Ethambutol 200mg/5ml oral solution

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.

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Background: The retinal changes caused by ethambutol are not clear in patients with the administration of ethambutol and without ethambutol-induced optic neuropathy (EON). The aim of this systematic review is to estimate the changes in retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer (GCIPL) thicknesses measured by optical coherence tomography (OCT) in patients with mycobacterial infection treated with ethambutol and not suffering from EON. Methods: A systematic review of articles was conducted by searching PubMed, Embase, and Web of Science until November 2025. Additional studies were identified by the review of references. Search terms included OCT and ethambutol. Longitudinal observational studies using an OCT device to measure RNFL and GCIPL thicknesses before and after the administration of ethambutol in patients with mycobacterial infection without ocular diseases were included. The extraction of data in studies was performed by two researchers using data extraction sheets. The meta-analysis was conducted using the random-effect model. Results: In total, 14 studies (n = 1138) were eligible for the systematic review. Meta-analysis combining RNFL measured after the longest duration of ethambutol administration showed no significant decrease compared to RNFL before treatment. However, there were significant decreases in RNFL thickness in male-dominant studies, studies conducted in Turkey and India, and studies conducted by the Cirrus OCT device. In addition, the decreases in RNFL thickness were correlated with the duration of ethambutol administration in male-dominant studies. Only two studies reported the thickness changes in GCIPL, and the study with a higher male proportion showed significant decreases in GCIPL thickness. Conclusions: Ethambutol does not cause a significant RNFL decrease generally in mycobacterial infection patients; however, it may lead to decreased RNFL thickness in male patients and patients in some regions, even though they do not suffer from EON.

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BackgroundMycobacterium riyadhense is an emerging nontuberculous mycobacterium associated with infections in immunocompetent and immunocompromised patients.MethodsTo identify the epidemiology, risk factors, presentations, and antimicrobial susceptibility of M. riyadhense, we conducted a systematic review on PubMed, Web of Science, and Google Scholar adhering to PRISMA guidelines. We included publications during 2009-2025, with no limitation on language or study design. Cases of uncertain infection or identification were excluded. Review protocol was pre-registere in PROSPERO with protocol number; CRD420250653025.ResultsWe identified 22 studies reporting on 69 cases of M. riyadhense. Patient median age was 35.5 and 80% were male. Common presentations included pneumonia (n=52), lymphadenitis (n=13), osteomyelitis (n=8), or disseminated infection (n=8). Susceptibility to Rifampin and Ethambutol was observed in all tested isolates. Resistance to Isoniazid was detected in 5/8 isolates.ConclusionThis review identified a significant variability in the diagnosis and treatment of M. riyadhense. This underscores the urgent need for standardized diagnostic protocols and targeted treatment strategies to effectively manage infections.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420250653025.

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BackgroundTuberculosis affects over a million children annually. Ethambutol (EMB) is a key component of the standard four-drug therapy for drug-susceptible tuberculosis in children, yet comprehensive pharmacokinetic studies have been lacking. We characterized the population pharmacokinetics of EMB through an individual patient data meta-analysis to determine optimal dosing strategies.MethodsEMB concentrations and individual-level patient data from three studies were analyzed using nonlinear mixed effects modeling. Simulations compared current World Health Organization (WHO)-recommended doses and model-informed optimized doses. Target exposure distribution (AUC 13.8-17.7 mg·h/L), which had been previously established in adult clinical trials, guided dose optimization.ResultsA total of 220 participants, aged from 0.2 to 15 years and weighing between 3.6 and 43.0 kg, contributed 1,085 plasma concentrations of EMB for model development. The effect of weight was incorporated on clearance, intercompartmental clearance, and volume of distribution in both the central and peripheral compartments. Age affected clearance through a maturation function. Simulations indicated children weighing less than 25 kg had median exposures below the target exposure distribution at current WHO-recommended doses. Under the optimized weight band dosing, approximately 40.5% of the patients would receive a higher dose, and an additional 5% points of patients may benefit from this adjustment.ConclusionOur IPDMA supports the revision of current pediatric EMB dosing guidelines for the treatment of tuberculosis. Our findings aim to ensure adequate drug exposure across all pediatric weight bands, while also accounting for toxicity and challenges related to formulation implementation and adherence.

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