Antitubercular Agents: Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.Mycobacterium tuberculosis: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Thioacetazone: A thiosemicarbazone that is used in association with other antimycobacterial agents in the initial and continuation phases of antituberculosis regimens. Thiacetazone containing regimens are less effective than the short-course regimen recommended by the International Union Against Tuberculosis and are used in some developing countries to reduce drug costs. (From Martindale, The Extra Pharmacopoeia, 30th ed, p217)Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.Antibiotics, Antitubercular: Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Ethambutol: An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863)Tuberculosis, Ocular: Tuberculous infection of the eye, primarily the iris, ciliary body, and choroid.Tuberculosis: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.Pyrazinamide: A pyrazine that is used therapeutically as an antitubercular agent.NitroimidazolesEthylenediaminesNigella: A plant genus of the family RANUNCULACEAE.Cryoanesthesia: ANESTHESIA achieved by lowering either BODY TEMPERATURE (core cooling) or SKIN TEMPERATURE (external cooling).Ethionamide: A second-line antitubercular agent that inhibits mycolic acid synthesis.Adamantane: A tricyclo bridged hydrocarbon.Tuberculosis, Osteoarticular: Tuberculosis of the bones or joints.Mycolic AcidsTuberculosis, Gastrointestinal: TUBERCULOSIS that involves any region of the GASTROINTESTINAL TRACT, mostly in the distal ILEUM and the CECUM. In most cases, MYCOBACTERIUM TUBERCULOSIS is the pathogen. Clinical features include ABDOMINAL PAIN; FEVER; and palpable mass in the ileocecal area.Phenothiazines: Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.Tuberculosis, Male Genital: MYCOBACTERIUM infections of the male reproductive tract (GENITALIA, MALE).Tuberculoma, Intracranial: A well-circumscribed mass composed of tuberculous granulation tissue that may occur in the cerebral hemispheres, cerebellum, brain stem, or perimeningeal spaces. Multiple lesions are quite common. Management of intracranial manifestations vary with lesion site. Intracranial tuberculomas may be associated with SEIZURES, focal neurologic deficits, and INTRACRANIAL HYPERTENSION. Spinal cord tuberculomas may be associated with localized or radicular pain, weakness, sensory loss, and incontinence. Tuberculomas may arise as OPPORTUNISTIC INFECTIONS, but also occur in immunocompetent individuals.Tuberculosis, Cutaneous: Tuberculosis of the skin. It includes scrofuloderma and tuberculid, but not LUPUS VULGARIS.Tuberculosis, Multidrug-Resistant: Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.Tuberculosis, Pulmonary: MYCOBACTERIUM infections of the lung.Drug Dosage Calculations: Math calculations done for preparing appropriate doses of medicines, taking into account conversions of WEIGHTS AND MEASURES. Mistakes are one of the sources of MEDICATION ERRORS.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Drug Discovery: The process of finding chemicals for potential therapeutic use.South Africa: A republic in southern Africa, the southernmost part of Africa. It has three capitals: Pretoria (administrative), Cape Town (legislative), and Bloemfontein (judicial). Officially the Republic of South Africa since 1960, it was called the Union of South Africa 1910-1960.Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.Streptomycin: An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.Antiperspirants: Agents that are put on the SKIN to reduce SWEATING or prevent excess sweating (HYPERHIDROSIS).Methylmethacrylate: The methyl ester of methacrylic acid. It polymerizes easily to form POLYMETHYL METHACRYLATE. It is used as a bone cement.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Eye Diseases: Diseases affecting the eye.Bacteriology: The study of the structure, growth, function, genetics, and reproduction of bacteria, and BACTERIAL INFECTIONS.Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases.Nobel PrizeHistory, 19th Century: Time period from 1801 through 1900 of the common era.Book SelectionHydrazinesTuberculosis, Female Genital: MYCOBACTERIUM infections of the female reproductive tract (GENITALIA, FEMALE).Mucorales: An order of zygomycetous fungi, usually saprophytic, causing damage to food in storage, but which may cause respiratory infection or MUCORMYCOSIS in persons suffering from other debilitating diseases.Hydrazones: Compounds of the general formula R:N.NR2, as resulting from the action of hydrazines with aldehydes or ketones. (Grant & Hackh's Chemical Dictionary, 5th ed)Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.Lopinavir: An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.Partnership Practice, Dental: A voluntary contract between two or more dentists who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses.Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.PyrimidinonesBulimia: Eating an excess amount of food in a short period of time, as seen in the disorder of BULIMIA NERVOSA. It is caused by an abnormal craving for food, or insatiable hunger also known as "ox hunger".

Epidemiology of drug-resistant tuberculosis in Texas. (1/3795)

During 1987-1996, over 22,000 tuberculosis cases were reported in Texas, at an average annual incidence rate of 12.5 cases per 100,000 population. Counties with the highest rates were located along the Mexico-Texas border and in northwestern Texas. Nine percent of cases were resistant to at least one of the five first-line antituberculosis drugs used for treatment. Almost 5 percent (4.6%) were resistant to isoniazid, either alone or in combination with other antibiotics; 2.3% were resistant to rifampin; and only 1.3% were resistant to both isoniazid and rifampin. Being a recurrent case, being foreign-born, being 20-39 years of age, and residing in a Mexico-Texas border county were independent risk factors for isoniazid resistance and rifampin resistance. Tuberculosis patients with human immunodeficiency virus (HIV) infection were more likely to have rifampin resistance and less likely to have isoniazid resistance than patients without HIV infection. Factors associated with multi-drug-resistant tuberculosis included a history of previous tuberculosis (relative risk (RR) = 4.91, 95% confidence interval (CI) 3.5-6.8), non-US birth (RR = 2.69, 95% CI 2.1-3.5), age younger than 20 years (RR = 1.97, 95% CI 1.1-3.5), age 20-39 years (RR = 1.82, 95% CI 1.3-2.6), and residence in a Mexico-Texas border county (RR = 2.33, 95% CI 1.8-3.1).  (+info)

Issues in the treatment of active tuberculosis in human immunodeficiency virus-infected patients. (2/3795)

Most HIV-infected patients with tuberculosis can be treated satisfactorily with standard regimens with expectations of good results. Treatment of tuberculosis in these patients has been complicated by the introduction of HAART, which relies on drugs that interfere with the most potent class of antituberculous medications. Rifampin-free regimens or regimens that employ rifabutin may be acceptable strategies for patients who are receiving protease inhibitors, although these regimens have not been rigorously evaluated in patients with AIDS. At present, there is good reason to believe that a 6-month course of a rifabutin-containing regimen or a 9-12-month course of a regimen of streptomycin, isoniazid, and pyrazinamide should be adequate therapy for most patients with drug-susceptible disease. As the treatment of HIV infection with antiretroviral agents evolves, the treatment of tuberculosis in patients with AIDS is likely to evolve as well. This will require careful coordination of antituberculosis and antiretroviral therapies.  (+info)

Reduced pyrazinamidase activity and the natural resistance of Mycobacterium kansasii to the antituberculosis drug pyrazinamide. (3/3795)

Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug that requires conversion to the bactericidal compound pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) activity of nicotinamidase to show activity against Mycobacterium tuberculosis. Mutations leading to a loss of PZase activity cause PZA resistance in M. tuberculosis. M. kansasii is naturally resistant to PZA and has reduced PZase activity along with an apparently detectable nicotinamidase activity. The role of the reduction in PZase activity in the natural PZA resistance of M. kansasii is unknown. The MICs of PZA and POA for M. kansasii were determined to be 500 and 125 micrograms/ml, respectively. Using [14C]PZA and [14C]nicotinamide, we found that M. kansasii had about 5-fold-less PZase activity and about 25-fold-less nicotinamidase activity than M. tuberculosis. The M. kansasii pncA gene was cloned on a 1.8-kb BamHI DNA fragment, using M. avium pncA probe. Sequence analysis showed that the M. kansasii pncA gene encoded a protein with homology to its counterparts from M. tuberculosis (69.9%), M. avium (65.6%), and Escherichia coli (28.5%). Transformation of naturally PZA-resistant M. bovis BCG with M. kansasii pncA conferred partial PZA susceptibility. Transformation of M. kansasii with M. avium pncA caused functional expression of PZase and high-level susceptibility to PZA, indicating that the natural PZA resistance in M. kansasii results from a reduced PZase activity. Like M. tuberculosis, M. kansasii accumulated POA in the cells at an acidic pH; however, due to its highly active POA efflux pump, the naturally PZA-resistant species M. smegmatis did not. These findings suggest the existence of a weak POA efflux mechanism in M. kansasii.  (+info)

Pharmacokinetics of ethambutol under fasting conditions, with food, and with antacids. (4/3795)

Ethambutol (EMB) is the most frequent "fourth drug" used for the empiric treatment of Mycobacterium tuberculosis and a frequently used drug for infections caused by Mycobacterium avium complex. The pharmacokinetics of EMB in serum were studied with 14 healthy males and females in a randomized, four-period crossover study. Subjects ingested single doses of EMB of 25 mg/kg of body weight under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. Serum was collected for 48 h and assayed by gas chromatography-mass spectrometry. Data were analyzed by noncompartmental methods and by a two-compartment pharmacokinetic model with zero-order absorption and first-order elimination. Both fasting conditions produced similar results: a mean (+/- standard deviation) EMB maximum concentration of drug in serum (Cmax) of 4.5 +/- 1.0 micrograms/ml, time to maximum concentration of drug in serum (Tmax) of 2.5 +/- 0.9 h, and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) of 28.9 +/- 4.7 micrograms.h/ml. In the presence of antacids, subjects had a mean Cmax of 3.3 +/- 0.5 micrograms/ml, Tmax of 2.9 +/- 1.2 h, and AUC0-infinity of 27.5 +/- 5.9 micrograms.h/ml. In the presence of the Food and Drug Administration high-fat meal, subjects had a mean Cmax of 3.8 +/- 0.8 micrograms/ml, Tmax of 3.2 +/- 1.3 h, and AUC0-infinity of 29.6 +/- 4.7 micrograms.h/ml. These reductions in Cmax, delays in Tmax, and modest reductions in AUC0-infinity can be avoided by giving EMB on an empty stomach whenever possible.  (+info)

Use of site-directed mutagenesis to probe the structure, function and isoniazid activation of the catalase/peroxidase, KatG, from Mycobacterium tuberculosis. (5/3795)

A series of mutants bearing single amino acid substitutions often encountered in the catalase/peroxidase, KatG, from isoniazid-resistant isolates of Mycobacterium tuberculosis has been produced by site-directed mutagenesis. The resultant enzymes were overexpressed, purified and characterized. Replacing Cys-20 by Ser abolished disulphide-bridge formation, but did not affect either dimerization of the enzyme or catalysis. The substitution of Thr-275, which is probably involved in electron transfer from the haem, by proline resulted in a highly unstable enzyme with insignificant enzyme activities. The most commonly occurring substitution in drug-resistant clinical isolates is the replacement of Ser-315 by Thr; this lowered catalase and peroxidase activities by 50% and caused a significant decrease in the KatG-mediated inhibition of the activity of the NADH-dependent enoyl-[acyl-carrier protein] reductase, InhA, in vitro. The ability of this enzyme to produce free radicals from isoniazid was severely impaired, as judged by its loss of NitroBlue Tetrazolium reduction activity. Replacement of Leu-587 by Pro resulted in marked instability of KatG, indicating that the C-terminal domain is also important for structural and functional integrity.  (+info)

Susceptibility of multidrug-resistant strains of Mycobacterium tuberculosis to amoxycillin in combination with clavulanic acid and ethambutol. (6/3795)

Thirty clinical isolates of Mycobacterium tuberculosis, 20 of which were multidrug-resistant (MDR), were tested for susceptibility to different combinations of amoxycillin, clavulanic acid and subinhibitory concentrations of ethambutol. beta-Lactamase production was assessed semiquantitatively with the nitrocefin method and susceptibility testing was performed with the BACTEC method. All isolates were beta-lactamase positive and were resistant to 16 mg/L amoxycillin. The MIC of amoxycillin in combination with clavulanic acid was > or =2 mg/L for 27/30 (90%) isolates. Addition of subinhibitory concentrations of ethambutol significantly reduced the MIC of amoxycillin for all tested isolates. Twenty-nine (97%) isolates had an MIC of amoxycillin of < or =0.5 mg/L when subinhibitory concentrations of ethambutol were added; this is well below the concentrations achievable in serum and tissue.  (+info)

Molecular evidence for heterogeneity of the multiple-drug-resistant Mycobacterium tuberculosis population in Scotland (1990 to 1997). (7/3795)

Multiple-drug-resistant Mycobacterium tuberculosis (MDR-MTB) has been well studied in hospitals or health care institutions and in human immunodeficiency virus-infected populations. However, the characteristics of MDR-MTB in the community have not been well investigated. An understanding of its prevalence and circulation within the community will help to estimate the problem and optimize the strategies for control and prevention of its development and transmission. In this study, MDR-MTB isolates from Scotland collected between 1990 and 1997 were characterized, along with non-drug-resistant isolates. The results showed that they were genetically diverse, suggesting they were unrelated to each other and had probably evolved independently. Several new alleles of rpoB, katG, and ahpC were identified: rpoB codon 525 (ACC-->AAC; Thr525Asn); katG codon 128 (CGG-->CAG; Arg128Gln) and codon 291 (GCT-->CCT; Ala291Pro); and the ahpC synonymous substitution at codon 6 (ATT-->ATC). One of the MDR-MTB isolates from an Asian patient had an IS6110 restriction fragment length polymorphism pattern very similar to that of the MDR-MTB W strain and had the same drug resistance-related alleles but did not have any epidemiological connection with the W strains. Additionally, a cluster of M. tuberculosis isolates was identified in our collection of 715 clinical isolates; the isolates in this cluster had genetic backgrounds very similar to those of the W strains, one of which had already developed multiple drug resistances. The diverse population of MDR-MTB in Scotland, along with a low incidence of drug-resistant M. tuberculosis, has implications for the control of the organism and prevention of its spread.  (+info)

Rapid film-based determination of antibiotic susceptibilities of Mycobacterium tuberculosis strains by using a luciferase reporter phage and the Bronx Box. (8/3795)

Detecting antibiotic resistance in Mycobacterium tuberculosis is becoming increasingly important with the global recognition of drug-resistant strains and their adverse impact on clinical outcomes. Current methods of susceptibility testing are either time-consuming or costly; rapid, reliable, simple, and inexpensive methods would be highly desirable, especially in the developing world where most tuberculosis is found. The luciferase reporter phage is a unique reagent well-suited for this purpose: upon infection with viable mycobacteria, it produces quantifiable light which is not observed in mycobacterial cells treated with active antimicrobials. In this report, we describe a modification of our original assay, which allows detection of the emitted light with a Polaroid film box designated the Bronx Box. The technique has been applied to 25 M. tuberculosis reference and clinical strains, and criteria are presented which allow rapid and simple discrimination among strains susceptible or resistant to isoniazid and rifampin, the major antituberculosis agents.  (+info)

  • Anti-Infective Agents publishes original research articles, full-length/mini reviews, drug clinical trial studies and guest edited issues on all the latest and outstanding developments on the medicinal chemistry, biology, pharmacology and use of anti-infective and anti-parasitic agents. (
  • An antitubercular agent often administered in association with isoniazid. (
  • 2 The standard antitubercular treatment regimen, termed DOTS (Directly Observed Therapy, Short-course), is based on the co-administration of age-old drugs like isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) for the first two months, followed by a prolonged treatment with INH and RMP for additional 4-7 months with no guarantee of complete sterilization from the infection. (
  • The project aimed at the development of very robust, predictive and well-validated quantitative structure-activity relationships (QSARs) that assisted us in the design of a series of new potentially active antitubercular compounds from particular relevant core structures, namely, isoniazid, thiobenzanilide, benzimidazole and indole scaffolds. (
  • In spite of a few new antitubercular candidates in phase II and III of the clinical global TB drug pipeline, isoniazid (INH), first synthesized in 1952, is still the treatment of choice for TB and is part of all WHO multidrug recommended regimens. (
  • Antitubercular Agents" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • This paper highlights recent approaches regarding the design of new anti-TB agents, particularly, the enoyl-ACP reductase inhibitors. (
  • Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs. (
  • Moreover, the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mtb all over the world, together with significant levels of co-infection with HIV, makes the search for new antitubercular drugs a major public health challenge. (
  • It has been confirmed that there is an increase in hydrophobicity of the [ at the C-4 position of the phenyl ring, which is attached to the azetidinone nucleus, which results in an increase in the antitubercular potency. (
  • For the treatment of HIV-1 infection in combination with other antiretroviral agents. (
  • Infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to the infectious agents and the toxins they produce. (
  • Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 μg/mL) comparable to triclosan. (
  • These reasons make a compelling case for an urgent need for new and effective antitubercular agents with improved properties such as enhanced activity against MDR strains, reduced toxicity, rapid mycobactericidal mechanism of action and the ability to penetrate host cells and exert antimycobacterial effects in the intracellular environment. (
  • The various study tools used were the patient profile form which recorded all the information, such as name, age, sex, socioeconomic status, life style factors and dietary factors and any concurrent diseases and medications other than antitubercular agents that the patients might be taking. (
  • They had expertise in the use of biological agents for the treatment of rheumatic diseases. (
  • WHO HQ Library catalog › Results of search for 'su:{Antitubercular agents. (
  • This graph shows the total number of publications written about "Antitubercular Agents" by people in this website by year, and whether "Antitubercular Agents" was a major or minor topic of these publications. (
  • DNA-Minor Groove Binding Agents as Anti-Tubercular Probes. (
  • TB47 is highly potent against M. ulcerans and possesses desirable pharmacological attributes and low toxicity that warrant further assessment of this agent for treatment of BU. (
  • These barriers reinforcing the need for development of new antimicrobial agents, that ideally should reduce the time of treatment and be active against susceptible and resistant strains. (
  • Its mechanism of action is unknown and agents with this pharmacophore have not been evaluated against non-tuberculous mycobacteria. (
  • As in previous years, the consensus group to consider the use of biological agents was constituted by rheumatologists from the universities of Erlangen, Leiden, and Vienna in Europe in cooperation with other universities in the USA, Canada, and Europe. (