Old Drugs, New Purpose: Retooling Existing Drugs for Optimized Treatment of Resistant Tuberculosis (original) (raw)
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New anti-tuberculosis drugs and regimens: 2015 update
ERJ Open Research, 2015
Over 480 000 cases of multidrug-resistant (MDR) tuberculosis (TB) occur every year globally, 9% of them being affected by extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The treatment of MDR/XDR-TB is unfortunately long, toxic and expensive, and the success rate largely unsatisfactory (<20% among cases with resistance patterns beyond XDR).The aim of this review is to summarise the available evidence-based updated international recommendations to manage MDR/XDR-TB, and to update the reader on the role of newly developed drugs (delamanid, bedaquiline and pretomanid) as well as repurposed drugs (linezolid and meropenem clavulanate, among others) used to treat these conditions within new regimens.A nonsystematic review based on historical trials results as well as on recent literature and World Health Organization (WHO) guidelines has been performed, with special focus on the approach to managing MDR/XDR-TB.The new, innovative global public health intervention...
The challenge of the new tuberculosis drugs
Presse medicale (Paris, France : 1983), 2017
Tuberculosis (TB) continues to cause more deaths worldwide than any other single infectious disease. Even though tuberculosis appears to be decreasing in incidence globally for some time, the proportion of drug resistance is increasing, contributing to greater complexity, morbidity and mortality as well as cost. Since the advent of rifampicin in the 1960s, and the implementation of standard quadruple anti-tuberculosis regimen in the late 1970s, no new drugs have been changed the first line regimen. This regimen is effective however it is pill burden, and duration has not received investment and innovation. Drug-resistant regimens are long and frequently poorly tolerated due to significant toxicity. This review is an update on what is new in the treatment of drug-susceptible and drug-resistant tuberculosis, new TB drugs currently being used and studied in clinical trials are also mentioned. Fortunately, there have been many significant advances in this field in recent years. The hori...
Clinical management of drug resistant tuberculosis
Asian Journal of Medical Sciences, 2014
Despite the introduction 40 years ago of the inexpensive and effective four-drug (isoniazid, rifampicin, pyrazinamide and ethambutol) treatment regimen, tuberculosis (TB) continues to cause considerable morbidity and mortality worldwide. This is because of development of drug resistance in tuberculosis strains, usually called as MDR/XDR-TB. Consequently, novel drugs and regimens for management of these drug resistant TB forms are emerging. Such regimens probably utilize both repurposed drugs and new chemical drugs. This article covers current concepts and recent advances in TB drug discovery and development. An updated review of the mechanisms of action and resistance of the main old and new anti-tuberculosis agents has been described. The consensus statements from RNTCP for management of MDR/XDR-TB have also been discussed.
WHAT'S NEW IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS? (Atena Editora)
WHAT'S NEW IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS? (Atena Editora), 2023
Introduction: The current Tuberculosis epidemic represents a major public health problem. The issue gained prominence due to the increasing incidence of Mycobacterium tuberculosis strains resistant to first-line antituberculosis agents, posing a threat to disease control and management strategies. Objectives: To identify in the literature an overview of the current evidence on the management of multidrug-resistant tuberculosis. Methodology: A bibliographic review was carried out, through research in the SciELO databases, the Virtual Health Library and in data repositories. 4 original articles and 1 document made available by the Ministry of Health, published from 2018 to 2022, were selected. Descriptors used: MDR-TB, Multidrug-resistant Tuberculosis, Antituberculous agents. Results and Discussion: Multidrug-resistant Tuberculosis (MDR-TB) is described by resistance to the drugs rifampicin and isoniazid, used as a standard therapeutic scheme. The disease poses challenges in its treatment, such as a high failure rate and high risk of adverse events, mainly due to the lack of standardization and global regulation of the drugs used. Currently, excluding restrictions, treatment lasts for 8 months using capreomycin associated with levofloxacin, terizidone, ethionamide and pyrazinamide, followed by 10 months of treatment with levofloxacin associated with terizidone and ethionamide. Bedaquiline (BDQ), a diarylquinoline with bactericidal and sterilizing action, is recommended by the World Health Organization (WHO) in long-term regimens and in combination with three other effective drugs. The proposed administration is oral, aiming to optimize treatment outcomes and reduce toxicity associated with injectable drugs. A retrospective observational study conducted in 15 countries reported the outcomes of 428 cases treated with BDQ-containing regimens. The bacilloscopy and sputum culture conversion rates achieved at the end of treatment were 88.7% and 91.2%, respectively; the success rate in the cohort as a whole was 77%. Delamanid, a drug from the nitroimidazole class with bactericidal action, is recommended under the same conditions described for BDQ, prescribed when drugs from the previous groups cannot be used. Recent evidence suggests that the bedaquiline-delamanid combination is well tolerated in cases where few treatment options are available. The use of beta-lactam antibiotics associated with a beta-lactamase inhibitor, such as carbapenems associated with clavulanic acid, proved to be a therapeutic alternative. The combination showed a potent effect against M. tuberculosis - the cohorts performed had a success rate between 57.3% and 80.3%. However, the use of carbapenems is restricted to patients with severe presentation of the disease and therapeutic failure in second-line treatment. Factors such as high costs and lack of oral formulations contribute to their limited use. Conclusion: Through the study carried out, it was possible to confirm the challenges of MDR-TB therapy. Drugs such as delamanid, bedaquiline and carbapenems proved to be promising alternatives for the treatment of MDR-TB, demonstrating the importance of searching for new therapeutic strategies that aim not only to improve the current scenario of the disease, but also to improve the quality of care. patient's life and adherence to treatment.
Journal of biomedical research & environmental sciences, 2022
Drug-Resistant Tuberculosis (DR-TB) causes high mortality and morbidity rates globally. DR-TB and COVID-19 pandemic are posing a major risk to global public health and economic security, and are jeopardizing efforts in the control, prevention and elimination of TB globally. Mycobacterium tuberculosis (MTB) has continued to evolve resistance to anti-TB drugs. Different types of DR-TB have been defi ned and they include; mono drug-resistant TB, Multi Drug-Resistant TB (MDR-TB), poly drug-resistant TB, pre-Extensively Drug-Resistant TB (pre-XDR TB), Extensively Drug-Resistant TB (XDR-TB), Extremely Drug-Resistant TB (XXDR-TB), and Totally Drug-Resistant TB (TDR-TB). DR-TB is caused by several factors which include: non-adherence, poor compliance, low effi cacy anti-TB drugs, delayed diagnosis, interrupted supply, stock-outs, inadequate infection control, HIV coinfection, spontaneous mutations, and chromosomal replication errors. Global TB targets have gone off-track and years of progress reversed due to DR-TB and the COVID-19 pandemic. Treatment failure, death and costs incurred are higher among patients suffering from DR-TB than among those with susceptible TB. For this reason, susceptible TB needs to be diagnosed quickly and treated effectively to prevent its progression to DR-TB. Treatment for susceptible TB requires the use of fi rst-line anti-TB drugs; rifampicin, isoniazid, pyrazinamide, and ethambutol. While DR-TB is treated using the second-and third-line anti-TB drugs. Effective treatment of TB is dependent on: prompt and accurate diagnosis of TB and recognition of drug-resistance; adherence to treatment; robust contact tracing and prophylactic treatment of TB contacts; and screening for TB infection in high-risk groups.
Journal of Infectious Diseases, 2013
Background. Treatment of multidrug-resistant or extensively drug-resistant tuberculosis (DR-tuberculosis) is challenging because commonly used second-line drugs are poorly efficacious and highly toxic. Although World Health Organization group 5 drugs are not recommended for routine use because of unclear activity, some may have untapped potential as more efficacious or better tolerated alternatives. Methods. We conducted an exhaustive review of in vitro, animal, and clinical studies of group 5 drugs to identify critical research questions that may inform their use in current treatment of DR-tuberculosis and clinical trials of new DR-tuberculosis regimens. Results. Clofazimine may contribute to new short-course DR-tuberculosis regimens. Beta-lactams merit further evaluation-specifically optimization of dose and schedule. Linezolid appears to be effective but is frequently discontinued due to toxicity. Thiacetazone is too toxic to warrant further evaluation. Mycobacterium tuberculosis has intrinsic inducible resistance to clarithromycin. Conclusions. Clofazimine and beta-lactams may have unrealized potential in the treatment of DR-tuberculosis and warrant further study. Serious toxicities or intrinsic resistance limit the utility of other group 5 drugs. For several group 5 compounds, better understanding of structure-toxicity relationships may lead to better-tolerated analogs.
Recent Trends in Treatment of Multidrug Resistant-Tuberculosis-A Review
Mycobacterial Diseases, 2017
Drug resistance is reduction in effectiveness of an anti-microbial agents used in inhibiting the microorganisms or curing a disease. Mycobacterium tuberculosis is responsible for causing tuberculosis can acquire multiple drug resistance by not responding to Isoniazid and Rifampicin the two most powerful anti-TB agents. The complications of drug resistance in TB elevates due to some of the risk factors like inadequate treatment compliance, noncompliance of the patients to the treatment. Proper diagnosis of the disease and switching to modified drug therapy may improve the treatment outcome. The drug treatment involves usage of combination of drugs Isoniazid, Rifampicin, Ethambutol along with other antimicrobial agents, and nutritional therapy, immunotherapy. In this review we discussed about the occurrence, treatment of multi drug resistance tuberculosis along with drugs under trials and nutritional requirements.
Tuberculosis Clinical Trial Update and the Current Anti-Tuberculosis Drug Portfolio
Tuberculosis (TB), an ongoing public health threat, is worsened by the emergence of drug resistance. With an estimated 630000 cases per year of multidrug resistant (MDR)-TB, and 9% of those being extensively drug resistant (XDR)-TB, there is an urgent need for new and more effective anti-TB drugs. New TB treatment regimens should be able to shorten the duration of therapy that currently takes at least six months. The non-compliance with this long treatment duration is one of the reasons for the development of drug resistance. In spite of the difficulties and alleged lack of interest from the pharmaceutical industry for the discovery and development of new antibiotics, several new or repurposed drugs are being evaluated in clinical trials. This review article summarizes the information available and presents an update on the drugs currently in clinical trials for TB and briefly introduces some new compounds in pre-clinical development.