Generic Rifater tablets

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.

Abstract licence: CC BY

Study DesignSystematic review and meta-analysis.ObjectiveTo evaluate the prevalence, patterns, diagnosis, and management of drug-resistant spinal tuberculosis (TB).MethodsWe systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane database from database inception to 14 February 2026, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Observational and experimental studies reporting drug resistance among patients with spinal TB were included. A random-effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals (CI). Risk of bias was assessed using the Joanna Briggs Institute checklist.ResultsNineteen studies involving 5,475 patients with spinal TB were included. The pooled prevalence of multidrug-resistant (MDR)-TB among spinal TB was 4.69% (95% CI: 3.03-7.20%; 16 studies). Rifampicin resistance was noted in 13.84% (95% CI: 3.07-44.90%; 6 studies). Drug susceptibility testing was most commonly performed after clinical or radiological non-response rather than as routine practice. Treatment approaches were heterogeneous, with MDR spinal TB typically managed using individualized second-line anti-TB regimens, frequently combined with surgical intervention. Low risk of bias was documented in 47.4% of studies.ConclusionsThe prevalence of MDR-TB among spinal tuberculosis was 4.69%. Considerable heterogeneity exists in drug susceptibility testing, diagnosis, medical treatment, and surgical management. The available evidence remains limited, underscoring the need for prospective studies evaluating the effectiveness of anti-TB regimens in MDR spinal tuberculosis.

Abstract licence: CC BY-NC-ND

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.

Abstract licence: CC BY

BackgroundAlthough children are at a higher risk of progressing to tuberculosis (TB) disease compared with adults, research and publications addressing TB management have mostly emphasised adult disease.MethodsMEDLINE, Embase, CENTRAL and grey literature were searched from inception to 3 May 2021, and updated on 12 December 2024 for the systematic review and network meta-analysis (NMA). Randomised controlled trials of children and/or adolescents under 18 years with TB infection, contacts of drug-susceptible TB, without HIV, evaluating the effectiveness and safety of available regimens for the treatment of TB were included. Meta-analysis was conducted using a random effects model. Risk of bias was assessed using the Cochrane RoB tool 2. Effect estimates (RR and OR) are presented with 95% CIs. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.ResultsEleven studies were obtained. All network geometries had open and disconnected loops, except adverse reactions for which we conducted a full NMA. We found that 4 months of isoniazid and rifampicin (4HR) reduces the number of active TB cases at 1 year, 2 years and 5 years of follow-up (RR 0.49 (95% CI 0.32 to 0.76)) compared with isoniazid for 9 months (9H). The isoniazid + rifapentine for 3 months (3HP) regimen (RR 1.09 (95% CI 1.03 to 1.15)), 4HR (RR 1.07 (95% CI 1.01 to 1.14)) and rifampicin for 4 months (4R) (RR 1.12 (95% CI 1.05 to 1.20)) regimens have higher treatment adherence compared with 9H. High variability was found in the reporting of adverse reactions, which were more likely to occur with 3HP compared with 4HR (OR 4.56 (95% CI 1.22 to 16.96)) and 4R (OR 6.37 (95% CI 2.11 to 19.19)). Adverse reactions occur less frequently with 4R (OR 0.34 (95% CI 0.20 to 0.58)) compared with 9H.ConclusionsThis study synthesised available data on paediatric short and long-course regimens. Short course regimens may have higher adherence (3HP, 4HR, 4R) and may reduce active TB incidence (isoniazid + rifampicin for 3 months (3HR) and 4HR) compared with 9H.Prospero registration numberCRD42021271512.

Abstract licence: CC BY-NC