ethionamide and Tuberculosis

Tuberculosis, a disease of poverty is a communicable infection with a reasonably high mortality rate worldwide. 10 Million new cases of TB were reported with approx 1.4 million deaths in the year 2019. Due to the growing number of drug-sensitive and drug-resistant tuberculosis cases, there is a vital need to develop new and effective candidates useful to combat this deadly disease. Despite tremendous efforts to identify a mechanism-based novel antitubercular agent, only a few have entered into clinical trials in the last six decades. In recent years, triazoles have been well explored as the most valuable scaffolds in drug discovery and development. Triazole framework possesses favorable properties like hydrogen bonding, moderate dipole moment, enhanced water solubility, and also the ability to bind effectively with biomolecular targets of M. tuberculosis and therefore this scaffold displayed excellent potency against TB. This review is an endeavor to summarize an up-to-date innovation of triazole-appended hybrids during the last 10 years having potential in vitro and in vivo antitubercular activity with structure activity relationship analysis. This review may help medicinal chemists to explore the triazole scaffolds for the rational design of potent drug candidates having better efficacy, improved selectivity and minimal toxicity so that these hybrid NCEs can effectively be explored as potential lead to fight against M. tuberculosis.

Topics: Antitubercular Agents; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Structure-Activity Relationship; Triazoles; Tuberculosis

Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good

Topics: Antitubercular Agents; COVID-19 Drug Treatment; Drug Discovery; Humans; Mycobacterium tuberculosis; Tuberculosis

Tuberculosis (TB) remains one of the most widespread and leading deadliest diseases, threats one-third of the world's population. Although numerous efforts have been undertaken to develop new anti-TB agents, only a handful of compounds have entered human trials in the past 5 decades. Triazoles including 1,2,3-triazole and 1,2,4-triazole are one of the most important classes of nitrogen containing heterocycles that exhibited various biological activities. Triazole derivatives are regarded as a new class of effective anti-TB candidates owing to their potential anti-TB potency. Thus, molecules containing triazole moiety may show promising in vitro and in vivo anti-TB activities and might be able to prevent the drug resistant to certain extent. This review outlines the advances in the application of triazole-containing hybrids as anti-TB agents, and discusses the structure-activity relationship of these derivatives.

Topics: Antitubercular Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Structure-Activity Relationship; Triazoles; Tuberculosis

Fragment-based drug discovery is now widely used in academia and industry to obtain small molecule inhibitors for a given target and is established for many fields of research including antimicrobials and oncology. Many molecules derived from fragment-based approaches are already in clinical trials and two - vemurafenib and venetoclax - are on the market, but the approach has been used sparsely in the tuberculosis field. Here, we describe the progress of our group and others, and examine the most recent successes and challenges in developing compounds with antimycobacterial activity.

Topics: Animals; Antitubercular Agents; Bacterial Proteins; Cell Wall; Coenzyme A; Drug Design; Ethionamide; Humans; Mycobacterium tuberculosis; Repressor Proteins; Structure-Activity Relationship; Tuberculosis

Ethionamide (ETH) and prothionamide (PTH), both thioamides, have proven efficacy in clinical studies and form important components for multidrug-resistant tuberculosis treatment regimens and for treatment of tuberculous meningitis in adults and children. ETH and PTH are pro-drugs that, following enzymatic activation by mycobacterial EthA inhibit InhA, a target shared with isoniazid (INH), and subsequently inhibit mycolic acid synthesis of Mycobacterium tuberculosis. Co-resistance to INH and ETH is conferred by mutations in the mycobacterial inhA promoter region; mutations in the ethA gene often underlie ETH and PTH monoresistance. An oral daily dose of ETH or PTH of 15-20 mg/kg with a maximum daily dose of 1000 mg is recommended in children to achieve adult-equivalent serum concentrations shown to be efficacious in adults, although information on optimal pharmacodynamic targets is still lacking. Gastrointestinal disturbances, and hypothyroidism during long-term therapy, are frequent adverse effects observed in adults and children, but are rarely life-threatening and seldom necessitate cessation of ETH therapy. More thorough investigation of the therapeutic effects and toxicity of ETH and PTH is needed in childhood TB while child-friendly formulations are needed to appropriately dose children.

Topics: Adolescent; Age Factors; Animals; Antitubercular Agents; Child; Child, Preschool; Drug Compounding; Drug Dosage Calculations; Drug Resistance, Bacterial; Ethionamide; Humans; Infant; Mycobacterium tuberculosis; Prothionamide; Treatment Outcome; Tuberculosis; Young Adult

Currently, one third of the world's population is infected with Mycobacterium tuberculosis and 8.9-9.9 million new and relapse cases of tuberculosis are reported every year. The emergence of new cases, the increased incidence of multi-drug resistant strains of M. tuberculosis, and the adverse effects of first- and second-line antituberculosis drugs have led to renewed research interest in natural products in the hope of discovering new antitubercular leads. Interestingly, hundreds of natural products, possessing novel, uncommon, and known structural architectures, have been reported to exhibit activity towards non-resistant and multi-drug resistant strains of M. tuberculosis. The present review covers literature published during the last five years about those naturally occurring compounds with reported growth inhibitory activity in vitro towards sensitive and resistant M. tuberculosis strains. Compounds with antitubercular properties at minimal inhibitory concentrations (MICs) of less than 50 μg/mL or 60 μM were selected and grouped according to their source of origin (plants, bacteria, fungi, marine organisms, etc) and chemical type (terpenes, steroids, alkaloids, flavonoids, poliketides, peptides, etc). In some cases, the selection covers those structurally relevant natural products with low bioactivity (MICs of ≤128 μg/mL), and also those semisynthetic derivatives with remarkable antitubercular activity (MICs of ≤10 μg/mL). Additionally, this review includes a special section for those natural products that specifically target genes or enzymes of M. tuberculosis.

Topics: Animals; Antitubercular Agents; Biological Products; Drug Resistance, Multiple, Bacterial; Genes, Bacterial; Humans; Mycobacterium tuberculosis; Tuberculosis

A new class of antibacterials, diarylquinolines, was identified. The lead compound, R207910 (TMC207), was able to inhibit Mycobacterium tuberculosis in vitro, in mice and in patients. R207910 targets the mycobacterial ATP synthase. In vitro, it displayed potent activities against both drug-sensitive and multidrug-resistant strains of M. tuberculosis. It was also strongly active against dormant bacilli in the Wayne's dormancy culture system, hypoxia and nitric oxide models. In the murine model, when used alone, it was as active as the triple combination of rifampicin+isoniazid+pyrazinamide. When added to the previous combination or substituted for isoniazid or rifampicin, the treatment including the combinations containing R207910 led to culture conversion after 2 months of therapy. When added to the combination used to treat MDR-TB or substituted for moxifloxacin or ethionamide, the combinations containing R207910 led to culture conversion after 2 months of therapy. In MDR-TB infected patients, R207910 combined with second line drugs was able to convert more sputum cultures (47.6%) than the placebo combined to second line drugs regimen (8.7%).

Topics: Animals; Anti-Infective Agents; Antitubercular Agents; Aza Compounds; Diarylquinolines; Disease Models, Animal; Drug Therapy, Combination; Enzyme Inhibitors; Ethionamide; Fluoroquinolones; Humans; Mice; Moxifloxacin; Mycobacterium tuberculosis; Placebos; Quinolines; Tuberculosis

Topics: Animals; Antitubercular Agents; Ethionamide; Humans; Treatment Outcome; Tuberculosis

Topics: Antitubercular Agents; Drug Therapy, Combination; Ethionamide; Fatty Acids; Humans; Isoniazid; Liver; Malates; Metabolic Diseases; Mitochondria; Oxidative Phosphorylation; Rifampin; Succinates; Succinic Acid; Tuberculosis

Topics: Adult; Aminosalicylic Acids; Capreomycin; Child; Cycloserine; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Middle Aged; Mycobacterium tuberculosis; Pyrazinamide; Rifampin; Streptomycin; Time Factors; Tuberculosis; Viomycin

Topics: Antitubercular Agents; Drug Resistance, Microbial; Drug Therapy, Combination; Ethambutol; Ethionamide; Follow-Up Studies; Humans; Isoniazid; Pyrazinamide; Rifampin; Sputum; Streptomycin; Thioacetazone; Time Factors; Tuberculosis

Topics: Aminosalicylic Acids; Antitubercular Agents; Capreomycin; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Microbial; Ethambutol; Ethionamide; Germany, West; Humans; Isoniazid; Length of Stay; Rifampin; Streptomycin; Tuberculosis

Topics: Ambulatory Care; Anti-Bacterial Agents; Antitubercular Agents; Drug Synergism; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Peptides; Pyrazinamide; Thioacetazone; Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Urogenital; Viomycin

Topics: Aminosalicylic Acids; Animals; Cycloserine; Drug Hypersensitivity; Drug Resistance, Microbial; Ethionamide; Geography; Guinea Pigs; Hematopoietic System; Humans; Isoniazid; Mice; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Skin Manifestations; Streptomycin; Thioacetazone; Tuberculosis

Topics: Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Drug Synergism; Ethambutol; Ethionamide; Humans; Isoniazid; Phenylthiourea; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis

Topics: Aminosalicylic Acids; Animals; Bacteria; Drug Resistance, Microbial; Ethionamide; Guinea Pigs; Humans; Isoniazid; Phenylthiourea; Rabbits; Solubility; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Renal

Topics: Antitubercular Agents; Cycloserine; Ethionamide; Humans; Phenylthiourea; Pyrazinamide; Thiosemicarbazones; Tuberculosis; Viomycin

Topics: Antitubercular Agents; Ethionamide; Nervous System Diseases; Neurology; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Ethionamide; Isoniazid; Kanamycin; Mycobacterium tuberculosis; Phenylthiourea; Pyrazinamide; Serologic Tests; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Urogenital; Urine

Topics: Animals; Clinical Trials as Topic; Dose-Response Relationship, Drug; Ethionamide; Humans; Male; Rats; Thyroid Gland; Thyroid Hormones; Thyrotropin; Tuberculosis

Topics: Adolescent; Adult; Aged; Aminosalicylic Acids; Child, Preschool; Clinical Trials as Topic; Cycloserine; Diabetes Mellitus; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Liver Cirrhosis; Male; Mycoplasma Infections; Pregnancy; Streptomycin; Tuberculosis; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in many high tuberculosis (TB) burden countries. Phenotypic drug susceptibility testing (DST) take several weeks or months to result, but line probe assays and Xpert/Rif Ultra assay detect a limited number of resistance conferring gene mutations. Whole genome sequencing (WGS) is an advanced molecular testing method which theoretically can predict the resistance of M. tuberculosis (Mtb) isolates to all anti-TB agents through a single analysis.. Here, we aimed to identify the level of concordance between the phenotypic and WGS-based genotypic drug susceptibility (DS) patterns of MDR-TB isolates. Overall, data for 12 anti-TB medications were analyzed.. In total, 63 MDR-TB Mtb isolates were included in the analysis, representing 27.4% of the total number of MDR-TB cases in Latvia in 2012-2014. Among them, five different sublineages were detected, and 2.2.1 (Beijing group) and 4.3.3 (Latin American-Mediterranean group) were the most abundant. There were 100% agreement between phenotypic and genotypic DS pattern for isoniazid, rifampicin, and linezolid. High concordance rate (> 90%) between phenotypic and genotypic DST results was detected for ofloxacin (93.7%), pyrazinamide (93.7%) and streptomycin (95.4%). Phenotypic and genotypic DS patterns were poorly correlated for ethionamide (agreement 56.4%), ethambutol (85.7%), amikacin (82.5%), capreomycin (81.0%), kanamycin (85.4%), and moxifloxacin (77.8%). For capreomycin, resistance conferring mutations were not identified in several phenotypically resistant isolates, and, in contrary, for ethionamide, ethambutol, amikacin, kanamycin, and moxifloxacin the resistance-related mutations were identified in several phenotypically sensitive isolates.. WGS is a valuable tool for rapid genotypic DST for all anti-TB agents. For isoniazid and rifampicin phenotypic DST potentially can be replaced by genotypic DST based on 100% agreement between the tests. However, discrepant results for other anti-TB agents limit their prescription based solely on WGS data. For clinical decision, at the current level of knowledge, there is a need for combination of genotypic DST with modern, validated phenotypic DST methodologies for those medications which did not showed 100% agreement between the methods.

Topics: Amikacin; Antitubercular Agents; Capreomycin; Drug Resistance, Multiple, Bacterial; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Latvia; Microbial Sensitivity Tests; Moxifloxacin; Mycobacterium tuberculosis; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant; Whole Genome Sequencing

The WHO End TB Strategy requires drug susceptibility testing and treatment of all people with tuberculosis, but second-line diagnostic testing with line-probe assays needs to be done in experienced laboratories with advanced infrastructure. Fewer than half of people with drug-resistant tuberculosis receive appropriate treatment. We assessed the diagnostic accuracy of the rapid Xpert MTB/XDR automated molecular assay (Cepheid, Sunnyvale, CA, USA) to overcome these limitations.. We did a prospective study involving individuals presenting with pulmonary tuberculosis symptoms and at least one risk factor for drug resistance in four sites in India (New Delhi and Mumbai), Moldova, and South Africa between July 31, 2019, and March 21, 2020. The Xpert MTB/XDR assay was used as a reflex test to detect resistance to isoniazid, fluoroquinolones, ethionamide, amikacin, kanamycin, and capreomycin in adults with positive results for Mycobacterium tuberculosis complex on Xpert MTB/RIF or Ultra (Cepheid). Diagnostic performance was assessed against a composite reference standard of phenotypic drug-susceptibility testing and whole-genome sequencing. This study is registered with ClinicalTrials.gov, number NCT03728725.. Of 710 participants, 611 (86%) had results from both Xpert MTB/XDR and the reference standard for any drug and were included in analysis. Sensitivity for Xpert MTB/XDR detection of resistance was 94% (460 of 488, 95% CI 92-96) for isoniazid, 94% (222 of 235, 90-96%) for fluoroquinolones, 54% (178 of 328, 50-61) for ethionamide, 73% (60 of 82, 62-81) for amikacin, 86% (181 of 210, 81-91) for kanamycin, and 61% (53 of 87, 49-70) for capreomycin. Specificity was 98-100% for all drugs. Performance was equivalent to that of line-probe assays. The non-determinate rate of Xpert MTB/XDR (ie, invalid M tuberculosis complex detection) was 2·96%.. The Xpert MTB/XDR assay showed high diagnostic accuracy and met WHO's minimum target product profile criteria for a next-generation drug susceptibility test. The assay has the potential to diagnose drug-resistant tuberculosis rapidly and accurately and enable optimum treatment.. German Federal Ministry of Education and Research through KfW, Dutch Ministry of Foreign Affairs, and Australian Department of Foreign Affairs and Trade.

Topics: Adult; Amikacin; Australia; Capreomycin; Cross-Sectional Studies; Drug Resistance, Bacterial; Ethionamide; Fluoroquinolones; Humans; Isoniazid; Kanamycin; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Prospective Studies; Rifampin; Sensitivity and Specificity; Sputum; Tuberculosis; Tuberculosis, Multidrug-Resistant

Tuberculosis is an ancient disease of mankind, and its causative bacterium is Mycobacterium tuberculosis. Isoniazid is one of the most effective first-line antituberculosis drugs. As prodrugs, it and its derivative ethionamide act on enoyl-acyl carrier protein reductase (InhA) after being oxidized in bacteria, and kill the bacteria by inhibiting the formation of M. tuberculosis cell walls. However, the S94A mutation of InhA causes M. tuberculosis to develop cross-resistance to isoniazid and ethionamide. This work is dedicated to studying the cross-resistance mechanism of isoniazid and ethionamide through theoretical calculations. First, thermodynamic integral simulations are used to accurately calculate the relative binding energy of two drugs in the mutant and wild-type system. Furthermore, through classic molecular dynamic simulations and molecular mechanics generalized-Born surface area calculation, some key residues are identified and the binding affinity of isoniazid and ethionamide reduced by 9-13 kcal/mol due to S94A mutation. The hydrogen bond between Ala94 and isoniazid (ethionamide) disappeared and the energy contribution of Ala94 decreased after the mutation. In addition, the dynamic network analysis indicated that the mutation of Ser94 also indirectly affected the conformation of key residues such as Met147, Thr196, and Leu97, resulting in a reduction in the energy contribution of these residues. Finally, the binding conformation of isoniazid and ethionamide has also undergone major changes. The obtained results could provide valuable information for the future molecular design to overcome the drug resistance.

Topics: Bacterial Proteins; Ethionamide; Humans; Isoniazid; Molecular Dynamics Simulation; Mutation; Mycobacterium tuberculosis; Oxidoreductases; Thermodynamics; Tuberculosis

Topics: Acneiform Eruptions; Drug Eruptions; Ethionamide; Humans; Tuberculosis

The sensitivity of

Topics: Animals; Antitubercular Agents; Ethionamide; Mice; Mycobacterium tuberculosis; Prodrugs; Tuberculosis

Despite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against drug resistant TB. Over the same period, significant technological advances and learnings around target value have taken place. This has offered opportunities to re-assess the potential for optimization of previously discovered chemical matter against

Topics: Antitubercular Agents; beta-Lactams; Ethionamide; Humans; Spectinomycin; Tuberculosis; Tuberculosis, Multidrug-Resistant

Ethionamide (ETH) is a high-profile drug for the treatment of patients with multidrug-resistant

Topics: Antitubercular Agents; Binding Sites; Density Functional Theory; Ethionamide; Humans; Ligands; Molecular Dynamics Simulation; Mycobacterium tuberculosis; Repressor Proteins; Tuberculosis

Antibiotic resistance is a global challenge for tuberculosis control, and accelerating its diagnosis is critical for therapy decisions and controlling transmission. Genotype-based molecular diagnostics now play an increasing role in accelerating the detection of such antibiotic resistance, but their accuracy depends on the instructed detection of genetic variations. Genetic mobile elements such as IS

Topics: Antitubercular Agents; Clofazimine; Computational Biology; DNA Transposable Elements; Drug Resistance, Bacterial; Ethionamide; Humans; Mutation; Mycobacterium tuberculosis; Tuberculosis

Killing more than one million people each year, tuberculosis remains the leading cause of death from a single infectious agent. The growing threat of multidrug-resistant strains of

Topics: Animals; Antitubercular Agents; Crystallography, X-Ray; Drug Design; Drug Discovery; Ethionamide; Female; Mice; Mice, Inbred BALB C; Mycobacterium tuberculosis; Oxadiazoles; Repressor Proteins; Structure-Activity Relationship; Tuberculosis

The widely used second-line antituberculosis drug ethionamide shows wide interindividual variability in its disposition; however, the relevant factors affecting this phenomenon have not been characterized. We previously reported the major contribution of flavin-containing monooxygenase 3 (FMO3) in the reductive elimination pathway of ethionamide. In this study, ethionamide metabolism was potentially inhibited by methimazole in vitro. The drug-drug interaction leading to methimazole affecting the disposition of ethionamide mediated by FMO3 was then quantitated using a bottom-up approach with a physiologically based pharmacokinetic framework. The maximum concentration (C

Topics: Adult; Antitubercular Agents; Biological Variation, Population; Drug Interactions; Ethionamide; Female; Humans; Liver; Male; Methimazole; Models, Biological; Mutation; Oxygenases; Polymorphism, Genetic; Tuberculosis

Little is known about the metabolic state of

Topics: Adenosine Triphosphatases; Amides; Amino Acids; Antitubercular Agents; Cycloserine; Diarylquinolines; Drug Tolerance; Ethambutol; Ethionamide; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Humans; Isoniazid; Isoxazoles; Metabolic Networks and Pathways; Models, Biological; Mycobacterium bovis; Mycobacterium tuberculosis; Oxazolidinones; Spiro Compounds; Thiazines; Tuberculosis

Tuberculosis patients taking second line drugs such as ethionamide (ETH) have often experienced previous treatment failure and usually have a complex history of disease and treatment that can span decades. Mutations in the ETH activating enzyme, EthA, confer resistance through undescribed mechanisms. To explore the impact of EthA mutations on ETH resistance, data from a total of 160 ETH

Topics: Antitubercular Agents; Binding Sites; DNA, Bacterial; Drug Resistance, Bacterial; Ethionamide; Genetic Loci; Genotype; Humans; Mutation; Mycobacterium tuberculosis; Oxidoreductases; Phenotype; Protein Binding; Protein Conformation; Repressor Proteins; Structure-Activity Relationship; Tuberculosis

Topics: Animals; Antibiotics, Antitubercular; Drug Resistance, Bacterial; Ethionamide; Humans; Isoxazoles; Mice; Mycobacterium tuberculosis; Oxidoreductases; Prodrugs; Repressor Proteins; Spiro Compounds; Tuberculosis

A major limitation in current molecular docking method is that of failure to account for receptor flexibility. Herein we report multiple receptor conformers based molecular docking as a practical alternative to account for the receptor flexibility. Multiple (forty) conformers of Mycobacterium Enoyl ACP Reductase (InhA) are generated from Molecular Dynamics simulation and twenty crystallographic structures of InhA bound to different inhibitors are obtained from the Protein Data Bank. Fluorine directed modifications are performed to currently available anti-tuberculosis drug ethionamide. The modified drugs are optimized using B3LYP 6-31G (d,p) level of theory. Dipole moment, frontier orbital gap and thermodynamical properties such as electronic energy, enthalpy and Gibbs free energy of these optimized drugs are investigated. These drugs are subsequently docked against the conformers of InhA. Molecular docking against multiple InhA conformations show variation in ligand binding affinity and suggest that Ser94, Gly96, Lys165 and Ile194 amino acids play critical role on strong drug-InhA interaction. Modified drug N1 showed greater binding affinity compared to EN in most conformations. Structure of PDB ID: 2NSD and snapshot conformer at 5.5ns show most favorable binding with N1 compared to other conformers. Fluorine participates in forming fluorine bonds and contributes significantly in increasing binding affinity. Our study reveal that addition of trifluoromethyl group explicitly shows promise in improving thermodynamic properties and in enhancing hydrogen bonding and non-bonded interactions. Molecular dynamics (MD) simulation show that EN and N1 remained in the binding pocket similar to the docked pose of EN-InhA and E1-InhA complexes and also suggested that InhA binds to its inhibitor in inhibitor-induced folding manner. ADMET calculations predict modified drugs to have improved pharmacokinetic properties. Our study concludes that multiple receptor conformers based molecular docking can be an alternative to study the effect of receptor flexibility in ligand binding and fluorine directed modifications can improve drug efficacy.

Topics: Antitubercular Agents; Bacterial Proteins; Binding Sites; Drug Design; Ethionamide; Fluorine; Humans; Hydrogen Bonding; Molecular Docking Simulation; Molecular Dynamics Simulation; Mycobacterium tuberculosis; Oxidoreductases; Protein Binding; Protein Conformation; Thermodynamics; Tuberculosis

Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a transcriptional repressor that regulates the activation process of the antitubercular drug ethionamide (ETH) is a specific substrate of the mycobacterial kinase PknF. ETH is a prodrug that must undergo bioactivation by the monooxygenease EthA to exert its antimycobacterial activity and previous studies reported that EthR represses transcription of ethA by binding to the ethA-ethR intergenic region. Mass spectrometry analyses and site-directed mutagenesis identified a set of four phosphoacceptors, namely Thr2, Thr3, Ser4 and Ser7. This was further supported by the complete loss of PknF-dependent phosphorylation of a phosphoablative EthR mutant protein. Importantly, a phosphomimetic version of EthR, in which all phosphosites were replaced by Asp residues, exhibited markedly decreased DNA-binding activity compared with the wild-type protein. Together, these findings are the first demonstration of EthR phosphorylation and indicate that phosphorylation negatively affects its DNA-binding activity, which may impact ETH resistance levels in M. tb.

Topics: Amino Acid Sequence; Antitubercular Agents; Bacterial Proteins; Ethionamide; Humans; Molecular Sequence Data; Mutagenesis, Site-Directed; Mycobacterium tuberculosis; Phosphorylation; Protein Serine-Threonine Kinases; Repressor Proteins; Serine; Threonine; Tuberculosis

The emergence of drug-resistant, multidrug-resistant and extensively drug-resistant tuberculosis (TB) is of major public health concern in several countries. In this study, the pharmacodynamic relationships among the structural analogs of antibiotics belonging to the same family were taken into consideration. The aim of this study was to compare the susceptibility of Mycobacterium tuberculosis to isoniazid (INH), rifampicin and levofloxacin (LX) to their respective structural analogs, which are frequently used as second-line agents. The microplate colorimetric method was used to determine the MIC to INH, ethionamide (ETH), rifampicin, rifabutin, LX and moxifloxacin (MOX) in clinical isolates previously shown to be drug resistant. Mutations conferring drug resistance were detected by GenoType MTBDR plus and DNA sequencing. INH and ETH cross-resistance was found in 95.12% (39/41) of the INH-resistant isolates harboring a mutation in inhAP or inhA open reading frame, but rifabutin cross-resistance was observed in 90.0% (63/70) of the clinical isolates originally shown to be resistant to rifampicin. Isolates with high LX-resistance levels also showed high MIC to MOX. Fluoroquinolone cross-resistance was verified in isolates containing the gyrA94 and the gyrA90 mutation. In general, isolates with high INH, rifampicin and LX-resistance levels also displayed high MIC values for their structural analogs. These findings suggest the need to test in vitro the second-line drugs before their incorporation in the therapeutic schemes.

Topics: Antitubercular Agents; Base Sequence; Colorimetry; Drug Resistance, Bacterial; Ethionamide; Fluoroquinolones; Humans; Isoniazid; Levofloxacin; Microbial Sensitivity Tests; Moxifloxacin; Mutation; Mycobacterium tuberculosis; Open Reading Frames; Rifabutin; Rifampin; Sequence Analysis, DNA; Tuberculosis

It has been shown previously that fluoroquinolone resistance (defined by resistance to at least 2 mg/liter ofloxacin) has a different impact on moxifloxacin monotherapy depending on the mutation in the sole fluoroquinolone target in Mycobacterium tuberculosis, i.e., DNA gyrase. Since tuberculosis treatment relies on multidrug therapy, we wished to determine the impact of fluoroquinolone resistance on the bactericidal and sterilizing activity of a second-line antituberculous regimen containing moxifloxacin. A total of 280 mice were inoculated with the wild-type Mycobacterium tuberculosis H37Rv strain or one of 3 isogenic fluoroquinolone-resistant mutant strains with increasing moxifloxacin resistance (the GyrB D500N, GyrA A90V, and GyrA D94G strains) and then treated for 6 months with a second-line regimen containing moxifloxacin, pyrazinamide, and ethionamide supplemented with amikacin during the first 2 months. Mice were sacrificed during treatment for measurement of bactericidal activity and 3 months after treatment completion for measurement of relapse rates (sterilizing activity). The CFU counts decreased faster in mice inoculated with the wild type than in mice inoculated with the mutant strains. The relapse rate after treatment completion was different among mice inoculated with mutant strains in relation to the drug resistance level: wild type, 0%; GyrB D500N strain, 33%; GyrA A90V strain, 50%; and GyrA D94G strain, 86%. The relapse rate observed with the GyrB D500N strain was the only one not statistically different from that observed with the wild-type strain. We demonstrated that the impact on sterilizing activity of the most active second-line drug regimen containing moxifloxacin depends on the MIC of moxifloxacin. We suggest that the precise level of moxifloxacin resistance be determined for all strains resistant to 2 mg/liter ofloxacin.

Topics: Amikacin; Animals; Antitubercular Agents; Aza Compounds; DNA Gyrase; Drug Administration Schedule; Drug Resistance, Bacterial; Ethionamide; Female; Fluoroquinolones; Mice; Microbial Sensitivity Tests; Moxifloxacin; Mutation; Mycobacterium tuberculosis; Ofloxacin; Quinolines; Recurrence; Rodent Diseases; Survival Analysis; Tuberculosis

To determine the content of certain antituberculosis (TB) drugs supplied at TB treatment centres of the Revised National TB Control Programme (RNTCP) in the state of Tamil Nadu, India.. Eight districts across the state were selected, and the following drugs were collected from five settings (District TB centre, TB unit, designated microscopy centres, DOT providers) in each district: rifampicin (150 and 450 mg), isoniazid (300 mg), pyrazinamide (500 and 750 mg), ethambutol (400 and 600 mg), ethionamide (250 mg), levofloxacin (500 mg) and cycloserine (250 mg). A maximum of 10 tablets/capsules were collected from each setting. The drugs were coded prior to analysis. All drugs were assayed by validated spectrophotometric methods. The acceptable limits for drug content were taken as 90-110% of the stated content.. More than 90% of tablets of rifampicin 450 mg, isoniazid 300 mg, pyrazinamide 500 and 750 mg, ethambutol 400 and 600 mg and ethionamide 250 mg were within acceptable limits. Eighty per cent of rifampicin 150 mg, 21% of cycloserine 250 mg and 87% of levofloxacin 500 mg were within acceptable limits. The mean cycloserine content was below the acceptable limit in all districts, the mean drug content being 200 mg (range: 108-245 mg).. This systematic study showed that the stated drug content of cycloserine was not reached in all districts. Deterioration of cycloserine could be minimised by storing the drug in refrigerators. The geographical location of the districts had no influence on the drug content.

Topics: Antitubercular Agents; Cycloserine; Drug Stability; Drug Storage; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; India; Isoniazid; Levofloxacin; Ofloxacin; Pyrazinamide; Rifampin; Spectrophotometry; Tuberculosis

Various polycharged calix[4]arenes were assayed as anti-mycobacterial agents against Mycobacterium tuberculosis, H(37)Rv strain. The sulfonate, carboxylate and phosphonate anionic species displayed no activity. Cationic derivatives integrating four aminoethyl groups at the upper rim and two 6,6'-dimethyl-2,2'-bipyridyl- or 4,4'-dimethyl-2,2'-bithiazolyl subunits at the lower rim were also found inactive against M. tuberculosis, while the unsubstituded and the 5,5'-dimethyl-2,2'-bipyridyl-analogues exhibited MIC values of 3.2 and 0.8μM respectively. Introduction of guanidinoethyl groups at the upper rim resulted, except for the 6,6'-dimethyl-2,2'-bipyridyl-derivative, in high anti-mycobacterial activities for the unsubstituted, the 5,5'-dimethyl-2,2'-bipyridyl- and the 4,4'-dimethyl-2,2'-bithiazolyl analogues, with MIC values of 0.8, 0.8 and 1.6μM, respectively, similar to those of current commercial anti-tuberculosis agents. The five more active substances were also evaluated against the isoniazid-resistant strain MYC5165, resulting in highly interesting micromolar or sub-micromolar MIC and IC(50), ca. 4-125 times more active than isoniazid. These preliminary results are attractive for the development of new anti-TB agents.

Topics: 2,2'-Dipyridyl; Anions; Antitubercular Agents; Calixarenes; Guanidine; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Phenols; Quaternary Ammonium Compounds; Tuberculosis

Ethionamide (ETH), a second-line antituberculosis drug, is frequently used in treating childhood tuberculosis. Data supporting ETH dose recommendations in children are limited. The aim of this study was to determine the pharmacokinetic parameters for ETH in children on antituberculosis treatment including ETH. ETH serum levels were prospectively assessed in 31 children in 3 age groups (0 to 2 years, 2 to 6 years, and 6 to 12 years). Within each age group, half received rifampin (RMP). Following an oral dose of ETH (15 to 20 mg/kg of body weight), blood samples were collected at 0, 1, 2, 3, 4, and 6 h following 1 and 4 months of ETH therapy. The maximum serum concentration (C(max)), time to C(max) (T(max)), and area under the time-concentration curve from 0 to 6 h (AUC(0-6)) were calculated. Younger children were exposed to lower ETH concentrations than older children at the same mg/kg body weight dose. Age correlated significantly with the AUC after both 1 month (r = 0.50, P = 0.001) and 4 months (r = 0.63, P = 0.001) of therapy. There was no difference in the AUC or C(max) between children receiving concomitant treatment with RMP and those who did not. Time on treatment did not influence the pharmacokinetic parameters of ETH following 1 and 4 months of therapy. HIV infection was associated with lower ETH exposure. In conclusion, ETH at an oral dose of 15 to 20 mg/kg results in sufficient serum concentrations compared to current adult recommended levels in the majority of children across all age groups. ETH levels were influenced by young age and HIV status but were not affected by concomitant RMP treatment and duration of therapy.

Topics: Anti-HIV Agents; Antitubercular Agents; Child; Child, Preschool; Drug Therapy, Combination; Ethionamide; Female; HIV Infections; Humans; Infant; Male; Mycobacterium tuberculosis; Rifampin; Tuberculosis

Ethionamide (ETH) treatment may cause hypothyroidism. Clinical data, serum thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels were retrospectively assessed in 137 children receiving anti-tuberculosis treatment including ETH. Abnormal thyroid function tests (TFTs) were recorded in 79 (58%) children: elevated serum TSH and suppressed fT4 (n = 30), isolated elevated serum TSH (n = 20), isolated low serum fT4 (n = 28) and isolated low TSH (n = 1). The risk for biochemical hypothyroidism was higher for children on regimens including para-aminosalicylic acid and in human immunodeficiency virus infected children. TFT abnormalities are frequent in children on ETH and are mainly due to primary hypothyroidism or euthyroid sick syndrome.

Topics: Adolescent; Aminosalicylic Acid; Antitubercular Agents; Child; Child, Preschool; Ethionamide; Euthyroid Sick Syndromes; Female; HIV Infections; Humans; Hypothyroidism; Infant; Male; Retrospective Studies; Thyroid Function Tests; Thyrotropin; Thyroxine; Tuberculosis

The side effects associated with tuberculosis therapy bring with them the risk of noncompliance and subsequent drug resistance. Increasing the therapeutic index of antituberculosis drugs should thus improve treatment effectiveness. Several antituberculosis compounds require in situ metabolic activation to become inhibitory. Various thiocarbamide-containing drugs, including ethionamide, are activated by the mycobacterial monooxygenase EthA, the production of which is controlled by the transcriptional repressor EthR. Here we identify drug-like inhibitors of EthR that boost the bioactivation of ethionamide. Compounds designed and screened for their capacity to inhibit EthR-DNA interaction were co-crystallized with EthR. We exploited the three-dimensional structures of the complexes for the synthesis of improved analogs that boosted the ethionamide potency in culture more than tenfold. In Mycobacterium tuberculosis-infected mice, one of these analogs, BDM31343, enabled a substantially reduced dose of ethionamide to lessen the mycobacterial load as efficiently as the conventional higher-dose treatment. This provides proof of concept that inhibiting EthR improves the therapeutic index of thiocarbamide derivatives, which should prompt reconsideration of their use as first-line drugs.

Topics: Animals; Antitubercular Agents; Binding Sites; DNA-Binding Proteins; Drug Synergism; Ethionamide; Hydrogen Bonding; Ligands; Mice; Models, Molecular; Oxadiazoles; Protein Conformation; Repressor Proteins; Thiophenes; Tuberculosis

The Bactec MGIT 960 system for testing susceptibility to second-line drugs was evaluated with 117 clinical strains in a multicenter study. The four drugs studied were levofloxacin, amikacin, capreomycin, and ethionamide. The critical concentration established for levofloxacin and amikacin was 1.5 microg/ml, that established for capreomycin was 3.0 microg/ml, and that established for ethionamide was 5.0 microg/ml. The overall level of agreement between the agar proportion method and the MGIT 960 system was 96.4%, and the levels of agreement for the individuals drugs were 99.1% for levofloxacin, 100% for amikacin, 97.4% for capreomycin, and 88.9% for ethionamide. The rate of reproducibility of the drug susceptibility testing results between the participating laboratories was 99.5%.

Topics: Amikacin; Antitubercular Agents; Capreomycin; Ethionamide; Humans; Levofloxacin; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Ofloxacin; Reproducibility of Results; Sensitivity and Specificity; Tuberculosis

We reevaluated the BACTEC MGIT 960 antimicrobial susceptibility testing system (MGIT 960 AST) by using 1,112 isolates of Mycobacterium tuberculosis. When the results of MGIT 960 AST were compared with that of the proportion method using Ogawa medium (Ogawa PM), discrepant results were obtained for 30 strains with isoniazid, all resistant by MGIT 960 AST but susceptible by Ogawa PM. For 93% of the strains that produced discrepant results, the MIC was 0.4 or 0.8 microg/ml, showing resistance by the proportion method using Middlebrook agar plates. Furthermore, it was also established by analyses of the katG and inhA genes that strains resistant only by MGIT 960 AST have a low level of isoniazid (INH) resistance, indicating that MGIT 960 AST is a reliable method. Ninety-six strains were resistant to 0.1 microg/ml INH by MGIT 960 AST. When they were divided into three groups, Low-S (susceptible at 0.2 microg/ml), Low-R (resistant at 0.2 microg/ml), and High-R (resistant at 1.0 microg/ml), by Ogawa PM, 43.3% of the Low-S strains had mutations in the promoter region of inhA and no mutations were detected in katG codon 315, while 61.7% of the High-R strains had katG codon 315 mutations or a gross deletion of katG. These results suggest that mutations in inhA are associated with low-level resistance to INH and katG codon 315 mutations are associated with high-level resistance to INH. In addition, the analyses demonstrated some relationship of mutations in the inhA gene with ethionamide resistance for the Low-S strains, but not for the High-R strains.

Topics: Antitubercular Agents; Bacterial Proteins; Catalase; Codon, Nonsense; DNA, Bacterial; Drug Resistance, Bacterial; Ethionamide; Gene Deletion; Humans; Isoniazid; Japan; Microbial Sensitivity Tests; Mutation; Mutation, Missense; Mycobacterium tuberculosis; Oxidoreductases; Promoter Regions, Genetic; Tuberculosis

Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections. Although generally considered second-line drugs for tuberculosis, their use has increased considerably as the number of multidrug resistant and extensively drug resistant tuberculosis cases continues to rise. Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy, their precise mechanisms of action remain unknown. Using a cell-based activation method, we now have definitive evidence that both thioamides form covalent adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the molecular details of target-drug interactions. The purified ETH-NAD and PTH-NAD adducts both showed nanomolar Kis against M. tuberculosis and M. leprae InhA. Knowledge of the precise structures and mechanisms of action of these drugs provides insights into designing new drugs that can overcome drug resistance.

Topics: Antitubercular Agents; Bacterial Proteins; Crystallography, X-Ray; Drug Design; Drug Resistance, Multiple, Bacterial; Ethionamide; Humans; In Vitro Techniques; Leprostatic Agents; Leprosy; Models, Molecular; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium leprae; Mycobacterium tuberculosis; NAD; Oxidoreductases; Prothionamide; Tuberculosis; Tuberculosis, Multidrug-Resistant

The objective of the present study was to identify the optimal R207910-containing regimen to administer to patients who cannot receive rifampin (RIF) and isoniazid (INH) because of multidrug-resistant tuberculosis (MDR-TB), concomitant use of antiretroviral drugs, or toxicity. Mice were infected intravenously with 5 x 10(6) CFU of the H37Rv strain and treated five times per week with R207910 alone or various combinations of R207910 with the second-line drugs amikacin (AMK), pyrazinamide (PZA), moxifloxacin (MXF), and ethionamide (ETH). All R207910-containing regimens were significantly more active than the non-R207910-containing regimens after 1 month of therapy. When given for 2 months, R207910 alone was more active than the WHO standard first-line regimen RIF-INH-PZA. When R207910 was combined with second-line drugs, the combinations were more active than the currently recommended regimen of MDR-TB AMK-ETH-MXF-PZA, and culture negativity of both the lungs and spleen was reached after 2 months of treatment in almost every case.

Topics: Animals; Anti-Bacterial Agents; Antitubercular Agents; Aza Compounds; Colony Count, Microbial; Diarylquinolines; Drug Combinations; Drug Resistance, Multiple, Bacterial; Ethionamide; Fluoroquinolones; Lung; Mice; Moxifloxacin; Mycobacterium tuberculosis; Organ Size; Pyrazinamide; Quinolines; Rifampin; Spleen; Survival Analysis; Tuberculosis

Topics: Antitubercular Agents; Ethionamide; Humans; Tuberculosis

The incidence and pattern of extrathoracic tuberculosis in the Siberian and Far Eastern areas are analyzed. The statements are illustrated by two clinical cases.

Topics: Adult; Antitubercular Agents; Catchment Area, Health; Ethionamide; Female; Humans; Male; Middle Aged; Mycobacterium Infections; Russia; Skin Diseases; Tuberculosis

The use of gatifloxacin (GAT) in combination with ethionamide (ETA) with or without pyrazinamide (PZA) for a 12-week treatment period followed by an 8-week observation period was evaluated in a model of tuberculosis in mice. Mice treated with GAT at 300 mg/kg of body weight in combination with ETA (25 mg/kg) for 5 days per week had sterile lungs, whereas mice treated with GAT (100 mg/kg) and ETA (25 mg/kg) had about 10 CFU/lung; however, there was regrowth of the organisms in both groups at the end of the observation period. When PZA (450 mg/kg 5 days per week) was added to the high-dose GAT-ETA regimen, no viable mycobacteria were present after the 8-week observation period. GAT in combination with ETA and PZA has great promise for the treatment of tuberculosis.

Topics: Administration, Intranasal; Animals; Anti-Infective Agents; Antitubercular Agents; Colony-Forming Units Assay; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Ethionamide; Female; Fluoroquinolones; Gatifloxacin; Lung; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Tuberculosis

Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-pyridylmethanol product remarkably similar in structure to that formed by the activation of isoniazid by the catalase-peroxidase KatG. We have demonstrated that overproduction of Rv3855 (EtaR), a putative regulatory protein from MTb, confers ETA resistance whereas overproduction of an adjacent, clustered monooxygenase (Rv3854c, EtaA) confers ETA hypersensitivity. Production of EtaA appears to be negatively regulated by EtaR and correlates directly with [(14)C]ETA metabolism, suggesting that EtaA is the activating enzyme responsible for thioamide oxidation and subsequent toxicity. Coding sequence mutations in EtaA were found in 11 of 11 multidrug-resistant MTb patient isolates from Cape Town, South Africa. These isolates showed broad cross-resistance to thiocarbonyl containing drugs including ETA, thiacetazone, and thiocarlide.

Topics: Amino Acid Substitution; Antitubercular Agents; Bacterial Proteins; Drug Resistance, Microbial; Drug Resistance, Multiple; Ethionamide; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Oxidation-Reduction; Thioamides; Tuberculosis

We report a case of an HIV-infected child with a second episode of tuberculosis 22 months after completing antituberculosis treatment. DNA fingerprinting of organisms from both episodes showed an identical strain of Mycobacterium tuberculosis. We believe this to be the first case of confirmed relapsed tuberculosis in an HIV-infected child, and suggest that a longer course of antituberculosis treatment be given to such children. ¿ 2000 The British Infection Society.

Topics: AIDS-Related Opportunistic Infections; Amoxicillin-Potassium Clavulanate Combination; Antibiotics, Antitubercular; Antitubercular Agents; Child, Preschool; DNA, Bacterial; Drug Therapy, Combination; Ethionamide; HIV; HIV Infections; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Polymorphism, Restriction Fragment Length; Pyrazinamide; Radiography, Thoracic; Rifampin; Secondary Prevention; South Africa; Tomography, X-Ray Computed; Tuberculin Test; Tuberculosis; Tuberculosis, Meningeal

In spring 1993, four students in a high school were diagnosed with tuberculosis resistant to isoniazid, streptomycin, and ethionamide.. To investigate potential transmission of drug-resistant tuberculosis, a retrospective cohort study with case investigation and screening by tuberculin skin tests and symptom checks was conducted in a high school of approximately 1400 students. Current and graduated high-school students were included in the investigation. DNA fingerprinting of available isolates was performed.. Eighteen students with active tuberculosis were identified. Through epidemiologic and laboratory investigation, 13 cases were linked; 8 entered 12th grade in fall 1993; 9 of 13 had positive cultures for Mycobacterium tuberculosis with isoniazid, streptomycin, and ethionamide resistance, and all 8 available isolates had identical DNA fingerprints. No staff member had tuberculosis. One student remained infectious for 29 months, from January 1991 to June 1993, and was the source case for the outbreak. Another student was infectious for 5 months before diagnosis in May 1993 and was a treatment failure in February 1994 with development of rifampin and ethambutol resistance in addition to isoniazid, streptomycin, and ethionamide. In the fall 1993 screening, 292 of 1263 (23%) students tested had a positive tuberculin skin test. Risk of infection was highest among 12th graders and classroom contacts of the two students with prolonged infectiousness. An additional 94 of 928 (10%) students tested in spring 1994 had a positive tuberculin skin test; 22 were classroom contacts of the student with treatment failure and 21 of these had documented tuberculin skin test conversions.. Extensive transmission of drug-resistant tuberculosis was documented in this high school, along with missed opportunities for prevention and control of this outbreak. Prompt identification of tuberculosis cases and timely interventions should help reduce this public health problem.

Topics: Adolescent; California; Cohort Studies; Disease Outbreaks; Drug Resistance, Multiple; Ethambutol; Ethionamide; Female; Humans; Infectious Disease Transmission, Vertical; Isoniazid; Male; Mass Screening; Mycobacterium tuberculosis; Retrospective Studies; Rifampin; Schools; Skin Tests; Sputum; Streptomycin; Tuberculosis

Topics: Base Sequence; DNA Primers; DNA, Bacterial; Drug Resistance, Microbial; Drug Resistance, Multiple; Ethionamide; Genes, Bacterial; Humans; Isoniazid; Molecular Sequence Data; Mutation; Mycobacterium tuberculosis; Polymerase Chain Reaction; Tuberculosis

During 1990 and 1991, nosocomial transmission of multidrug-resistant tuberculosis (MDR-TB) was documented in four hospitals in New York and Florida. Subsequently, additional MDR-TB outbreaks have been investigated by CDC. This report summarizes preliminary results of an investigation of transmission of MDR-TB in a correctional facility in New York.

Topics: Antitubercular Agents; Drug Resistance, Microbial; Ethambutol; Ethionamide; HIV Seropositivity; Humans; Immunocompromised Host; Isoniazid; Kanamycin; Mycobacterium tuberculosis; New York; Prisons; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis

Topics: Antitubercular Agents; Drug Resistance, Microbial; Ethambutol; Ethionamide; HIV Seropositivity; Humans; Immunocompromised Host; Isoniazid; Kanamycin; Mycobacterium tuberculosis; New York; Prisons; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis

Drug resistance is a major problem in the treatment of tuberculosis, and monitoring programmes are essential in control of this disease. The extent of primary resistance in a community is an important indication of the effectiveness of treatment schedules. Since 1965 the Tuberculosis Research Institute (TBRI) of the South African Medical Research Council has performed 25 annual surveys of drug resistance in adult black tuberculosis patients where the disease is most prevalent. Methodology for patient selection, specimen collection, laboratory procedures and criteria for drug resistance were strictly adhered to. All specimens were processed in a central laboratory supervised by the same two technologists. Between 1965 and 1988 a total of 33,111 strains of Mycobacterium tuberculosis were isolated from new cases and 19,134 from old cases. Both primary and acquired resistance to the 5 major antituberculosis drugs has decreased dramatically. Sex and age do not influence resistance rates, while patients' ethnic origin and geographical location do. The results indicate that current tuberculosis treatment practices are satisfactory. The prevalence of primary drug resistance in black South Africans is now intermediate between those countries where eradication of tuberculosis is well advanced and those where the disease remains a public health problem. Also, it can be shown that comparable and clinically significant data can be obtained from a central laboratory employing unsophisticated and inexpensive drug susceptibility testing procedures.

Topics: Black or African American; Black People; Drug Resistance, Microbial; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Male; Mycobacterium tuberculosis; Rifampin; South Africa; Streptomycin; Tuberculosis

This study of tuberculous treatment in a French department--Les Hautes Pyrenees--was carried out on 539 patients registered on an epidemiological card index from 1973 to 1980. Isoniazid, ethambutol and rifampicin were the drugs most commonly used and were prescribed in 96% of cases by Specialists in thoracic medicine. The mean duration of treatment was a little more than 12 months for the duration of the study. A quarter of the patients were admitted to hospital and this figure did not change during the study from one year to the next although the mean length of stay fell by half between 1973 and 1980, the longest stays in hospital were for social reasons.

Topics: Ambulatory Care; Antitubercular Agents; Drug Therapy, Combination; Ethambutol; Ethionamide; Hospitalization; Humans; Isoniazid; Rifampin; Streptomycin; Tuberculosis

In a report on the extrapulmonary tuberculosis the abdominal forms are once more emphasized and analysed on the basis of a number of patients. There are no more any actual references to this picture of a disease in the modern general situation of tuberculosis, as by abolition of the bovine tuberculosis the prerequisites could be removed. There is no decisive symptomatology which leads to an abdominal tuberculosis. With the help of 89 clinically treated cases certain problems could be elaborated with regard to the diagnostics and therapy. The inclination to recidivation is not unconsiderable (8.9%), which is due to a disappointing bacteriological diagnostics and the false chemotherapeutic treatments resulting from this. With 34 cases in the GDR in 1976 this tuberculous disease is at present scarcely still of any significance. It must also in future be reckoned with sporadic new diseases which appear due to an intermittent lympho-haematogenic dissemination from tuberculous lung, pleura or lymph node processes and which may be treated with success by a modern multiple chemotherapy in a tuberculosis institution. The severe courses accompanied by complications which gave rise to surgical emergency measures might finally belong to the past.

Topics: Aftercare; Cycloserine; Ethambutol; Ethionamide; Gastrointestinal Diseases; Humans; Mesentery; Peritoneum; Pyrazinamide; Tuberculosis; Tuberculosis, Gastrointestinal; Tuberculosis, Hepatic; Tuberculosis, Lymph Node

Topics: Aminosalicylic Acids; Animals; Antitubercular Agents; Capreomycin; Chemical and Drug Induced Liver Injury; Cycloserine; Deafness; Drug Hypersensitivity; Ethambutol; Ethionamide; Gastrointestinal Diseases; Goiter; Humans; Isoniazid; Kanamycin; Liver; Mental Disorders; Mice; Nervous System Diseases; Pyrazinamide; Rifampin; Streptomycin; Thioacetazone; Tuberculosis; Viomycin

Topics: Aminosalicylic Acids; Capreomycin; Ethambutol; Ethionamide; Humans; Isoniazid; Prothionamide; Pyrazinamide; Rifampin; Streptomycin; Thioacetazone; Tuberculosis

Topics: Drug Resistance, Microbial; Ethionamide; Isoniazid; Microbial Sensitivity Tests; Mycobacterium; Senegal; Streptomycin; Thioacetazone; Tuberculosis

Topics: Amides; Aminosalicylic Acids; Antitubercular Agents; Capreomycin; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; Isoniazid; Isonicotinic Acids; Kanamycin; Phenylthiourea; Pyrazinamide; Rifampin; Streptomycin; Tetracycline; Thiosemicarbazones; Tuberculosis; Viomycin

Topics: Air Microbiology; Aminosalicylic Acids; Child; Child Day Care Centers; Child, Preschool; Disease Outbreaks; Environmental Exposure; Ethionamide; Female; Follow-Up Studies; Humans; Infant; Isoniazid; Lung; Male; Middle Aged; Mycobacterium tuberculosis; New Hampshire; Radiography; Streptomycin; Tuberculin Test; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adolescent; Adult; Ambulatory Care; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Ethionamide; Female; Humans; Isoniazid; Kanamycin; Male; Middle Aged; Moldova; Pyrazinamide; Rural Health; Streptomycin; Thiosemicarbazones; Tuberculosis

Topics: Aminosalicylic Acids; Antitubercular Agents; Arthritis; Chemical and Drug Induced Liver Injury; Child; Cycloserine; Drug Hypersensitivity; Drug Resistance, Microbial; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Liver; Lupus Vulgaris; Male; Middle Aged; Pyrazinamide; Rifampin; Streptomycin; Tuberculin Test; Tuberculosis; Viomycin

Topics: Administration, Oral; Adult; Aminosalicylic Acids; Antibody Formation; Antitubercular Agents; BCG Vaccine; Child; Child, Preschool; Drug Therapy, Combination; Ethambutol; Ethionamide; Humans; Immunity, Cellular; Infant; Isoniazid; Rifampin; Streptomycin; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary

Topics: Ambulatory Care; Aminosalicylic Acids; Antitubercular Agents; Capreomycin; Ethambutol; Ethionamide; Finland; Humans; Isoniazid; Patient Dropouts; Pyrazinamide; Rifampin; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aspartate Aminotransferases; Biopsy; Chemical and Drug Induced Liver Injury; Ethionamide; Follow-Up Studies; Humans; Liver; Long-Term Care; Necrosis; Pyrazinamide; Tuberculosis

Topics: Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Drug Hypersensitivity; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Pyrazinamide; Pyridoxine; Rifampin; Sputum; Streptomycin; Tuberculosis; Viomycin

Topics: Antitubercular Agents; Ethambutol; Ethionamide; Rifampin; Tuberculosis

Topics: Aminosalicylic Acids; Antitubercular Agents; Chemical and Drug Induced Liver Injury; Ethionamide; Humans; Isoniazid; Liver; Pyrazinamide; Streptomycin; Thioacetazone; Tuberculosis

Topics: Animals; Ethionamide; Growth; Guinea Pigs; Humans; Isoniazid; Rifampin; Streptomycin; Thioacetazone; Time Factors; Tuberculosis

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Antitubercular Agents; Body Weight; Ethambutol; Ethionamide; Injections, Intramuscular; Kanamycin; Lung; Mice; Organ Size; Pyrazinamide; Rifampin; Spleen; Tuberculosis; Viomycin

Topics: Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Depression, Chemical; Drug Resistance, Microbial; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Microbial Sensitivity Tests; Mycobacterium; Rifampin; Streptomycin; Thiosemicarbazones; Tuberculosis; Viomycin

Topics: Adult; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Drug Resistance, Microbial; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Kanamycin; Male; Microbial Sensitivity Tests; Middle Aged; Phenylthiourea; Pyrazinamide; Rifampin; Streptomycin; Thiosemicarbazones; Tuberculosis; Viomycin

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Disease Models, Animal; Ethionamide; Female; Fertility; Fetus; Gestational Age; Gonads; Infant Mortality; Kidney; Liver; Long-Term Care; Male; Mice; Pregnancy; Pregnancy, Prolonged; Sex Factors; Tuberculosis

Topics: Ambulatory Care; Aminosalicylic Acids; Drug Resistance; Ethionamide; Humans; Physician-Patient Relations; Tuberculosis

Topics: Administration, Oral; Animals; Drug Synergism; Ethambutol; Ethionamide; Female; Isoniazid; Mice; Mice, Inbred Strains; Rifampin; Tuberculosis

Topics: Animals; Cell Count; Chronic Disease; Disease Models, Animal; Drug Synergism; Ethambutol; Ethionamide; Isoniazid; Lung; Mice; Placebos; Rifampin; Streptomycin; Tuberculosis

Topics: Drug Resistance, Microbial; Ethionamide; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Phenylthiourea; Thioacetazone; Tuberculosis

Topics: Antitubercular Agents; Ethambutol; Ethionamide; Follow-Up Studies; Humans; Isoniazid; Long-Term Care; Male; Medication Errors; Middle Aged; Rifampin; Streptomycin; Tuberculosis

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Ethambutol; Ethionamide; Injections, Intravenous; Isoniazid; Kanamycin; Mice; Mycobacterium tuberculosis; Phenylthiourea; Streptomycin; Tuberculosis; Viomycin

Topics: Animals; Dinitrophenols; Ethionamide; Female; Isoniazid; Lung; Male; Mycobacterium tuberculosis; Time Factors; Tuberculosis

Topics: Cycloserine; Drug Resistance, Microbial; Ethambutol; Ethionamide; Female; Humans; Male; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Time Factors; Tuberculosis

Topics: Animals; Cycloserine; Drug Resistance, Microbial; Endopeptidases; Ethambutol; Ethionamide; Isoniazid; Kanamycin; Mice; Mycobacterium tuberculosis; Streptomycin; Sulfamethoxypyridazine; Tuberculosis

Topics: Animals; Drug Combinations; Drug Resistance, Microbial; Ethambutol; Ethionamide; Evaluation Studies as Topic; Isoniazid; Mice; Mycobacterium tuberculosis; Rifampin; Time Factors; Tuberculosis

Topics: Adult; Aged; Aminosalicylic Acids; Cycloserine; Drug Tolerance; Ethionamide; Female; Humans; Isoniazid; Male; Mental Disorders; Middle Aged; Tuberculosis

Topics: Ethionamide; Female; Goiter; Humans; Hypothyroidism; Iodine; Male; Middle Aged; Thyroid Function Tests; Thyroid Hormones; Thyrotropin; Tuberculosis

Topics: Adolescent; Adult; Age Factors; Antitubercular Agents; Berlin; Child; Child, Preschool; Drug Resistance, Microbial; Drug Synergism; Ethambutol; Ethionamide; Humans; Infant; Isoniazid; Middle Aged; Rifampin; Streptomycin; Time Factors; Tuberculin Test; Tuberculosis

Topics: Adrenal Cortex Hormones; Aminosalicylic Acids; Anti-Bacterial Agents; Antitubercular Agents; Ethambutol; Ethionamide; Humans; Isoniazid; Rifampin; Streptomycin; Tuberculosis

Topics: Acids; Animals; Central Nervous System Diseases; Child; Child, Preschool; Cycloserine; Drug Synergism; Ethionamide; Humans; Hydrocortisone; Isoniazid; Pyridoxine; Rats; Tryptophan; Tuberculosis; Vitamin B 6 Deficiency; Xanthurenates

Topics: Administration, Oral; Animals; Drug Combinations; Ethambutol; Ethionamide; Evaluation Studies as Topic; Isoniazid; Mice; Rifampin; Streptomycin; Time Factors; Tuberculosis

Topics: Aminosalicylic Acids; Drug Combinations; Drug Synergism; Ethionamide; Female; Humans; Isoniazid; Male; Middle Aged; Phenylthiourea; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Pulmonary

Topics: Animals; Drug Combinations; Drug Resistance, Microbial; Ethambutol; Ethionamide; Isoniazid; Mice; Mycobacterium Infections; Phenylthiourea; Rifampin; Streptomycin; Time Factors; Tuberculosis

Topics: Africa, Eastern; Bacteriological Techniques; Drug Resistance, Microbial; Ethionamide; Humans; In Vitro Techniques; Isoniazid; Mycobacterium tuberculosis; Species Specificity; Thioacetazone; Tuberculosis

Topics: Animals; Ethambutol; Ethionamide; Guinea Pigs; Isoniazid; Mycobacterium tuberculosis; Rifampin; Streptomycin; Thioacetazone; Tuberculosis

Topics: Adult; Antitubercular Agents; Cycloserine; Ethambutol; Ethionamide; Female; Humans; Isoniazid; Male; Niacinamide; Pyrazinamide; Reflex Sympathetic Dystrophy; Rifampin; Tuberculosis; Vitamin B Deficiency

Topics: Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Drug Synergism; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Oxytetracycline; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Antitubercular Agents; Drug Resistance, Microbial; Ethambutol; Ethionamide; Germany, West; Hospitals, Convalescent; Humans; Isoniazid; Mycobacterium tuberculosis; Rifampin; Streptomycin; Tuberculosis

Topics: Animals; Ethambutol; Ethionamide; Follow-Up Studies; Isoniazid; Lung; Mice; Mycobacterium tuberculosis; Rifampin; Spleen; Streptomycin; Tuberculosis

Topics: Brazil; Cycloserine; Drug Resistance, Microbial; Ethionamide; Humans; Isoniazid; Pyrazinamide; Tuberculosis

Topics: Animals; Antitubercular Agents; Ethionamide; Guinea Pigs; Mice; Rabbits; Tuberculosis

Topics: Antitubercular Agents; Cycloserine; Ethionamide; Humans; Isoniazid; Liver; Pyrazinamide; Tuberculosis

Topics: Africa; Aminosalicylic Acids; Antitubercular Agents; Costs and Cost Analysis; Developing Countries; Drug Resistance, Microbial; Ethionamide; Humans; India; Isoniazid; Pyrazinamide; Streptomycin; Tuberculosis

Topics: Cycloserine; Drug Resistance, Microbial; Drug Synergism; Ethionamide; Humans; Isoniazid; Morocco; Pyrazinamide; Streptomycin; Time Factors; Tuberculosis

Topics: Adolescent; Adult; Aged; Aminosalicylic Acids; Ethionamide; Female; Humans; Isoniazid; Isonicotinic Acids; Male; Middle Aged; Statistics as Topic; Streptomycin; Tuberculosis

Topics: Animals; Antitubercular Agents; Cycloserine; Ethambutol; Ethionamide; Guinea Pigs; In Vitro Techniques; Isoniazid; Mycobacterium tuberculosis; Phenylthiourea; Pyrazinamide; Streptomycin; Thioacetazone; Time Factors; Tuberculosis

Topics: Aminosalicylic Acids; Costs and Cost Analysis; Cycloserine; Drug Synergism; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Pyrazinamide; Streptomycin; Thioacetazone; Tuberculosis; Viomycin

Topics: Animals; Antitubercular Agents; Cycloserine; Ethambutol; Ethionamide; Guinea Pigs; In Vitro Techniques; Isoniazid; Methods; Phenylthiourea; Pyrazinamide; Streptomycin; Thioacetazone; Tuberculosis

Topics: Antitubercular Agents; Cycloserine; Drug Resistance, Microbial; Drug Synergism; Ethambutol; Ethionamide; Humans; Mycobacterium tuberculosis; Phenylthiourea; Pyrazinamide; Rifampin; Thiosemicarbazones; Tuberculosis; Viomycin

Topics: Animals; Bacteriological Techniques; Cell Division; Cortisone; Ethionamide; Female; Isoniazid; Lymphocytes; Macrophages; Mice; Mitosis; Mycobacterium bovis; Phagocytosis; Thymus Gland; Tuberculosis

Topics: Antitubercular Agents; Chronic Disease; Ethionamide; Humans; Methods; Tuberculosis

Topics: Animals; Antitubercular Agents; Drug Synergism; Ethionamide; Guinea Pigs; Tuberculosis

Topics: Ambulatory Care; Ethionamide; Humans; Indicators and Reagents; Tuberculosis

Topics: Aminosalicylic Acids; Antitubercular Agents; Drug Resistance, Microbial; Ethionamide; Humans; Isoniazid; Pyrazinamide; Streptomycin; Tuberculosis

Topics: Cycloserine; Ethionamide; Ferricyanides; Fluorescence; Humans; Indicators and Reagents; Methods; Pyrazinamide; Tuberculosis

Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Ethionamide; Female; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications, Infectious; Tuberculosis

Topics: Animals; Drug Synergism; Ethionamide; Isoniazid; Mice; Models, Theoretical; Streptomycin; Tuberculosis

Topics: Cycloserine; Drug Synergism; Ethionamide; Humans; Pyrazinamide; Tuberculosis

Topics: Adult; Aged; Ethionamide; Female; Humans; Iodine Isotopes; Isoniazid; Male; Middle Aged; Phenobarbital; Reflex Sympathetic Dystrophy; Tuberculosis

Topics: Aminosalicylic Acids; Animals; Antitubercular Agents; Cycloserine; Drug Resistance, Microbial; Ethambutol; Ethionamide; Female; Isoniazid; Kanamycin; Mice; Phenylthiourea; Streptomycin; Tuberculosis; Viomycin

Topics: Drug Resistance, Microbial; Ethionamide; Humans; Mycobacterium tuberculosis; Tuberculosis

Topics: Aminosalicylic Acids; Animals; Antitubercular Agents; Cycloserine; Ethambutol; Ethionamide; Isoniazid; Kanamycin; Male; Mice; Mycobacterium; Pyrazinamide; Streptomycin; Tuberculosis

Topics: Antitubercular Agents; Child; Cycloserine; Ethionamide; Humans; International Cooperation; Mass Chest X-Ray; Pyrazinamide; Research; Skin Tests; Tuberculin Test; Tuberculosis; Tuberculosis, Pulmonary

Topics: Analgesics; Brazil; Ethionamide; Humans; Pyrazinamide; Tuberculosis

Topics: Aminosalicylic Acids; Animals; Antitubercular Agents; Cycloserine; Ethambutol; Ethionamide; Guinea Pigs; Kanamycin; Mice; Phenylthiourea; Pyrazinamide; Rabbits; Tuberculosis; Tuberculosis, Avian

Topics: Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Drug Resistance, Microbial; Ethionamide; Humans; Isoniazid; Kanamycin; Pyrazinamide; Streptomycin; Tuberculosis; Viomycin

Topics: Animals; Ethionamide; Guinea Pigs; Mice; Mycobacterium tuberculosis; Tuberculosis

Topics: Animals; Ethionamide; Humans; In Vitro Techniques; Mice; Tuberculosis

Topics: Cycloserine; Drug Combinations; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Drug Tolerance; Ethionamide; Isoniazid; Kanamycin; Pyrazinamide; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Drug Therapy; Ethionamide; Follow-Up Studies; Pyrazinamide; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Zimbabwe

Topics: Agar; Carbohydrate Metabolism; Culture Media; Ethionamide; Mycobacterium tuberculosis; Oxidation-Reduction; Pharmacology; Rabbits; Research; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Kanamycin; Mycobacterium tuberculosis; Pharmacology; Research; Streptomycin; Tuberculosis; Viomycin

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Ethionamide; Hepatomegaly; Isoniazid; Kanamycin; Liver Function Tests; Pharmacology; Pyrazinamide; Toxicology; Tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Viomycin

Topics: Animals; Ethionamide; Mice; Mycobacterium tuberculosis; Pharmacology; Rabbits; Research; Safrole; Sulfoxides; Toxicology; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Therapy; Ethionamide; Isoniazid; Kidney; Nephrectomy; Statistics as Topic; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Renal

Topics: Child; Drug Therapy; Ethionamide; Humans; Infant; Isoniazid; Tuberculosis

Topics: Child; Drug Therapy; Ethionamide; Humans; Infant; Toxicology; Tuberculosis

Topics: Child; Drug Therapy; Ethionamide; Humans; Infant; Toxicology; Tuberculosis

Topics: Animals; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Kanamycin; Mice; Mycobacterium tuberculosis; Research; Tuberculosis

Topics: Drug Therapy; Ethionamide; Toxicology; Treatment Outcome; Tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary

Topics: Cycloserine; Drug Therapy; Ethionamide; Isoniazid; Pyrazinamide; Radiography, Thoracic; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Cycloserine; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Ethionamide; Kanamycin; Pyrazinamide; Retreatment; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Capreomycin; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Ethambutol; Ethionamide; Kanamycin; Phenylthiourea; Pyrazinamide; Retreatment; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Animals; Ethionamide; Guinea Pigs; Kanamycin; Pyrazinamide; Research; Tuberculosis

Topics: Communicable Diseases; Ethionamide; Female; Humans; Infant; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pyrazinamide; Tuberculosis

Topics: Clinical Protocols; Drug Therapy; Ethionamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Animals; Ethionamide; Humans; In Vitro Techniques; Tuberculosis

Topics: Animals; Ethionamide; Guinea Pigs; In Vitro Techniques; Tuberculosis

Topics: Animals; Ethionamide; Guinea Pigs; Humans; Mice; Tuberculosis

Topics: Ethionamide; Humans; Tuberculosis

Topics: Antitubercular Agents; Culture Media; Drug Resistance, Microbial; Ethionamide; Humans; In Vitro Techniques; Phenylthiourea; Thiosemicarbazones; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Child; Cycloserine; Ethionamide; Isoniazid; Kanamycin; Mycobacterium Infections; Prednisone; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Cardiovascular; Tuberculosis, Meningeal; Tuberculosis, Miliary; Tuberculosis, Osteoarticular; Tuberculosis, Pleural; Tuberculosis, Pulmonary; Tuberculosis, Urogenital; Viomycin

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Antitubercular Agents; Child; Cycloserine; Drug Tolerance; Ethionamide; Isoniazid; Oxytetracycline; Pyrazinamide; Streptomycin; Tetracycline; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pyrazinamide; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Chemical and Drug Induced Liver Injury; Ethionamide; Hepatitis; Jaundice; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Animals; Deficiency Diseases; Ethionamide; Fishes; Humans; Isoniazid; Liver Extracts; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Isoniazid; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Classification; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Epidemiology; Ethionamide; Humans; Kanamycin; Lung Diseases; Microbiology; Mycobacterium; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Diabetes Mellitus; Ethionamide; Isoniazid; Pneumothorax; Pneumothorax, Artificial; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Phenylthiourea; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Ethionamide; Gastroenterology; Isoniazid; Muscle Relaxants, Central; Sorbitol; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adrenocorticotropic Hormone; Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Ethionamide; Isoniazid; Kanamycin; Prednisone; Rest; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Ethionamide; Isoniazid; Kanamycin; Neomycin; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Cycloserine; Depression; Depressive Disorder; Ethionamide; Isoniazid; Pyridoxine; Suicide; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Kanamycin; Pneumonectomy; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Antitubercular Agents; Cycloserine; Ethionamide; Isoniazid; Kanamycin; Nephrectomy; Nephritis; Pyrazinamide; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Renal; Tuberculosis, Urogenital; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Antibiotics, Antitubercular; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Kanamycin; Pyrazinamide; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Anti-Infective Agents; Antitubercular Agents; Bacteriology; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Kanamycin; Phenylthiourea; Pyrazinamide; Statistics as Topic; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Adrenal Cortex Hormones; Aminosalicylic Acid; Aminosalicylic Acids; Child; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethambutol; Ethionamide; Isoniazid; Kanamycin; Mycobacterium Infections; Pharmacology; Prognosis; Pyrazinamide; Streptomycin; Surgical Procedures, Operative; Thiosemicarbazones; Toxicology; Tuberculosis; Tuberculosis, Miliary; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Bacteriological Techniques; Biomedical Research; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Poland; Pyrazinamide; Sputum; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Alanine Transaminase; Alcoholism; Aminosalicylic Acid; Aminosalicylic Acids; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Child; Diabetes Mellitus; Ethionamide; Hepatitis; Hepatitis A; Isoniazid; Jaundice; Liver Cirrhosis; Pyrazinamide; Pyridoxine; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Blood Cell Count; Blood Glucose; Blood Sedimentation; Emaciation; Ethionamide; Fever; Isoniazid; Nitrogen; Oxyphenbutazone; Pleural Effusion; Prothrombin; Radiography, Thoracic; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pleural; Tuberculosis, Pulmonary

Topics: Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Radiography, Thoracic; Sputum; Surgical Procedures, Operative; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Blood Chemical Analysis; Ethionamide; Humans; Lung; Spectrophotometry; Tuberculosis; Tuberculosis, Pulmonary

Topics: Animals; Bacillus; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Mice; Pathology; Research; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Ethionamide; Isoniazid; Toxicology; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Biomedical Research; Cycloserine; Drug Resistance, Microbial; Drug Therapy; Ethionamide; Isoniazid; Japan; Kanamycin; Kanamycin Resistance; Mycobacterium tuberculosis; Sputum; Streptomycin; Tuberculosis

Topics: Adrenal Cortex Hormones; Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Dihydrostreptomycin Sulfate; Ethambutol; Ethionamide; Humans; Isoniazid; Kanamycin; Oxytetracycline; Phenylthiourea; Pyrazinamide; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Renal; Viomycin

Topics: Cycloserine; Ethionamide; Kanamycin; Pyrazinamide; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Drug Eruptions; Dyspepsia; Ethionamide; Feeding and Eating Disorders; Headache; Humans; Nausea; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Vertigo; Vomiting

Topics: Child; Ethionamide; Isoniazid; Lymph Nodes; Toxicology; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Pulmonary

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Child; Drug Therapy; Ethionamide; Humans; Isoniazid; Knee Joint; Pyrazinamide; Radiography; Streptomycin; Surgical Procedures, Operative; Toxicology; Tuberculosis; Tuberculosis, Osteoarticular; Viomycin

Topics: Anxiety; Depression; Ethionamide; Feeding and Eating Disorders; Isoniazid; Mental Disorders; Niacin; Nicotinic Acids; Pellagra; Peripheral Nervous System Diseases; Psychoses, Substance-Induced; Psychotic Disorders; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Vitamin B 6 Deficiency; Vitamin B Complex

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Blood Glucose; Carbohydrate Metabolism; Cycloserine; Diabetes Mellitus; Drug Tolerance; Ethionamide; Humans; Isoniazid; Kanamycin; Pharmacology; Pyrazinamide; Rifamycins; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Pulmonary

Topics: Drug Therapy; Ethionamide; Humans; Infusions, Intravenous; Injections; Injections, Intravenous; Tuberculosis

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Biomedical Research; Clinical Laboratory Techniques; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Ethionamide; Isoniazid; Morocco; Radiography, Thoracic; Sputum; Tuberculin Test; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Biomedical Research; Cycloserine; Drug Therapy; Ethionamide; Isoniazid; Pyridoxine; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Renal

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Biopsy; Chemical and Drug Induced Liver Injury; Cycloserine; Drug Hypersensitivity; Ethionamide; France; Hepatitis; Isoniazid; Japan; Kanamycin; Liver Function Tests; Oxytetracycline; Pathology; Prednisone; Streptomycin; Sulfisoxazole; Toxicology; Tuberculosis

Topics: Alanine Transaminase; Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Ethionamide; Fructose-Bisphosphatase; Hepatitis A; Isoniazid; Liver; Liver Function Tests; Nucleotidases; Oxidoreductases; Pyrazinamide; Sorbitol; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Biomedical Research; Drug Therapy; Ethionamide; Humans; Isoniazid; Streptomycin; Thiosemicarbazones; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Hypersensitivity; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pyrazinamide; Sputum; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Yugoslavia

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Ethambutol; Ethionamide; Geriatrics; Hospitals, State; Isoniazid; Kanamycin; Pyrazinamide; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Biomedical Research; Blood; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Mice; Oxadiazoles; Pharmacology; Pneumothorax; Pneumothorax, Artificial; Pyrazinamide; Radiography, Thoracic; Sputum; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Urine

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Bacillus; Cycloserine; Dihydrostreptomycin Sulfate; Drug Resistance; Drug Resistance, Microbial; Drug Therapy; Ethionamide; Geriatrics; Isoniazid; Kanamycin; Pyrazinamide; Sputum; Streptomycin; Thiosemicarbazones; Toxicology; Tuberculosis; Viomycin

Topics: Adolescent; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus; Diabetes Mellitus, Type 1; Drug Therapy; Ethionamide; Humans; Tuberculosis

Topics: Animals; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Kanamycin; Liver; Mice; Mycobacterium; Mycobacterium tuberculosis; Rats; Research; Tuberculosis; Tuberculosis, Avian

Topics: Drug Therapy; Ethionamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Drug Therapy; Ethionamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adolescent; Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Drug Synergism; Drug Therapy; Ethionamide; Humans; Isoniazid; Kanamycin; Mycobacterium tuberculosis; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Meningeal

Topics: Adrenal Cortex Hormones; Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Classification; Cycloserine; Drug Therapy; Ethionamide; Isoniazid; Kanamycin; Oxytetracycline; Pyrazinamide; Rest; Social Isolation; Streptomycin; Surgical Procedures, Operative; Thiosemicarbazones; Toxicology; Tuberculosis; Viomycin

Topics: Chemical and Drug Induced Liver Injury; Drug Therapy; Ethionamide; Hepatitis A; Liver Function Tests; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Humans; Lung; Metabolism; Pneumonia; Tuberculosis; Tuberculosis, Pulmonary

Topics: Child; Ethionamide; Humans; Tuberculosis; Tuberculosis, Meningeal

Topics: Antitubercular Agents; Cycloserine; Ethionamide; Humans; Pneumonectomy; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Animals; Drug Therapy; Ethionamide; Foundations; Guinea Pigs; Tuberculosis; Tuberculosis, Pulmonary

Topics: Drug Therapy; Ethionamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Perfusion; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anilides; Animals; Antitubercular Agents; Ethionamide; Mice; Phenylthiourea; Tuberculosis

Topics: Antitubercular Agents; Ethionamide; Phenylthiourea; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Ethionamide; Humans; Stomach; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Humans; Treatment Outcome; Tuberculosis; Tuberculosis, Pulmonary

Topics: Bacillus; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Ethionamide; Humans; Kanamycin; Phenylthiourea; Tuberculosis

Topics: Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Thioacetazone; Thiosemicarbazones; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Hong Kong; Humans; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Geriatrics; Isoniazid; Jaundice; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Drug Hypersensitivity; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pyrazinamide; Streptomycin; Tuberculosis; Viomycin

Topics: Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Tuberculosis; Tuberculosis, Pulmonary

Topics: Diabetes Mellitus; Ethionamide; Hypoglycemia; Hypoglycemic Agents; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Poland; Radiography, Thoracic; Retreatment; Statistics as Topic; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Ethionamide; Humans; Isoniazid; Kanamycin; Oxytetracycline; Pyrazinamide; Streptomycin; Thioacetazone; Thiosemicarbazones; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Ethionamide; Isoniazid; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Humans; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adolescent; Ethionamide; Humans; Psychology, Adolescent; Tuberculosis; Tuberculosis, Pulmonary

Topics: Amyloidosis; Antitubercular Agents; Cycloserine; Deafness; Drug Hypersensitivity; Duodenal Ulcer; Ethionamide; Isoniazid; Kidney Diseases; Liver Diseases; Neuritis; Psychotic Disorders; Pyrazinamide; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Vertigo; Viomycin

Topics: Antitubercular Agents; Cycloserine; Ethionamide; Kanamycin; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Ethionamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Ethionamide; Humans; Isoniazid; Sputum; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Ethionamide; Isoniazid; Kanamycin; Streptomycin; Sulfonamides; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Antitubercular Agents; Cycloserine; Diagnosis, Differential; Ethionamide; Isoniazid; Kanamycin; Lung Neoplasms; Neoplasms; Pneumonectomy; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Czechoslovakia; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pyrazinamide; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Ethionamide; Humans; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminoacylation; Aminosalicylic Acid; Aminosalicylic Acids; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Mycobacterium tuberculosis; Proteins; Research; Streptomycin; Tuberculosis

Topics: Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Pyrazinamide; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Anaphylaxis; Anti-Bacterial Agents; Caffeine; Drug Eruptions; Drug Hypersensitivity; Ethionamide; Histamine H1 Antagonists; Hydrocortisone; Isoniazid; Norepinephrine; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Chlortetracycline; Cycloserine; Ethionamide; Humans; Kanamycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adolescent; Child; Ethionamide; Humans; Infant; Tuberculosis

Topics: Administration, Intravenous; Ethionamide; Humans; Recurrence; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adolescent; Adrenal Cortex Hormones; Aminosalicylic Acid; Aminosalicylic Acids; Anti-Bacterial Agents; Blindness; Chemical and Drug Induced Liver Injury; Cycloserine; Drug Eruptions; Ethionamide; Hepatitis; Isoniazid; Optic Neuritis; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Anti-Infective Agents; Antitubercular Agents; Collapse Therapy; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pneumonectomy; Pyrazinamide; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Ethionamide; Geriatrics; Isoniazid; Japan; Kanamycin; Pathology; Statistics as Topic; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Streptomycin; Toxicology; Tuberculosis; Tuberculosis, Pulmonary

Topics: Drug Therapy; Ethionamide; Humans; Tuberculosis; Tuberculosis, Pulmonary

Topics: Ethionamide; Isoniazid; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Bacillus; Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Isoniazid; Pyrazinamide; Streptomycin; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Cycloserine; Dihydrostreptomycin Sulfate; Ethionamide; Iproniazid; Isoniazid; Kanamycin; Oxytetracycline; Pyrazinamide; Streptomycin; Thiosemicarbazones; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Aminosalicylic Acid; Aminosalicylic Acids; Bacillus; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Isoniazid; Streptomycin; Tuberculosis

Topics: Ethionamide; Humans; Isoniazid; Tuberculosis; Tuberculosis, Meningeal; Veins

Topics: Administration, Intravenous; Ethionamide; Humans; Isoniazid; Tuberculosis; Tuberculosis, Meningeal

Topics: Cycloserine; Ethionamide; Humans; Tuberculosis; Tuberculosis, Pulmonary

Topics: Cycloserine; Ethionamide; Humans; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Cycloserine; Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Drug Resistance; Drug Resistance, Microbial; Ethionamide; Humans; Tuberculosis; Tuberculosis, Pulmonary

Topics: Cycloserine; Ethionamide; Isoniazid; Kanamycin; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary; Viomycin

Topics: Ethionamide; Humans; Tuberculosis; Tuberculosis, Pulmonary

Topics: Child; Ethionamide; Humans; Tuberculosis

Topics: Antitubercular Agents; Ethionamide; Humans; Tuberculosis; Tuberculosis, Meningeal

Topics: Anti-Bacterial Agents; Antitubercular Agents; Cycloserine; Ethionamide; Humans; Oxytetracycline; Protein Synthesis Inhibitors; Tetracycline; Tuberculosis; Tuberculosis, Pulmonary

Topics: Anti-Bacterial Agents; Antitubercular Agents; Avitaminosis; Ethionamide; Isoniazid; Niacin; Nicotinic Acids; Pellagra; Tuberculosis

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bacillus; Dermatologic Agents; Ethionamide; Insecta; Tuberculosis

Topics: Animals; Antitubercular Agents; Ethionamide; Isoniazid; Mice; Tuberculosis

Topics: Antitubercular Agents; Cyclopropanes; Cycloserine; Ethionamide; Humans; Pyrazinamide; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Cycloserine; Ethionamide; Humans; Isoniazid; Pneumonectomy; Pulmonary Surgical Procedures; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Child; Ethionamide; Humans; Infant; Tuberculosis

Topics: Antitubercular Agents; Disease Susceptibility; Ethionamide; In Vitro Techniques; Mycobacteriaceae; Mycobacterium tuberculosis; Tuberculosis

Topics: Antitubercular Agents; Ethionamide; Niacin; Nicotinic Acids; Tuberculosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Black People; Ethionamide; Humans; Lung; Pilot Projects; Streptomycin; Tuberculosis; Tuberculosis, Pulmonary; Uganda

Topics: Antitubercular Agents; Ethionamide; Tuberculosis

Topics: Antitubercular Agents; Child; Ethionamide; Infant; Tuberculosis