Abstract:Despite the development of effective treatments, tuberculosis (TB) remains a major health problem. TB continues to infect new victims and kills nearly 2 million people annually. The problem is much greater in resource-limited countries but is present worldwide. Inadequate public health resources, cost, the obligatory long treatment period, and adverse drug effects contribute to treatment failures and relapses. Drug-resistant Mycobacterium tuberculosis (MTB) strains arise spontaneously and are propagated by ina… Show more
“…Some of these newer compounds include oxazolidinones, nitroimidazopyrans, diarylquinolones, pyrrols, ethenylenediamines, ethylenediamides, and benzothiaziones. [88][89][90]. Linezolid, a broad spectrum antibiotic that inhibits protein synthesis by interfering with mRNA binding to the ribosome is currently in phase II trials for the treatment of MDR-TB [87,88].…”
Section: Drug-susceptible Tb [71]mentioning
confidence: 99%
“…[88][89][90]. Linezolid, a broad spectrum antibiotic that inhibits protein synthesis by interfering with mRNA binding to the ribosome is currently in phase II trials for the treatment of MDR-TB [87,88]. Although no large clinical trials have been conducted to date, several small studies indicated that treatment regimens that include Linezolid can be used to successfully treat infections due to MDR-TB [88].…”
Section: Drug-susceptible Tb [71]mentioning
confidence: 99%
“…Sutezolid (PNU100480) and AZD5847 are other, newer oxazolidinones that are also in phase II studies [87]. Some preliminary evidence suggests that these drugs may have a better bioavailability and may be better tolerated by patients [88]. In addition, the two fluoroquinolones moxifloxacin and gatifloxacin are currently in phase III clinical trials [87].…”
Section: Drug-susceptible Tb [71]mentioning
confidence: 99%
“…Limited but promising data are available for diarylquinolones. These drugs reduce adenosine triphosphate (ATP) levels by selectively inhibiting the mycobacterial ATP synthase [87][88][89]. However, they do have little to no effect on other bacteria or eukaryotes.…”
The history of tuberculosis (TB) is intricately connected to the history of humanity. The disease is considered one of the oldest infectious diseases afflicting mankind. Its history is that of colorful, often vibrant descriptions and interpretations, in the attempt of human societies to demystify the origins, causality, and course of this grave and lethal disease, and in the ultimate pursuit of finding a cure. The discovery of the tubercle bacillus on March 24 th 1882, by Robert Koch, led to an unprecedented increase in international research efforts, ultimately resulting in the development of a vaccine and many potent antimicrobial agents and treatment regimens. However, the course of history is often not without some irony, commonly perceived as being unpredictable by those who find themselves immersed in history's path. In this sense, and despite the advances that were made in diagnostics and treatment during the past 70 years, TB continues to challenge mankind on numerous levels even today. The most recent emergence of multidrug-resistant and extensively-drug-resistant strains of Mycobacterium tuberculosis is only a small but significant reflection of the ongoing challenges in the attempt of eradicating this disease. Here we provide a review of the historic aspects of TB leading to a discussion of the current state of the approach to antituberculous treatment, including the aspects of microbiology, diagnostics, antimicrobial therapy, and public health.
“…Some of these newer compounds include oxazolidinones, nitroimidazopyrans, diarylquinolones, pyrrols, ethenylenediamines, ethylenediamides, and benzothiaziones. [88][89][90]. Linezolid, a broad spectrum antibiotic that inhibits protein synthesis by interfering with mRNA binding to the ribosome is currently in phase II trials for the treatment of MDR-TB [87,88].…”
Section: Drug-susceptible Tb [71]mentioning
confidence: 99%
“…[88][89][90]. Linezolid, a broad spectrum antibiotic that inhibits protein synthesis by interfering with mRNA binding to the ribosome is currently in phase II trials for the treatment of MDR-TB [87,88]. Although no large clinical trials have been conducted to date, several small studies indicated that treatment regimens that include Linezolid can be used to successfully treat infections due to MDR-TB [88].…”
Section: Drug-susceptible Tb [71]mentioning
confidence: 99%
“…Sutezolid (PNU100480) and AZD5847 are other, newer oxazolidinones that are also in phase II studies [87]. Some preliminary evidence suggests that these drugs may have a better bioavailability and may be better tolerated by patients [88]. In addition, the two fluoroquinolones moxifloxacin and gatifloxacin are currently in phase III clinical trials [87].…”
Section: Drug-susceptible Tb [71]mentioning
confidence: 99%
“…Limited but promising data are available for diarylquinolones. These drugs reduce adenosine triphosphate (ATP) levels by selectively inhibiting the mycobacterial ATP synthase [87][88][89]. However, they do have little to no effect on other bacteria or eukaryotes.…”
The history of tuberculosis (TB) is intricately connected to the history of humanity. The disease is considered one of the oldest infectious diseases afflicting mankind. Its history is that of colorful, often vibrant descriptions and interpretations, in the attempt of human societies to demystify the origins, causality, and course of this grave and lethal disease, and in the ultimate pursuit of finding a cure. The discovery of the tubercle bacillus on March 24 th 1882, by Robert Koch, led to an unprecedented increase in international research efforts, ultimately resulting in the development of a vaccine and many potent antimicrobial agents and treatment regimens. However, the course of history is often not without some irony, commonly perceived as being unpredictable by those who find themselves immersed in history's path. In this sense, and despite the advances that were made in diagnostics and treatment during the past 70 years, TB continues to challenge mankind on numerous levels even today. The most recent emergence of multidrug-resistant and extensively-drug-resistant strains of Mycobacterium tuberculosis is only a small but significant reflection of the ongoing challenges in the attempt of eradicating this disease. Here we provide a review of the historic aspects of TB leading to a discussion of the current state of the approach to antituberculous treatment, including the aspects of microbiology, diagnostics, antimicrobial therapy, and public health.
“…3 This is the first time in the modern history of TB control that new drugs have been developed and approved for the treatment of MDR-TB, and the first time that national and international TB stakeholders have tried to introduce new drugs in a programmatic way. 4 Uptake of these drugs as part of MDR-TB treatment, however, has not kept pace with the need for these drugs, even in settings where resistance or intolerance to second-line drugs is common or where treatment outcomes are poor. 5 Multiple early barriers to programmatic introduction of new drugs have been identified, including lack of technical expertise and guidance, confusion about pharmacovigilance requirements, challenges with registration and import, and difficulties in obtaining the other medications needed for successful treatment outcomes.…”
SUMMARYBACKGROUND-For the first time in almost 50 years, there are new drugs available for the treatment of tuberculosis (TB), including bedaquiline (BDQ) and delamanid (DLM). The rate of introduction, however, has not kept pace with patient needs. It is estimated that as many as 23% of multidrug-resistant TB (MDR-TB) patients have an indication for receiving BDQ. As this is the first time the MDR-TB community is introducing new medications, it is important to understand how implementation can be developed in a variety of settings.
The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug‐resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four‐drug treatment regimen was introduced 40 years ago but the emergence of multidrug‐resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti‐TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug‐target interactions, and their structure‐activity relationship.
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