Ethambutol 700mg/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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IntroductionTuberculosis (TB) and its treatment have been associated with significant neuro-ophthalmic morbidity; however, the magnitude and determinants of these complications remain incompletely characterized. This systematic review and meta-analysis aimed to evaluate the incidence and risk factors of ethambutol optic neuropathy (EON), neuro-ophthalmic manifestations of tuberculous meningitis (TBM), and prognostic biomarkers for visual outcomes.MethodsFollowing PRISMA 2020 guidelines, we searched PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Google Scholar up to the 30th of September 2025. Studies reporting EON incidence, TBM neuro-ophthalmic complications, or subclinical neurotoxicity biomarkers were included. Random-effects meta-analysis with generalized linear mixed models was performed.ResultsTwenty-two studies (N = 260,430) were included. Pooled EON incidence was 1.54% (95% CI: 0.81-2.49%, I²=98.2%). Renal impairment (OR 3.73, 95% CI: 1.78-7.83) and hypertension (OR 2.37, 95% CI: 1.46-3.84) were significant risk factors. TBM neuro-ophthalmic manifestations included cranial nerve III palsy (17.4%), papilledema (12.5%), and optic atrophy (16.7%), with pediatric patients demonstrated significantly higher hydrocephalus rates (72.5% vs 13.0%, RR 5.56). Visual evoked potential (VEP) demonstrated better detection of subclinical changes over optical coherence tomography (OCT) (Hedges' g difference: 0.686, P-value = 0.001). Visual recovery occurred in 52.4% of clinical EON cases. Factors associated with improved recovery included younger age (MD= -3.8 years, P-value= 0.095) and earlier ethambutol discontinuation.ConclusionsTB-related neuro-ophthalmic complications represent significant morbidity with identifiable risk factors. Visual evoked potentials offer superior subclinical detection and early intervention improves visual outcomes. Screening protocols targeting high-risk populations are recommended.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251141453.

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Whole-genome sequencing (WGS) accelerates drug-susceptibility testing (DST) in Mycobacterium tuberculosis (Mtb). Open-access software tools have become widely available, but the sources of real-world performance variability remain uncharacterized. We performed a systematic review and meta-analysis of the performance of open-access, independently validated WGS-based DST prediction tools. Bivariate random-effects meta-analysis was performed for six maintained tools (TBProfiler, Mykrobe, PhyResSE, MTBseq, GenTB, and SAM-TB). Bivariate meta-regression identified covariates associated with performance variation. Thirty-nine studies comprising 144,623 genomes were included. For the two most extensively validated tools, TBProfiler and Mykrobe, pooled rifampicin sensitivity was 95.4% (95% CI: 93.5-96.7) and 93.7% (92.0-95.1), with a specificity of 97.3% (95.7-98.3) and 97.0% (94.8-98.3), respectively. For isoniazid, the sensitivity was 92.0% (90.4-93.3) and 88.2% (85.5-90.4) and specificity 97.3% (96.0-98.2) and 97.5% (95.8-98.5). For ethambutol, the specificity was heterogeneous across tools (86.5%-95.4%); for pyrazinamide, the sensitivity varied widely (49.9%-80.6%). For fluoroquinolones, both sensitivity and specificity approached 90%, with heterogeneity. For newer agents, data scarcity precluded meaningful assessment. Meta-regression identified rifampicin resistance prevalence as the dominant predictor of decreased specificity across first-line drugs (β -1.5 to -3.6 on logit scale, false discovery rate [FDR] q Mycobacterium tuberculosis offers the potential to rapidly predict drug resistance as a one-stop test, but the accuracy of the software tools used to interpret sequencing results has been inconsistently reported. This meta-analysis leverages the heterogeneity across 39 studies and 144,623 genomes to identify factors that drive inconsistencies in reported performance, providing context-specific guidance for clinical adoption. We show that most tools perform adequately as rule-out tests for resistance to the most important first- and second-line drugs but fall short of specificity targets. Importantly, we identify that the local burden of drug resistance in a study population is the dominant factor driving inconsistencies between reported performance estimates. These findings provide guidance for laboratories considering adopting sequencing-based resistance testing and specify priorities for future tool development and validation.

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Whole-genome sequencing (WGS) is an increasingly adopted platform for predicting drug resistance in Mycobacterium tuberculosis; however, diagnostic accuracy varies substantially across bioinformatic tools and analytical frameworks, generating considerable uncertainty for clinical laboratory implementation. We conducted a prospectively registered (PROSPERO: CRD420261342739), PRISMA-DTA-compliant systematic review and meta-analysis of diagnostic accuracy studies. PubMed (MEDLINE), Embase, Web of Science, and Cochrane CENTRAL were searched from 1 January 2000 through 28 January 2026. Primary overall sensitivity and specificity were estimated using a tool-level bivariate random-effects model. Exploratory subgroup analyses and meta-regression examined the association between algorithm category and diagnostic-performance heterogeneity. Twenty-eight drug-level evaluations from seven tools (rifampicin, isoniazid, ethambutol, and pyrazinamide for each tool) were compiled from the extracted 2 × 2 data. For the primary tool-level composite analysis, pooled sensitivity was 0.930 (95% CI: 0.907-0.948) and pooled specificity was 0.962 (95% CI: 0.929-0.981). In secondary drug-specific analyses, sensitivity was highest for rifampicin (0.960, 95% CI: 0.934-0.976) and isoniazid (0.933, 95% CI: 0.906-0.953), and lowest for pyrazinamide (0.860, 95% CI: 0.800-0.904). Exploratory tool-level comparisons produced pooled sensitivity estimates of 0.920 for rule-based tools, 0.899 for machine learning tools, and 0.951 for hybrid tools. These comparisons involved only seven tool-level analytic units and cannot disentangle algorithm type from individual tool identity, training data, mutation catalogue version, or validation population. WGS-based bioinformatic tools provide highly specific and generally sensitive predictions of Mycobacterium tuberculosis resistance for first-line drugs across diverse clinical settings. Exploratory differences between tool categories should not be interpreted as causal effects of algorithmic architecture. Future studies should use prospective head-to-head evaluations on shared, geographically diverse isolate collections, alongside continued improvement of resistance catalogues and external validation.

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Accurate drug susceptibility testing (DST) is crucial for designing effective regimens for multidrug-resistant (MDR) and pre-extensively drug-resistant tuberculosis (pre-XDR TB). Sensititre MYCOTB enables simultaneous determination of minimum inhibitory concentrations (MICs) for multiple drugs, but its diagnostic performance varies across studies. This meta-analysis evaluated the diagnostic performance of Sensititre MYCOTB for key MDR and pre-XDR TB drugs. The protocol was registered in PROSPERO (CRD420251230599). PubMed, Cochrane, Google Scholar, Scopus, ONOS, Web of Science, ScienceDirect, and registries were systematically searched for studies published between 2010 and 2025. Studies comparing the Sensititre MYCOTB with reference DST for Mycobacterium tuberculosis complex (MTBC) were included. Bias assessment and pooled diagnostic accuracy estimates were generated. Fourteen studies, including 1,728 isolates, were analyzed. Rifampicin and isoniazid demonstrated high sensitivity (0.976 [95% CI: 0.94-0.99] and 0.977 [95% CI: 0.95-0.99]) and specificity (0.958 [95% CI: 0.84-0.98] and 0.957 [95% CI: 0.83-0.99], respectively) with low heterogeneity. Amikacin, kanamycin, and ofloxacin demonstrate good diagnostic accuracy, with high specificity (>0.98 [95% CI]). Moderate diagnostic accuracy was observed for ethambutol, streptomycin, ethionamide, and rifabutin. Cycloserine, moxifloxacin, and para-aminosalicylic acid showed inconsistent performance despite excellent specificity (>0.97 [95% CI]). Sensitivity analysis partially improved pooled sensitivity for moxifloxacin 0.801 (95% CI: 0.585-0.924) and para-aminosalicylic acid 0.76 (95% CI: 0.518-0.894), whereas cycloserine remained at 0.436 (95% CI: 0.190-0.725), although heterogeneity persisted. Sensititre MYCOTB DST demonstrates high diagnostic accuracy for MDR-TB and pre-XDR-TB drugs, while caution is required with cycloserine, moxifloxacin, and para-aminosalicylic acid. These findings support the integration of MIC-based testing into clinical decision-making.

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