: rifampicin (10 mg/kg) plus weight-banded dose of isoniazid, pyrazinamide, and ethambutol for 2 months, followed by the same doses of rifampicin and isoniazid for 4 months. Participants will be followed until the allocation of efficacy (TB-free survival) and safety (proportion of severe adverse events) outcomes. Secondary outcomes will also include the evaluation of the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) for microbiological treatment monitoring.DiscussionThis study will evaluate whether 4-month duration multi-drug treatment including an optimized dose of rifampicin with or without moxifloxacin has non-inferior efficacy and safety outcomes compared to standard of care DS-TB therapy in Africa.Trial registrationClinicalTrials.gov NCT05575518. Registered on 10th October 2022.

Abstract licence: CC BY-NC-ND