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The Lancet. Microbe Feb 2024Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
METHODS
We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
FINDINGS
18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
INTERPRETATION
Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
FUNDING
Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Topics: United States; Humans; Antitubercular Agents; Diarylquinolines; Tuberculosis; Mycobacterium tuberculosis; Genomics
PubMed: 38215766
DOI: 10.1016/S2666-5247(23)00317-8 -
The Medical Journal of Malaysia Mar 2024Inappropriate treatment and non-adherence use of anti-tuberculosis (TB) drugs trigger the spread of multidrug-resistant tuberculosis (MDR-TB) strains and causes an... (Review)
Review
INTRODUCTION
Inappropriate treatment and non-adherence use of anti-tuberculosis (TB) drugs trigger the spread of multidrug-resistant tuberculosis (MDR-TB) strains and causes an emerging public health threat worldwide. Therefore, non-adherence to MDR-TB treatment leading to prolonged medication period, increase incidence of adverse event and financial burden, thus it requires interventions to achieve a therapeutic outcome.
OBJECTIVE
This scoping review aims to provide an overview of interventions to improve the adherence level to medication of MDR-TB patients.
MATERIALS AND METHODS
A review of observational studies was conducted to discuss the accuracy, tolerability and ease of use of tonometers in measuring IOP in children with glaucoma. Three databases (PubMed, Web of Science, Scopus) were used in a scoping review. The data were synthesised using Rayyan AI. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to guide this review.
RESULTS
A total of 11 articles were included in this review to describe the various interventions in MDR-TB treatment adherence. Psychological counselling or education intervention was the most popular intervention, and it significantly increased adherence levels among MDR-TB patients. Increased adherence level patients also reported by interventions with Medication Event Reminder Monitor (MERM), Video Directly Observed Therapy (VDOT), 30-day recall and Visual Analogue Scale (VAS), Financial Support, mHealth Application and directly observed therapy, short course (DOTS) and DOTS-Plus programs. However, we found that Electronic Dose Monitoring (EDM) device intervention has less effect on MDR-TB patients' adherence.
CONCLUSION
The recovery of patients can be facilitated through MDR-TB treatment adherence interventions. It is acknowledged that the studies included in this review exhibit heterogeneity, with a majority showing significant improvement. Therefore, further study was required to investigate the specific on developing highly personalised interventions tailored to specific population or context, as well as to assess the cost-effectiveness of such interventions.
Topics: Child; Humans; Tuberculosis, Multidrug-Resistant; Antitubercular Agents; Medication Adherence
PubMed: 38553929
DOI: No ID Found -
Journal of Global Antimicrobial... Sep 2023The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline... (Meta-Analysis)
Meta-Analysis Review
Evaluation of genetic mutations associated with phenotypic resistance to fluoroquinolones, bedaquiline, and linezolid in clinical Mycobacterium tuberculosis: A systematic review and meta-analysis.
OBJECTIVES
The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline (BDQ), and linezolid (LZD)) are crucial drugs for the control of MDR-TB. Molecular drug resistance assays could facilitate the effective use of Group A drugs.
METHODS
We summarised the evidence implicating specific genetic mutations in resistance to Group A drugs. We searched PubMed, Embase, MEDLINE, and the Cochrane Library for studies published from the inception of each database until July 1, 2022. Using a random-effects model, we calculated the odds ratios and 95% confidence intervals as our measures of association.
RESULTS
A total of 5001 clinical isolates were included in 47 studies. Mutations in gyrA A90V, D94G, D94N, and D94Y were significantly associated with an increased risk of a levofloxacin (LFX)-resistant phenotype. In addition, mutations in gyrA G88C, A90V, D94G, D94H, D94N, and D94Y were significantly associated with an increased risk of a moxifloxacin (MFX)-resistant phenotype. In only one study, the majority of gene loci (n = 126, 90.65%) in BDQ-resistant isolates were observed to have unique mutations in atpE, Rv0678, mmpL5, pepQ, and Rv1979c. The most common mutations occurred at four sites in the rrl gene (g2061t, g2270c, g2270t, and g2814t) and at one site in rplC (C154R) in LZD-resistant isolates. Our meta-analysis demonstrated that there were no mutations associated with BDQ- or LZD-resistant phenotypes.
CONCLUSION
The mutations detected by rapid molecular assay were correlated with phenotypic resistance to LFX and MFX. The absence of mutation-phenotype associations for BDQ and LZD hindered the development of a rapid molecular assay.
Topics: Humans; Mycobacterium tuberculosis; Linezolid; Fluoroquinolones; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Levofloxacin; Phenotype
PubMed: 37172764
DOI: 10.1016/j.jgar.2023.05.001 -
The Cochrane Database of Systematic... Sep 2017Tuberculous pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculous pericarditis can impair the heart's function and cause death; long term, it can cause the membrane to fibrose and constrict causing heart failure. In addition to antituberculous chemotherapy, treatments include corticosteroids, drainage, and surgery.
OBJECTIVES
To assess the effects of treatments for tuberculous pericarditis.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register (27 March 2017); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2017, Issue 2); MEDLINE (1966 to 27 March 2017); Embase (1974 to 27 March 2017); and LILACS (1982 to 27 March 2017). In addition we searched the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal using 'tuberculosis' and 'pericard*' as search terms on 27 March 2017. We searched ClinicalTrials.gov and contacted researchers in the field of tuberculous pericarditis. This is a new version of the original 2002 review.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search outputs, evaluated study eligibility, assessed risk of bias, and extracted data; and we resolved any discrepancies by discussion and consensus. One trial assessed the effects of both corticosteroid and Mycobacterium indicus pranii treatment in a two-by-two factorial design; we excluded data from the group that received both interventions. We conducted fixed-effect meta-analysis and assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
Seven trials met the inclusion criteria; all were from sub-Saharan Africa and included 1959 participants, with 1051/1959 (54%) HIV-positive. All trials evaluated corticosteroids and one each evaluated colchicine, M. indicus pranii immunotherapy, and open surgical drainage. Four trials (1841 participants) were at low risk of bias, and three trials (118 participants) were at high risk of bias.In people who are not infected with HIV, corticosteroids may reduce deaths from all causes (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.09; 660 participants, 4 trials, low certainty evidence) and the need for repeat pericardiocentesis (RR 0.85, 95% CI 0.70 to 1.04; 492 participants, 2 trials, low certainty evidence). Corticosteroids probably reduce deaths from pericarditis (RR 0.39, 95% CI 0.19 to 0.80; 660 participants, 4 trials, moderate certainty evidence). However, we do not know whether or not corticosteroids have an effect on constriction or cancer among HIV-negative people (very low certainty evidence).In people living with HIV, only 19.9% (203/1959) were on antiretroviral drugs. Corticosteroids may reduce constriction (RR 0.55, 0.26 to 1.16; 575 participants, 3 trials, low certainty evidence). It is uncertain whether corticosteroids have an effect on all-cause death or cancer (very low certainty evidence); and may have little or no effect on repeat pericardiocentesis (RR 1.02, 0.89 to 1.18; 517 participants, 2 trials, low certainty evidence).For colchicine among people living with HIV, we found one small trial (33 participants) which had insufficient data to make any conclusions about any effects on death or constrictive pericarditis.Irrespective of HIV status, due to very low certainty evidence from one trial, it is uncertain whether adding M. indicus pranii immunotherapy to antituberculous drugs has an effect on any outcome.Open surgical drainage for effusion may reduce repeat pericardiocentesis In HIV-negative people (RR 0.23, 95% CI 0.07 to 0.76; 122 participants, 1 trial, low certainty evidence) but may make little or no difference to other outcomes. We did not find an eligible trial that assessed the effects of open surgical drainage in people living with HIV.The review authors found no eligible trials that examined the length of antituberculous treatment needed nor the effects of other adjunctive treatments for tuberculous pericarditis.
AUTHORS' CONCLUSIONS
For HIV-negative patients, corticosteroids may reduce death. For HIV-positive patients not on antiretroviral drugs, corticosteroids may reduce constriction. For HIV-positive patients with good antiretroviral drug viral suppression, clinicians may consider the results from HIV-negative patients more relevant.Further research may help evaluate percutaneous drainage of the pericardium under local anaesthesia, the timing of pericardiectomy in tuberculous constrictive pericarditis, and new antibiotic regimens.
Topics: Adrenal Cortex Hormones; Antitubercular Agents; Cause of Death; Colchicine; Drainage; HIV Seronegativity; HIV Seropositivity; Humans; Immunotherapy; Pericardiectomy; Pericarditis, Tuberculous; Pericardium; Randomized Controlled Trials as Topic
PubMed: 28902412
DOI: 10.1002/14651858.CD000526.pub2 -
JAMA May 2023Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality.
OBJECTIVE
To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF).
DATA SOURCES
PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023.
STUDY SELECTION
English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded.
DATA EXTRACTION AND SYNTHESIS
Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available.
MAIN OUTCOMES AND MEASURES
Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms.
RESULTS
A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339).
CONCLUSIONS AND RELEVANCE
No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.
Topics: Adult; Humans; Chemical and Drug Induced Liver Injury; Isoniazid; Latent Tuberculosis; Mass Screening; Quality of Life; Randomized Controlled Trials as Topic; Rifampin; United States; Antitubercular Agents; Practice Guidelines as Topic
PubMed: 37129650
DOI: 10.1001/jama.2023.3954 -
PloS One 2015Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given its unique ability to eradicate persister bacilli. The worldwide burden of PZA resistance remains poorly described.
METHODS
Systematic PubMed, Science Direct and Scopus searches for articles reporting phenotypic (liquid culture drug susceptibility testing or pyrazinamidase activity assays) and/or genotypic (polymerase chain reaction or DNA sequencing) PZA resistance. Global and regional summary estimates were obtained from random-effects meta-analysis, stratified by presence or risk of multidrug resistant TB (MDR-TB). Regional summary estimates were combined with regional WHO TB incidence estimates to determine the annual burden of PZA resistance. Information on single nucleotide polymorphisms (SNPs) in the pncA gene was aggregated to obtain a global summary.
RESULTS
Pooled PZA resistance prevalence estimate was 16.2% (95% CI 11.2-21.2) among all TB cases, 41.3% (29.0-53.7) among patients at high MDR-TB risk, and 60.5% (52.3-68.6) among MDR-TB cases. The estimated global burden is 1.4 million new PZA resistant TB cases annually, about 270,000 in MDR-TB patients. Among 1,815 phenotypically resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout the pncA gene.
INTERPRETATION
PZA resistance is ubiquitous, with an estimated one in six incident TB cases and more than half of all MDR-TB cases resistant to PZA globally. The diversity of SNPs across the pncA gene complicates the development of rapid molecular diagnostics. These findings caution against relying on PZA in current and future TB drug regimens, especially in MDR-TB patients.
Topics: Antitubercular Agents; Humans; Mycobacterium tuberculosis; Pyrazinamide; Tuberculosis, Multidrug-Resistant
PubMed: 26218737
DOI: 10.1371/journal.pone.0133869 -
Pediatrics Jul 2015Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and... (Review)
Review
BACKGROUND
Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region.
METHODS
We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis.
RESULTS
We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120,872 (95% CI 96,628 to 149,059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%).
CONCLUSIONS
The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes.
Topics: Antitubercular Agents; Global Health; Humans; Incidence; Isoniazid; Tuberculosis, Multidrug-Resistant
PubMed: 26034243
DOI: 10.1542/peds.2015-0172 -
The Indian Journal of Tuberculosis Oct 2023Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The... (Review)
Review
INTRODUCTION
Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol.
MATERIALS AND METHODS
We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review.
RESULTS
Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment.
DISCUSSION
ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management.
CONCLUSION
This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.
Topics: Humans; Rifampin; Antitubercular Agents; Pyrazinamide; Isoniazid; Thrombocytopenia
PubMed: 37968056
DOI: 10.1016/j.ijtb.2023.04.029 -
The European Respiratory Journal Dec 2012Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on... (Meta-Analysis)
Meta-Analysis Review
Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤ 600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.
Topics: Acetamides; Adolescent; Adult; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Female; Humans; Linezolid; Male; Middle Aged; Oxazolidinones; Patient Safety; Sputum; Treatment Outcome; Tuberculosis, Multidrug-Resistant
PubMed: 22496332
DOI: 10.1183/09031936.00022912 -
The International Journal of... Jun 2016Therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes, but there is little evidence to guide TDM in clinical practice. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes, but there is little evidence to guide TDM in clinical practice.
DESIGN
We performed a systematic review and meta-analysis to summarise existing literature on TDM in first-line drugs.
RESULTS
We identified 41 studies that reported 2 h post-dose drug concentrations (C2h) for first-line drugs and 12 studies that reported clinical outcomes. We pooled data by study quality, design, region, dosing modality and patient characteristics. The pooled proportion of subjects with low isoniazid C2h was 0.43 (95%CI 0.32-0.55), 0.67 (95%CI 0.60-0.74) had low rifampicin C2h, 0.27 (95%CI 0.17-0.38) had low ethambutol C2h, and 0.12 (95%CI 0.07-0.19) had low pyrazinamide C2h. Patients with diabetes had a non-significant increase in the proportion of subjects with low C2h levels across all four drugs. Only three of 12 studies that examined clinical outcomes demonstrated an association between low C2h and unsuccessful treatment outcomes.
CONCLUSION
Across a wide variety of studies, a high proportion of patients undergoing first-line anti-tuberculosis treatment had 2 h drug concentrations below the accepted normal threshold. These findings point to a discrepancy between accepted 2 h TDM thresholds and TB drug dosing recommendations.
Topics: Antitubercular Agents; Databases, Factual; Dose-Response Relationship, Drug; Drug Monitoring; Ethambutol; Humans; Isoniazid; Pyrazinamide; Randomized Controlled Trials as Topic; Rifampin; Treatment Outcome; Tuberculosis
PubMed: 27155187
DOI: 10.5588/ijtld.15.0803