Antituberculosis (original) (raw)
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Antituberculosis Drug Research: A Critical Overview
Medicinal Research Reviews, 2013
The increasing drug resistance of Mycobacterium tuberculosis to the currently used drugs and HIV coinfection has caused alarm in the international scientific community. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. The objective of this review article is to critically analyze the antitubercular potential of various classes of compounds (quinoline, diamine, quinolone, fluoroquinolone, quinone, nitroimidazole, terpenoid, isonicotinyl, oxazolidinone, pyrimidine, and purine), their possibility to be a future drug candidate, and latest information on the clinical status of some novel antitubercular compounds. Compounds such as moxifloxacin, PA824, and TMC207 are well tolerated and there is no adverse effect shown by them. Moxifloxacin and gatifloxacin shows cross-resistance to the currently used drugs while no cross-resistance observed in case of TMC207 and PA824. Some compounds like OPC67683 and PA824 are bactericidal in nature.
PHARMACOTHERAPEUTIC EVOLUTION OF ANTITUBERCULOSIS DRUG-A REVIEW
Tuberculosis is a cosmopolitan human lung infection caused by Mycobacterium tuberculosis. It represents one of the main causes of death worldwide. The therapeutic management of this disease by antituberculosis drugs faces several obstacles such as low adherence, the long duration of treatment, adverse effects of the drugs and the existance of the latent tuberculosis caused by dormant bacilli. Furthermore, the drug treatment of co-infection HIV and tuberculosis resistant is in a situation of therapeutic deadlock. Therefore, it seemed worthwhile to make an inventory of antituberculosis drugs and have a better understanding of future therapeutic options. This study highlighted the existance of many "doubtful" non-drug treatments proposed to treat tuberculosis before the discovery of modern tuberculosis chemotherapy. Some of them suggested prayers, incantations (heal power of kings), or a simple rest combined with a balanced diet. Others less gentle methods such as the injection of air into the lungs recommended surgical treatments like thoracoplasty. Various treatment based on gold salts, cod liver oil or the sanatorium cures were also tested. The discovery of streptomycin in the 1940, was the beginning of the current anti-tuberculosis therapy. Indeed, research aimed at finding an alternative treatment, to overcome the Streptomycin resistance, led to the introduction in therapy of many other antituberculosis like Para-aminosalicylic acid (1944), Isoniazid (1952), the ethambutol (1957), Rifampicin (1967), the pyrazinamide (1980) and fluoroquinolones (1982). Moreover, in order to shorten the duration of treatment and to limit the the emergence and spread of resistance, combination of antituberculous drugs has been proposed and the treatment of tuberculosis has evolved from monotherapy to quadruple today. In addition, to deal with the appearance of poly-resistant strains and overcome the drawbacks existing tuberculosis drugs, research is underway to identify new biological targets and to develop antituberculosis of the future.
Twenty Years of Global Surveillance of Antituberculosis-Drug Resistance
New England Journal of Medicine, 2016
The NEJM Image Challenge app brings a popular online feature to the smartphone. Optimized for viewing on the iPhone and iPod Touch, the Image Challenge app lets you test your diagnostic skills anytime, anywhere. The Image Challenge app randomly selects from 300 challenging clinical photos published in NEJM, with a new image added each week. View an image, choose your answer, get immediate feedback, and see how others answered. The Image Challenge app is available at the iTunes App Store.
New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects
The Lancet Infectious Diseases, 2014
About 1·3 million people died of tuberculosis in 2012, despite availability of eff ective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in poor patient adherence and loss of patients to follow-up), complex regimens that involve expensive and toxic drugs, toxic eff ects when given with antiretroviral therapy, and multidrug resistance. After 50 years of no antituberculosis drug development, a promising pipeline is emerging through the repurposing of old drugs, re-engineering of existing antibacterial compounds, and discovery of new compounds. A range of novel antituberculosis drugs are in preclinical development, several phase 2 and 3 trials are underway, and use of adjunct therapies is being explored for drug-sensitive and drug-resistant tuberculosis.
Pharmaceuticals
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a curable airborne disease currently treated using a drug regimen consisting of four drugs. Global TB control has been a persistent challenge for many decades due to the emergence of drug-resistant Mtb strains. The duration and complexity of TB treatment are the main issues leading to treatment failures. Other challenges faced by currently deployed TB regimens include drug-drug interactions, miss-matched pharmacokinetics parameters of drugs in a regimen, and lack of activity against slow replicating sub-population. These challenges underpin the continuous search for novel TB drugs and treatment regimens. This review summarizes new TB drugs/drug candidates under development with emphasis on their chemical classes, biological targets, mode of resistance generation, and pharmacokinetic properties. As effective TB treatment requires a combination of drugs, the issue of drug-drug interaction is, therefore, of great concern...
Global Trends In Resistance to Antituberculosis Drugs
The New England …, 2001
Background Data on global trends in resistance to antituberculosis drugs are lacking. Methods We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance.
Antituberculosis activity of clarithromycin
Antimicrobial Agents and Chemotherapy, 1995
Antituberculosis activity of clarithromycin (CLA), a macrolide antibiotic, was investigated in vitro, in macrophages, and in C57BL/6 mice, CLA showed high in vitro MICs (4 to > 16 micrograms/ml) for several strains of Mycobacterium tuberculosis and caused slight enhancement of activity of rifampin (RIF) against H37Rv but failed to increase the activity of either RIF or isoniazid (INH) against other strains. However, inside J774A.1 macrophages, CLA showed high activity and was synergistic with RIF against some strains of tubercle bacilli susceptible or resistant to INH and RIF. In the in vivo studies with a drug-susceptible strain (H37Rv), CLA protected mice from mortality due to tuberculosis for up to 8 weeks of observation. The CFU data for lungs and spleens revealed that the antituberculosis activity of CLA is inferior to those of INH and streptomycin. However, the activity of CLA when used alone or in combination was comparable to that of thiacetazone, indicating its potential...
Analysis of the clinical antibacterial and antituberculosis pipeline
Lancet Infectious Diseases, 2019
This analysis of the global clinical antibacterial pipeline was performed in support of the Global Action Plan on Antimicrobial Resistance. The study analysed to what extent antibacterial and antimycobacterial drugs for systemic human use as well as oral nonsystemic antibacterial drugs for Clostridium difficile infections were active against pathogens included in the WHO priority pathogen list and their innovativeness measured by their absence of cross resistance (new class, target, mode of action). As of 1 July 2018, 30 new chemical entity (NCE) antibacterial drugs, ten biologics, ten NCEs against Mycobacterium tuberculosis, and four NCEs against C. difficile were identified. Of the 30 NCEs, 11 are expected to have some activity against at least one critical priority pathogen expressing carbapenem resistance. The clinical pipeline is dominated by derivatives of established classes and most development candidates display limited innovation. New antibacterial drugs without pre-existing cross resistance are underrepresented and are urgently needed, especially for geographic regions with high resistance rates among Gram-negative bacteria and M. tuberculosis.
An Overview of Antituberculosis Drugs and an Emphasis on Phytotherapeutic Intervention
International Journal for Research in Applied Science and Engineering Technology, 2019
The long duration tuberculosis therapy makes causes several serious side effects, hepatotoxicity being the main. Hepatotoxicity is the most serious adverse effect related to tuberculosis treatment which interrupts the successful completion of tuberculosis treatment antioxidant system of the body effectively neutralises reactive oxygen species formed during the normal metabolic process. Any imbalance in this neutralization process causes oxidative stress leading to causation of various diseases. Research has enabledthe use of several medicinal plants from time to time to treat toxic manifestations from various toxigenic substances. This review is aimed to provide an insight for the phytotherapeutic intervention of the medicinal plants for the effectiveness of the existing tuberculosis therapy
Current Pharmaceutical Design of Antituberculosis Drugs: Future Perspectives
Current Pharmaceutical Design, 2010
The increasing resistance of Mycobacterium tuberculosis to the existing drugs has alarmed the worldwide scientific community. In an attempt to overcome this problem computer-aided drug design has provide an extraordinary support to the different strategies in drug discovery. There are around 250 biological receptors such as enzymes that can be used in principle, for the design of antituberculosis compounds that act by a specific mechanism of action. Also, there more than 5000 compound available in the literature, and that constitute important information in order to search new molecular patterns for the design of new antituberculosis agents. The purpose of this paper is to explored the current state of drug discovery of antituberculosis agents and how the different strategies supported by computeraided drug design methods has influenced in a determinant way in the design of new molecular entities that can result the future antituberculosis drugs.