Journal articles: 'New TB drugs'

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Pandey, Shilpika, Isha Soni, Neha Topno, Arunava Dasgupta, and Sidharth Chopra. "Current Approaches for New TB Drugs." Current Respiratory Medicine Reviews 10, no. 2 (November 14, 2014): 88–96. http://dx.doi.org/10.2174/1573398x10666140813201210.

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Soedarsono, Soedarsono. "Tuberculosis: Development of New Drugs and Treatment Regimens." Jurnal Respirasi 7, no. 1 (January 30, 2021): 36. http://dx.doi.org/10.20473/jr.v7-i.1.2021.36-45.

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Tuberculosis (TB) still becomes a public health crisis. Drug-resistant TB (DR-TB) becomes a concern as the increasing DR-TB cases in countries with high TB burden. The 2017 World Health Organization (WHO) guideline recommended a combination of TB treatment consisting of 2 months of intensive phase with isoniazid (H), rifampisin (R), pyrazinamid (Z), and ethambutol (E), followed by 4 months of continuation phase with HR daily. WHO has updated DR-TB treatment guidelines several times. In 2016, WHO recommended shorter regimen and individual regimen based on certain conditions. The most updated 2020 WHO guideline recommended the short regimen consisting of all oral drugs as well as changes in the grouping of medicines used in DR-TB regimens in longer/individual regimens. Bedaquiline, delamanid, pretomanid, and sutezolid are new drugs which have been studied for their uses as anti-TB drugs (ATD). Bedaquilin and delamanid, which have passed phase 3 trials, have been approved and recommended by WHO for DR-TB treatment. Repurposed drugs have been used for DR-TB treatment during the time of evaluation of drugs list and regimens for DR-TB treatment. Fluoroquinolones, clofazimine, linezolid, carbapenem, amoxicillin/clavulanic acid are repurposed drugs. TB and DR-TB management will be updated at any time, based on the latest findings in studies, to evaluate and improve the effectiveness of current treatments. Prevention of active TB disease by the treatment of latent TB infection (LTBI) is also a critical component of the end TB strategy by WHO. Therefore, the development of new drugs for the LTBI treatment is also needed.

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D'Ambrosio, Lia, Rosella Centis, Giovanni Sotgiu, Emanuele Pontali, Antonio Spanevello, and Giovanni Battista Migliori. "New anti-tuberculosis drugs and regimens: 2015 update." ERJ Open Research 1, no. 1 (May 2015): 00010–2015. http://dx.doi.org/10.1183/23120541.00010-2015.

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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 interventions, recently approved by WHO and known as the “End TB Strategy”, support the vision of a TB-free world with zero death, disease and suffering due to TB. Adequate, universally accessed treatment is a pre-requisite to reach TB elimination. New shorter, cheap, safe and effective anti-TB regimens are necessary to boost TB elimination.

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Seung, K. J., U. Khan, F. Varaine, S. Ahmed, M. Bastard, S. Cloez, D. Damtew, et al. "Introducing new and repurposed TB drugs: the endTB experience." International Journal of Tuberculosis and Lung Disease 24, no. 10 (October 1, 2020): 1081–86. http://dx.doi.org/10.5588/ijtld.20.0141.

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In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015–2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.

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Mignani, Serge, Rama Tripathi, Liang Chen, Anne-Marie Caminade, Xiangyang Shi, and Jean-Pierre Majoral. "New Ways to Treat Tuberculosis Using Dendrimers as Nanocarriers." Pharmaceutics 10, no. 3 (July 26, 2018): 105. http://dx.doi.org/10.3390/pharmaceutics10030105.

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Tuberculosis (TB) is a contagious infection that usually attacks not only the lungs, but also brain and spine. More than twenty drugs have been developed for the treatment of TB, but most of them were developed some years ago. They are used in different combinations. Isoniazid and Rifampicin are examples of the five first line TB drugs, whereas, for instance, Levofloxacin, Kanamycin and Linezolid belong to the second line drugs that are used for the treatment of drug resistant TB. Several new bicyclic nitroimidazoles (e.g., Delamanid) without mutagenic effects were developed. New TB drugs need to provide several main issues such as more effective, less toxic, and less expensive for drug resistant TB. Besides polymeric, metal-based nanoparticles, polymeric micelles and polymers, dendrimer nanostructures represent ideal delivery vehicles and offer high hopes for the future of nanomedicine. In this original review, we present and analyze the development of anti-TB drugs in combination with dendrimers. Few articles have highlighted the encapsulation of anti-TB drugs with dendrimers. Due to their unique structure, dendrimers represent attractive candidates for the encapsulation and conjugation of other anti-TB drugs presenting important drawbacks (e.g., solubility, toxicity, low bioavailability) that hinder their development, including clinic trials.

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Vilchèze, Catherine. "Mycobacterial Cell Wall: A Source of Successful Targets for Old and New Drugs." Applied Sciences 10, no. 7 (March 27, 2020): 2278. http://dx.doi.org/10.3390/app10072278.

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Eighty years after the introduction of the first antituberculosis (TB) drug, the treatment of drug-susceptible TB remains very cumbersome, requiring the use of four drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) for two months followed by four months on isoniazid and rifampicin. Two of the drugs used in this “short”-course, six-month chemotherapy, isoniazid and ethambutol, target the mycobacterial cell wall. Disruption of the cell wall structure can enhance the entry of other TB drugs, resulting in a more potent chemotherapy. More importantly, inhibition of cell wall components can lead to mycobacterial cell death. The complexity of the mycobacterial cell wall offers numerous opportunities to develop drugs to eradicate Mycobacterium tuberculosis, the causative agent of TB. In the past 20 years, researchers from industrial and academic laboratories have tested new molecules to find the best candidates that will change the face of TB treatment: drugs that will shorten TB treatment and be efficacious against active and latent, as well as drug-resistant TB. Two of these new TB drugs block components of the mycobacterial cell wall and have reached phase 3 clinical trial. This article reviews TB drugs targeting the mycobacterial cell wall in use clinically and those in clinical development.

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Leibert, Eric, and William N. Rom. "New drugs and regimens for treatment of TB." Expert Review of Anti-infective Therapy 8, no. 7 (July 2010): 801–13. http://dx.doi.org/10.1586/eri.10.60.

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Elger, B. S., F. Mirzayev, S. Afandiyev, and E. Gurbanova. "Ethical issues in tuberculosis screening and the use of new drugs for prisoners." International Journal of Tuberculosis and Lung Disease 24, no. 5 (May 1, 2020): 57–60. http://dx.doi.org/10.5588/ijtld.17.0899.

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SETTING: Prisons are known to have extremely high tuberculosis (TB) and multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB prevalence and poor treatment outcomes.OBJECTIVE: To examine the screening and M/XDR-TB treatment with new TB drugs in prisons from the perspective of international ethical and legal requirements.DESIGN: WHO recommendations on TB screening in prisons and M/XDR-TB treatment as well as the international human rights law on prisoners were analysed.RESULTS: Prisoners have a human right to access at least the same level of TB care as in their communities. Screening for TB in prisons, which may run contrary to a given individual's choice to be tested, may be justified by the positive obligation to prevent other prisoners from contracting a possibly deadly disease. Introduction of new TB drugs in prisons is necessary, ethically sound and should start in parallel with introduction in a civilian sector in strict compliance with the WHO recommendations.CONCLUSION: Access to screening for TB, as well as effective treatment according to WHO recommendations, must be ensured by countries on the basis of international human rights conventions.

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Bernal, O., R. Lopez, E. Montoro, P. Avedillo, K. Westby, and M. Ghidinelli. "Introduction and scaling up of new drugs for drug-resistant TB: experiences from the Americas." International Journal of Tuberculosis and Lung Disease 24, no. 10 (October 1, 2020): 1058–62. http://dx.doi.org/10.5588/ijtld.20.0111.

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The number of multidrug-resistant tuberculosis (MDR-TB) cases reported in the Americas has increased by 21.2%, from 3737 in 2016 to 4791 in 2018. The WHO has been recommending changes on the treatment of DR-TB, moving from long-duration treatment with injectables to a short oral regimen with new drugs such as bedaquiline (BDQ) and delamanid (DLM), in selected cases and only under programmatic conditions. Injectables are no longer recommended by the WHO due to lower efficacy and the increasing seriousness of adverse events. The introduction of new oral drugs for DR-TB received a boost with a global donation of BDQ to some eligible countries, which continues with the countries purchasing drugs through the Pan American Health Organization Strategic Fund. The main challenges in the scaling up of new drugs for DR-TB include low DR-TB detection rate, the slow pace in transitioning to molecular testing and delays in the introduction of new oral short regimens for MDR-TB. The Americas need to accelerate the scale up of new oral treatments, improve detection rates, increase molecular diagnosis of resistance, and ensure the registration and introduction of the shorter treatment regimen in national MDR-TB guidelines.

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De Souza, Marcus Vinicius Nora. "Plants and Fungal Products with Activity Against Tuberculosis." Scientific World JOURNAL 5 (2005): 609–28. http://dx.doi.org/10.1100/tsw.2005.80.

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Tuberculosis (TB) is becoming an ever more serious worldwide problem. This contagious disease kills four people every minute somewhere in the world and accounts for more than 2 million deaths per year. Due to the rapid spread of TB strains resistant to all the major anti-TB drugs on the market, and the association of TB with human immunodeficiency virus (HIV) infection in AIDS, we urgently need to develop new drugs to fight against TB. In this context, due to the importance of nature in the development of new drugs, the aim of the present review is to highlight a series of new and promising anti-TB agents derived from plants and fungi discovered between 2001 and 2005.

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MARCHETTI, CHIARA, DANIEL S. H. CHAN, ANTHONY G. COYNE, and CHRIS ABELL. "Fragment-based approaches to TB drugs." Parasitology 145, no. 2 (November 2, 2016): 184–95. http://dx.doi.org/10.1017/s0031182016001876.

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SUMMARYTuberculosis is an infectious disease associated with significant mortality and morbidity worldwide, particularly in developing countries. The rise of antibiotic resistance in Mycobacterium tuberculosis (Mtb) urgently demands the development of new drug leads to tackle resistant strains. Fragment-based methods have recently emerged at the forefront of pharmaceutical development as a means to generate more effective lead structures, via the identification of fragment molecules that form weak but high quality interactions with the target biomolecule and subsequent fragment optimization. This review highlights a number of novel inhibitors of Mtb targets that have been developed through fragment-based approaches in recent years.

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Huynh, Julie, and Ben J. Marais. "Multidrug-resistant tuberculosis infection and disease in children: a review of new and repurposed drugs." Therapeutic Advances in Infectious Disease 6 (January 2019): 204993611986473. http://dx.doi.org/10.1177/2049936119864737.

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The World Health Organization estimates that 10 million new cases of tuberculosis (TB) occurred worldwide in 2017, of which 600,000 were rifampicin or multidrug-resistant (RR/MDR) TB. Modelling estimates suggest that 32,000 new cases of MDR-TB occur in children annually, but only a fraction of these are correctly diagnosed and treated. Accurately diagnosing TB in children, who usually have paucibacillary disease, and implementing effective TB prevention and treatment programmes in resource-limited settings remain major challenges. In light of the underappreciated RR/MDR-TB burden in children, and the lack of paediatric data on newer drugs for TB prevention and treatment, we present an overview of new and repurposed TB drugs, describing the available evidence for safety and efficacy in children to assist clinical care and decision-making.

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Meena, Jaishree, and Laxman S. Meena. "Scope and Perspectives of New TB Drugs and Vaccines." American Journal of Infectious Diseases 11, no. 3 (March 1, 2015): 63–73. http://dx.doi.org/10.3844/ajidsp.2015.63.73.

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Bark, Charles M., Jennifer J. Furin, and John L. Johnson. "Approaches to clinical trials of new anti-TB drugs." Clinical Investigation 2, no. 4 (April 2012): 359–70. http://dx.doi.org/10.4155/cli.12.22.

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Sutherland, Stephani. "Getting inside the bug: New targets for TB drugs." Drug Discovery Today 10, no. 10 (May 2005): 679–80. http://dx.doi.org/10.1016/s1359-6446(05)03454-9.

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Silva, Denise Rossato, Margareth Dalcolmo, Simon Tiberi, Marcos Abdo Arbex, Marcela Munoz-Torrico, Raquel Duarte, Lia D’Ambrosio, et al. "New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis." Jornal Brasileiro de Pneumologia 44, no. 2 (April 2018): 153–60. http://dx.doi.org/10.1590/s1806-37562017000000436.

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ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the “white plague”, and promising results are being reported.

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Tiberi, Simon, Emanuele Pontali, Marina Tadolini, Lia D’Ambrosio, and Giovanni Battista Migliori. "Challenging MDR-TB clinical problems – The case for a new Global TB Consilium supporting the compassionate use of new anti-TB drugs." International Journal of Infectious Diseases 80 (March 2019): S68—S72. http://dx.doi.org/10.1016/j.ijid.2019.01.040.

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Nikolenko, N. Yu, D. А. Kudlay, and N. P. Doktorova. "Pharmacoepidemiology and pharmacoeconomics of multidrug- and extensively drug-resistant tuberculosis." FARMAKOEKONOMIKA. Modern Pharmacoeconomic and Pharmacoepidemiology 14, no. 2 (July 27, 2021): 235–48. http://dx.doi.org/10.17749/2070-4909/farmakoekonomika.2021.089.

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Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is a current problem worldwide. Currently, special attention is paid to the possibility of using new high-cost chemotherapy regimens in the treatment of MDR/XDR-TB. Numerous studies have shown that, from a clinical point of view, the effectiveness of MDR/XDR-TB therapy increases with the inclusion of bedaquiline, delamanid, linezolid, fluoroquinolones (moxifloxacin, levofloxacin), and pretomanid. At the same time, there is an assumption that the use of new and repurposed anti-tuberculosis drugs (ATDs) may be associated with an increase in overall costs. This paper demonstrates the potential of pharmacoepidemiology and pharmacoeconomics to evaluate the widespread introduction of new anti-tuberculosis drugs (ATDs), taking into account all the typical features of MDR/XDR-TB therapy. The authors analyzed studies of pharmacoeconomic feasibility of using expensive drugs in treatment regimens of pulmonary tuberculosis patients with MDR/XDR pathogen. It was shown that the use of chemotherapy regimens containing new high-cost and highly effective drugs (moxifloxacin, linizolid, and bedaquiline) in rational combinations with other drugs of the basic and reserve series, selected concerning drug resistance of the pathogen, is associated with a significant economic effect. From the applicability of pharmacoeconomic analysis point of view, the introduction of short-term MDR-TB treatment regimens is also a promising direction in phthisiology. The key link to achieve effective MDR/XDR-TB treatment is the use of new drugs. Considering the specificity of pharmacoeconomic analysis in phthisiology and results of existing clinical and economic studies, the authors have formed recommendations aimed at a more complete realization of pharmacoeconomic analysis potential in MDR- and XDR-TB treatment.

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Sachdeva, K. S., N. Arora, R. Solanki, R. Singla, R. Sarin, A. Bhatnagar, A. Khanna, et al. "Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens." International Journal of Tuberculosis and Lung Disease 24, no. 10 (October 1, 2020): 1067–72. http://dx.doi.org/10.5588/ijtld.20.0136.

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BACKGROUND: Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE: To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN: In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS: An interim analysis reflected earlier and better culture conversion rates: 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION: The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.

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Goldberg, Stefan, and Philip LoBue. "Pulmonary Tuberculosis: Focus on the Fluoroquinolones." Clinical Medicine Insights: Therapeutics 2 (January 2010): CMT.S1974. http://dx.doi.org/10.4137/cmt.s1974.

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Fluoroquinolone antibiotics are relatively new drugs in anti-tuberculosis (TB) treatment, with the potential to become the first new class of drugs to be recommended for routine treatment since rifamycins in the 1960s. Later generation fluoroquinolones, including levofloxacin, gatifloxacin, and moxifloxacin have been found to be safe and well-tolerated in observational studies and phase 2 clinical trials, except for a risk of severe dysglycemias with gatifloxacin. These drugs currently are used as second-line agents in treatment of TB cases with drug resistance and drug intolerance, and empirically in treatment of infected contacts of patients with multi-drug resistant TB. Widespread use of fluoroquinolones for treatment of community acquired pneumonia and other bacterial infections is leading to the emergence and spread of strains of Mycobacterium tuberculosis that are fluoroquinolone-resistant, putting at risk the potential effectiveness of these drugs against TB. Clinical trials are under way to determine whether fluoroquinolone-based treatment regimens can shorten the duration of TB therapy. The ultimate contributions of fluoroquinolones to TB control remain to be determined.

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Clain, Jeremy M., and Patricio Escalante. "Novel Treatments for Drug-Resistant Tuberculosis." Clinical Medicine Insights: Therapeutics 8 (January 2016): CMT.S18560. http://dx.doi.org/10.4137/cmt.s18560.

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Drug resistance has emerged as a major obstacle to global control of tuberculosis (TB). Treatment with currently available medications requires prolonged courses of numerous drugs, many of which are associated with significant adverse effects. New drugs are urgently needed to meet the challenge posed by drug-resistant TB, in order to relieve the burden that drug resistance has placed on individual patients and health systems. Fortunately, many new drugs have been developed for the treatment of drug-resistant TB in recent years. The new antimycobacterial agents are derived from various medication classes, work by means of an assortment of mechanisms of action, and are at differing phases of development. This review provides a survey of the most promising new agents, in order to promote familiarity with these emerging drugs and compounds.

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Ogunbanjo, Gboyega A. "Multi-drug-resistant tuberculosis (MDR-TB): Current situation in South Africa." South African Family Practice 59, no. 2 (May 11, 2017): 5. http://dx.doi.org/10.4102/safp.v59i2.4679.

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Multi-drug-resistant tuberculosis (MDR-TB) is a form of tuberculosis (TB) infection which is resistant to treatment with at least two of the most powerful first-line anti-TB drugs, namely isoniazid and rifampicin. Globally, MDR-TB caused an estimated 480 000 new TB cases and 250 000 deaths in 2015 and accounted for 3.3% of all new TB cases worldwide.1 MDR-TB, or rifampicin-resistant TB, causes 3.9% of new TB cases and 21% of previously treated TB cases, and most MDR-TB cases occur in South America, southern Africa, India, China, and the former Soviet Union.1

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Usacheva, Natalia E., Vasiliy E. Novikov, Tatyana V. Myakisheva, Nadezhda A. Pavluchenkova, and Elena V. Trun. "Structural changes in the Russian pharmaceutical market of anti-tb drugs." Reviews on Clinical Pharmacology and Drug Therapy 18, no. 3 (October 14, 2020): 245–54. http://dx.doi.org/10.17816/rcf183245-254.

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In Russia, the epidemic situation for tuberculosis has stabilized with a tendency to improvement, according to the dynamics of the main indicators for the disease. However, the problem of tuberculosis infection is still far from being resolved, which is largely due to the development of drug resistance of the infectious agent to the main anti-TB drugs. The purpose of the study is to form macro-structures of the Russian market of anti-TB drugs for 2008 and 2018 and analyze the dynamics of their structural changes. Materials and methods. The State registers of medicines of the Russian Federation for 2008 and 2018 were analyzed. Into account were taken following characteristics of the range: the number of registered anti-TB drugs, dosage forms, dosages, manufacturers, and the number of combined anti-TB drugs. The necessary data was obtained using the content analysis method. The results of the study allowed us to build macro-structures of the Russian market of anti-TB drugs and compare the indicators in the dynamics over 10 years. Results. Over the past 10 years, about 500 anti-TB drugs have been registered and re-registered in the Russian Federation. The range of the selected segment was supplemented by the 3rd new series, which according to 2018 included 166 (30.0%) drugs, taking into account all dosage forms and dosages. The group of anti-TB drugs of the 2nd series in 2018 was the leader in the selected segment (52.2%) and there was a tendency for its growth. In the structure of the assortment of medicinal forms of anti-TB drugs, tablet drugs prevailed (43.5%). The production vector has shifted towards domestic manufacturers. The share of new drugs put into circulation in 2008-2018 was 37%. The nomenclature of the Russian anti-TB market corresponds to international recommendations and contains the main groups of drugs. Conclusion. Analysis of the segment of anti-TB drugs in the domestic pharmaceutical market showed that the phthisiological service has a sufficient range of drugs for the treatment of tuberculosis infection, including those with drug resistance of the pathogen. This allows to personalize therapy based on the stage and severity of the disease, the functional characteristics of the patients body, and the sensitivity of the pathogen to chemotherapy.

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Jain, Sonal, and Arun Kumar. "Clinical management of drug resistant tuberculosis: A comprehensive review." Asian Journal of Medical Sciences 5, no. 3 (February 24, 2014): 1–9. http://dx.doi.org/10.3126/ajms.v5i3.9698.

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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.Asian Journal of Medical Science, Volume-5(3) 2014: 1-9DOI: http://dx.doi.org/10.3126/ajms.v5i3.9698

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Suryoiman Winoto, Eden, and Didi Candradikusuma. "Shorter All-oral Bedaquiline-containing MDR-TB Regimen : The Backgrounds & Implementations." Clinical and Research Journal in Internal Medicine 2, no. 1 (January 1, 2021): 142–57. http://dx.doi.org/10.21776/ub.crjim.2021.002.01.6.

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The continuing spread of Multidrug-Resistant Tuberculosis (MDR-TB), which is defined as TB that shows resistance to both isoniazid and rifampicin, become one of the most urgent and difficult challenges in TB control. In Indonesia, the estimated total DR-TB case incidence of 24,000 or 8.8/100,000 population (2.4% of total new TB patients). The first-ever MDR-TB treatment guideline published by WHO required a long duration (up to 20–24 months) and contained toxic second-line drugs with less effective & unfavorable outcomes. About ten years ago, a short regimen lasting nine instead of 20 months, called “Bangladesh regimen”, revolutionized MDR-TB treatment. The advent of rapid molecular diagnostic tests, discoveries of new and repurposed drugs, promising results based on trials and meta-analysis had prompted WHO to update its guidelines. Notably, drugs such as bedaquiline and clofazimine are now strongly recommended for the treatment of MDR-TB. At the same time, older injectables drugs have been downgraded due to poor effectiveness and side-effect profiles. In 2019, based on the programmatic data from the shorter all-oral bedaquiline-containing regimen implemented routinely in South Africa, WHO revised its recommendations on the use of a standardized shorter regimen. Based on the analysis, WHO affirmed its conditional recommendation for the shorter all-oral bedaquiline-containing MDR -TB regimen to be offered as a treatment option to MDR -TB patients who satisfy the eligibility criteria. The implementation of this all-oral shorter regimen is expected to improve the programmatic management of the MDR-TB worldwide.

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Palucci, Ivana, and Giovanni Delogu. "Host Directed Therapies for Tuberculosis: Futures Strategies for an Ancient Disease." Chemotherapy 63, no. 3 (2018): 172–80. http://dx.doi.org/10.1159/000490478.

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The emergence and spread of drug-resistant strains of Mycobacterium tuberculosis is worsening the global threat of tuberculosis (TB). There is a need and urgency for the development of new treatments for TB, for the management of drug resistant TB (MDR-TB) and for improved regimens against drug-susceptible TB, with the goal of reducing toxicity and length of therapy that will boost patience compliance. The paucity of new drugs is a major obstacle to design new regimens while host-directed therapies (HDTs) are emerging as a promising area of research and are opening new avenues to fight TB. In this review, we discuss examples of potentially promising strategies aimed at improving the host response to M. tuberculosis, and argue how a better understanding of TB pathogenesis, with the fine characterization of the immunological mediators involved, may pave the way for the design of new therapies, the identification of new drugs or the repurposing of some already in use for other diseases. We emphasize that any HDTs shall be included as adjunct therapy to the drug-combination regimens already in use for TB, with the goal to reduce tissue damage and immunopathology and enhance bacterial clearance. We anticipate that the benefits of HDTs against TB will be highest against MDR-TB, where the activity of current regimens is poor and the cost high.

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Nikonenko, Boris V., Rowena Samala, Leo Einck, and Carol A. Nacy. "Rapid, Simple In Vivo Screen for New Drugs Active against Mycobacterium tuberculosis." Antimicrobial Agents and Chemotherapy 48, no. 12 (December 2004): 4550–55. http://dx.doi.org/10.1128/aac.48.12.4550-4555.2004.

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ABSTRACT We evaluated the use of a simple and easy-to-obtain potential marker of tuberculosis (TB) drug efficacy, body weight, and correlated weight loss or gain with the number of CFU of Mycobacterium tuberculosis in lungs and spleens of infected mice. C3H mice were infected intravenously with 106 CFU of virulent M. tuberculosis H37Rv, and body weight was evaluated for several weeks after infection. At day 20, infected untreated mice consistently lost more than 25% of their body weight. Chemotherapy with selected orally active anti-TB drugs was initiated 7 days following infection and continued for 13 days. Drugs that were administered daily by gavage included isoniazid (INH), ethambutol (EMB), rifampin (RIF), and moxifloxacin (MXF). At the most effective doses, each of these drugs inhibited bacterial growth and abolished infection-induced body weight loss. Chemotherapy with 1/10 the standard dose of INH determined in accepted long-term murine models of TB also prevented body weight loss, while chemotherapy with 1/10 the standard dose of RIF did not. With only 2 weeks of chemotherapy, we observed a good reverse correlation between CFU in lung or spleen and body weight of mice. The simple measurement of weight in TB-infected drug-treated mice required only a weight balance, and go/no-go drug efficacy data was available on day 20 without the necessity of prolonged drug treatment and long (3 weeks or more) in vitro culture times to obtain organ CFU values.

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Liu, Zhao, Lijun Shen, Fan Zhang, Tiantian Du, and Yuehua Liu. "PP382 Research On The Second-Line Anti-Tuberculosis Drugs Supply Based On Stakeholder Theory Of China." International Journal of Technology Assessment in Health Care 36, S1 (December 2020): 31. http://dx.doi.org/10.1017/s026646232000166x.

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IntroductionChina is one of the twenty-seven countries with a high burden of Multidrug-resistant tuberculosis (MDR-TB) in the world. Of the new TB patients in China in 2017, about 63,000 are MDR-TB patients, accounting for one-third of the number of new MDR-TB patients worldwide.In the latest “China's 13th Five-Year Plan” national TB prevention and control plan promulgated in 2017, it is clearly emphasized that all regions should gradually incorporate TB into the payment catalogue of special outpatient medical insurance, according to local conditions. However, for this special group of MDR-TB patients, there is no specialized prevention and control policy at the national level, and there are also blind spots in the medical security policy.Responding to the drug needs of MDR-TB patients, it is necessary to provide patients with stable and affordable second-line anti-TB drugs. It is also necessary to understand the overall drug demand for second-line drugs nationwide to guide further policy formulation and budget research.MethodsThrough semi-structured group interviews and key informant interviews, five provinces and cities were investigated. Qualitative analysis was conducted based on stakeholder theory selected doctors and staff from Centers for Disease Control.ResultsThrough investigations in this study, problems like low purchasing price, insufficient purchasing volume, low drug supply efficiency, and monopoly producers were found. Through the analysis of roles and relationships among the major stakeholders in the second-line drug supply system, together with the motivation and resistance factors, it was found that all stakeholders have the motivation to solve the problem and face their dilemmas and obstacles at the same time.ConclusionsPatients with MDR-TB still have difficulties in obtaining medicines. The interests of various stakeholders need to be balanced to improve drug accessibility and affordability. It is recommended to take advantage of the country's centralized procurement, encourage the development and listing of new anti-tuberculosis drugs and generic drugs, and improve the supervision system to ensure the supply of drugs to benefit more patients with tuberculosis.

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Roen, A. O., D. Podlekareva, R. F. Miller, A. Mocroft, A. Panteleev, A. Skrahina, J. M. Miro, et al. "A new health care index predicts short term mortality for TB and HIV co-infected people." International Journal of Tuberculosis and Lung Disease 24, no. 9 (September 1, 2020): 956–62. http://dx.doi.org/10.5588/ijtld.19.0568.

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BACKGROUND: Using 2004–2007 TB:HIV Study data<x/> from Europe and Latin America, we previously generated a health care index (HCI) for TB and HIV co-infected people. With improvements in diagnostic and management practices, we have now updated the HCI with new data.METHODS: We evaluated nine aspects of health care in Cox proportional hazards models on time from TB diagnosis to death. Kaplan-Meier methods were used to estimate the probability of death by HCI quartile.RESULTS: Of 1396 eligible individuals (72% male, 59% from Eastern Europe), 269 died within 12 months. Use of rifamycin/isoniazid/pyrazinamide-based treatment (HR 0.67, 95% CI 0.50–0.89), TB drug susceptibility testing (DST) and number of active TB drugs (DST + <3 drugs (HR 1.09, 95% CI 0.80–1.48), DST + ≥3 drugs (HR 0.49, 95% CI 0.35–0.70) vs. no DST), recent HIV-RNA measurement (HR 0.64, 95% CI 0.50–0.82) and combination antiretroviral therapy use (HR 0.72, 95% CI 0.53–0.97) were associated with mortality. These factors contributed respectively 5, –1, 8, 5 and 4 to the HCI<x/>. Lower HCI was associated with an increased probability of death; 30% (95% CI 26–35) vs. 9% (95% CI 6–13) in the lowest vs. the highest quartile.<x/>CONCLUSION: We found five potentially modifiable health care components that were associated with mortality among TB-HIV positive individuals. Validation of our HCI in other TB cohorts could enhance our findings.

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Xu, Yuhui, Bowen Liang, Chengcheng Kong, and Zhaogang Sun. "Traditional Medicinal Plants as a Source of Antituberculosis Drugs: A System Review." BioMed Research International 2021 (September 8, 2021): 1–36. http://dx.doi.org/10.1155/2021/9910365.

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Medicinal plants are the chief components in the different oriental formulations in different traditional medical systems worldwide. As a thriving source of medicine, the medicinal plants with antituberculosis (TB) properties inspire the pharmacists to develop new drugs based on their active components or semimetabolites. In the present review, the anti-TB medicinal plants were screened from the scientific literatures, based on the botanical classification and the anti-TB activity. The obtained anti-TB medicinal plants were categorized into three different categories, viz., 159 plants critically examined with a total 335 isolated compounds, 131 plants with their crude extracts showing anti-TB activity, and 27 plants in literature with the prescribed formula by the traditional healers. Our systemic analysis on the medicinal plants can assist the discovery of novel and more efficacious anti-TB drugs.

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Santiago, M. R., A. M. C. Garfin, and V. M. Balanag. "Introduction of bedaquiline for the treatment of drug-resistant TB in the Philippines." International Journal of Tuberculosis and Lung Disease 24, no. 10 (October 1, 2020): 1063–66. http://dx.doi.org/10.5588/ijtld.20.0359.

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Treatment outcomes in patients with drug-resistant tuberculosis (DR-TB) remains unsatisfactory in the Philippines. To address this, we implemented the use of new anti-TB drugs and novel regimens. The Philippine National Tuberculosis Control Program (NTP) participated in the Bedaquiline (BDQ) Donation Program created by the US Agency for International Development and Janssen. Despite availability of donated medicine, there was a delay in the implementation of BDQ, both under operational research and programme conditions. The main challenges encountered were delayed approval by national and institutional ethics boards; limited experience of the NTP in the conduct of operational research into new drugs; and the lack of confidence of healthcare staff in the use of new and re-purposed anti-TB drugs. Technical assistance from partners and capacity building on clinical management of DR-TB and on pharmacovigilance among health workers were vital in overcoming these challenges. Over a 3-year period (from 2016–2018), 448 patients were initiated on BDQ-based regimens.

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Foo, Caroline Shi-Yan, Kevin Pethe, and Andréanne Lupien. "Oxidative Phosphorylation—an Update on a New, Essential Target Space for Drug Discovery in Mycobacterium tuberculosis." Applied Sciences 10, no. 7 (March 29, 2020): 2339. http://dx.doi.org/10.3390/app10072339.

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New drugs with new mechanisms of action are urgently required to tackle the global tuberculosis epidemic. Following the FDA-approval of the ATP synthase inhibitor bedaquiline (Sirturo®), energy metabolism has become the subject of intense focus as a novel pathway to exploit for tuberculosis drug development. This enthusiasm stems from the fact that oxidative phosphorylation (OxPhos) and the maintenance of the transmembrane electrochemical gradient are essential for the viability of replicating and non-replicating Mycobacterium tuberculosis (M. tb), the etiological agent of human tuberculosis (TB). Therefore, new drugs targeting this pathway have the potential to shorten TB treatment, which is one of the major goals of TB drug discovery. This review summarises the latest and key findings regarding the OxPhos pathway in M. tb and provides an overview of the inhibitors targeting various components. We also discuss the potential of new regimens containing these inhibitors, the flexibility of this pathway and, consequently, the complexity in targeting it. Lastly, we discuss opportunities and future directions of this drug target space.

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Kamal, Ahmed, Shaik Azeeza, M. Shaheer Malik, Ahmad Ali Shaik, and Maddamsetty V. Rao. "Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds." Journal of Pharmacy & Pharmaceutical Sciences 11, no. 2 (September 9, 2008): 56. http://dx.doi.org/10.18433/j36k5k.

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Development of new chemotherapeutic drugs is the need of the hour to improve tuberculosis control, particularly in the developing world. In the last fourty years no new compound has been brought to the market for the treatment of tuberculosis. However, in recent years there is an enhanced activity in the research and development of new drugs for TB. Some compounds are presently in clinical development, while others are being investigated pre-clinically in an attempt to explore new molecules for the target based treatment of TB. Simultaneously some new targets are being identified and validated for their practical usefulness. Structures based on thiolactomycin could have considerable potential in the development of target based anti-TB agents. The present review provides an overview of the drugs that are being clinically used and the compounds that are in advanced stages of clinical as well as preclinical studies. We have also attempted to highlight the efforts that are being made in the development of new molecules based on thiolactomycin as lead compound, including studies from this laboratory.

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Quispe, N., L. Asencios, C. Obregon, G. E. Velásquez, C. D. Mitnick, M. Lindeborg, H. Jave, and L. Solari. "The fourth national anti-tuberculosis drug resistance survey in Peru." International Journal of Tuberculosis and Lung Disease 24, no. 2 (February 1, 2020): 207–13. http://dx.doi.org/10.5588/ijtld.19.0186.

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BACKGROUND: Peru has one of the highest burdens of multidrug-resistant tuberculosis (MDR-TB), but universal drug susceptibility testing (DST) has not yet been achieved.OBJECTIVE: To estimate the proportion of drug resistance among smear-positive TB patients in Peru.DESIGN: From September 2014 to March 2015, we performed a national drug resistance survey of patients aged ≥15 years; TB was diagnosed based on sputum smear positivity. We performed DST at the National Reference Laboratory of the Peruvian National Institute of Health, Lima, Peru, using the proportion method in Middlebrook 7H10 agar for four first-line drugs and six second-line drugs, and the Wayne method for pyrazinamide.RESULTS: Of the 1908 new and 272 previously treated patients included in the analysis, 638 (29.3%) patients had resistance to at least one first-line drug. MDR-TB was diagnosed in 7.3% of new and 16.2% of previously treated patients (P < 0.001). There were five (0.2%) patients with extensively drug-resistant TB.CONCLUSION: MDR-TB has increased to 7.3% in new patients from 5.3% in the previous survey, indicating that resistance to anti-tuberculosis drugs is increasing in Peru. Ongoing community transmission of resistant strains highlights an urgent need for early diagnosis, optimised treatment and effective contact tracing of MDR-TB patients.

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Hutson, Stu. "Half-century-old TB drugs get a facelift in new cocktails." Nature Medicine 16, no. 12 (December 2010): 1346. http://dx.doi.org/10.1038/nm1210-1346b.

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Cook, Gregory M. "Energetics of mycobacteria: A fertile area for new anti-TB drugs." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1797 (July 2010): 111–12. http://dx.doi.org/10.1016/j.bbabio.2010.04.335.

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Defelipe, L., L. Radusky, C. Modenutti, E. Sosa, D. A. Fernández Do Porto, M. Marti, and A. Turjanski. "Open source Bioinformatics tools for the development of new TB drugs." International Journal of Infectious Diseases 73 (August 2018): 341. http://dx.doi.org/10.1016/j.ijid.2018.04.4188.

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Tesema, E., F. Wares, A. Bedru, C. Negeri, Y. Molla, D. Gemechu, A. Kassa, F. Tsegaye, and L. Taye. "Experiences of introducing new drugs for drug-resistant TB at the ALERT Hospital, Addis Ababa, Ethiopia, 2017–2019." Public Health Action 11, no. 2 (June 21, 2021): 50–52. http://dx.doi.org/10.5588/pha.20.0065.

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BACKGROUND: Drug-resistant TB (DR-TB) remains a major public health concern. DR-TB patient data from ALERT (All Africa Leprosy, Tuberculosis and Rehabilitation Training Centre) Hospital, Addis Ababa, Ethiopia, who received bedaquiline (BDQ) and/or delamanid (DLM) containing regimens were analysed.RESULTS: From 2017 to 2019, 51 DR-TB patients were enrolled. Of 33 patients, 31 (93.9%) had culture converted at 6 months. Of those with final outcomes, 77% (n = 10) were cured. Thirty (58.8%) developed adverse events, the most frequent of which were gastrointestinal disorders (70%), haematological disorders (16.7%) and QTc prolongation (16.7%). Twenty patients discontinued the offending drug permanently.CONCLUSION: With close monitoring, introduction of new DR-TB regimens brought good early results, which encouraged wider programmatic implementation in Ethiopia.

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Thanna, Sandeep, and Steven J. Sucheck. "Targeting the trehalose utilization pathways ofMycobacterium tuberculosis." MedChemComm 7, no. 1 (2016): 69–85. http://dx.doi.org/10.1039/c5md00376h.

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de Souza, Marcus Vinicius Nora, and Thais Cristina Mendonça Nogueira. "4H-1,3-Benzothiazin-4-one a Promising Class Against MDR/XDR-TB." Current Topics in Medicinal Chemistry 19, no. 8 (June 3, 2019): 567–78. http://dx.doi.org/10.2174/1568026619666190305130809.

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Nowadays, tuberculosis (TB) is an important global public health problem, being responsible for millions of TB-related deaths worldwide. Due to the increased number of cases and resistance of Mycobacterium tuberculosis to all drugs used for the treatment of this disease, we desperately need new drugs and strategies that could reduce treatment time with fewer side effects, reduced cost and highly active drugs against resistant strains and latent disease. Considering that, 4H-1,3-benzothiazin-4-one is a promising class of antimycobacterial agents in special against TB-resistant strains being the aim of this review the discussion of different aspects of this chemical class such as synthesis, mechanism of action, medicinal chemistry and combination with other drugs.

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Das, M., F. Mamnoon, H. Mansoor, A. C. Meneguim, P. Singh, I. Shah, S. Ravi, et al. "New TB drugs for the treatment of children and adolescents with rifampicin-resistant TB in Mumbai, India." International Journal of Tuberculosis and Lung Disease 24, no. 12 (December 1, 2020): 1265–71. http://dx.doi.org/10.5588/ijtld.20.0165.

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SETTING: Médecins Sans Frontières (MSF) clinic in Mumbai, India.OBJECTIVE: To determine the final treatment outcomes, culture conversion and adverse events (AEs) during treatment among children and adolescents (0–19 years) with rifampicin-resistant tuberculosis (RR-TB) who received ambulatory injectable-free treatment, including bedaquiline (BDQ) and/or delamanid (DLM) during September 2014–January 2020.DESIGN: This was a retrospective cohort study based on review of routinely collected programme data.RESULTS: Twenty-four patients were included; the median age was 15.5 years (min-max 3–19) and 15 (63%) were females. None were HIV-coinfected. All had fluoroquinolone resistance. Twelve received treatment, including BDQ and DLM, 11 received DLM and one BDQ. The median exposure to BDQ (n = 13) and DLM (n = 23) was 82 (IQR 80–93) and 82 (IQR 77–96) weeks, respectively. Seventeen (94%) patients with positive culture at baseline (n = 18) had negative culture during treatment; median time for culture-conversion was 7 weeks (IQR 5–11). Twenty-three (96%) had successful treatment outcomes: cured (n = 16) or completed treatment (n = 7); one died. Eleven (46%) had 17 episodes of AEs. Two of 12 serious AEs were associated with new drugs (QTcF >500 ms).CONCLUSION: Based on one of the largest global cohorts of children and adolescents to receive new TB drugs, this study has shown that injectable-free regimens containing BDQ and/or DLM on ambulatory basis were effective and well-tolerated among children and adolescents and should be made routinely accessible to these vulnerable groups.

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Rutta, E., C. Kambili, and Y. Mukadi. "The Bedaquiline Donation Program: progress and lessons learned after 4 years of implementation." International Journal of Tuberculosis and Lung Disease 24, no. 10 (October 1, 2020): 1039–45. http://dx.doi.org/10.5588/ijtld.20.0134.

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The Bedaquiline Donation Program was a global public-private partnership between the US Agency for International Development (USAID) and Janssen Therapeutics. The 4-year program was intended to accelerate access to bedaquiline (BDQ) by committing 30 000 treatment courses to more than eligible 100 countries. The program was designed to remove barriers by making the drug available through the Global Drug Facility (GDF); prepare TB programs to a changing drug-resistant TB (DR-TB) treatment landscape; improve quality of the entire DR-TB care paradigm; gather additional effectiveness and safety data in programmatic settings; and identify programmatic challenges associated with new TB drug introduction. By the end of the program (in April 2019), 80 countries had ordered 104 344 BDQ courses, of which 33 119 had been delivered (the rest were pending delivery). The introduction of new TB drugs offers hope to patients and an opportunity to transform DR-TB treatment with shorter, simpler and more tolerable regimens. The Bedaquiline Donation Program demonstrated that access to new drugs can be accelerated. Technical support to improve the overall quality of care is critical as are investments beyond the cost of the drug.

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Alzahabi, Khaled H., Omar Usmani, Theoni K. Georgiou, Mary P. Ryan, Brian D. Robertson, Teresa D. Tetley, and Alexandra E. Porter. "Approaches to treating tuberculosis by encapsulating metal ions and anti-mycobacterial drugs utilizing nano- and microparticle technologies." Emerging Topics in Life Sciences 4, no. 6 (December 14, 2020): 581–600. http://dx.doi.org/10.1042/etls20190154.

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Tuberculosis (TB) is caused by a bacterial infection that affects a number of human organs, primarily the lungs, but also the liver, spleen, and spine, causing key symptoms of fever, fatigue, and persistent cough, and if not treated properly, can be fatal. Every year, 10 million individuals become ill with active TB resulting with a mortality approximating 1.5 million. Current treatment guidelines recommend oral administration of a combination of first-line anti-TB drugs for at least 6 months. While efficacious under optimum conditions, ‘Directly Observed Therapy Short-course’ (DOTS) is not without problems. The long treatment time and poor pharmacokinetics, alongside drug side effects lead to poor patient compliance and has accelerated the emergence of multi-drug resistant (MDR) organisms. All this, combined with the limited number of newly discovered TB drugs to treat MDR-TB and shorten standard therapy time, has highlighted the need for new targeted drug delivery systems. In this respect, there has been recent focus on micro- and nano-particle technologies to prepare organic or/and metal particles loaded with TB drugs to enhance their efficacy by targeted delivery via the inhaled route. In this review, we provide a brief overview of the current epidemiology of TB, and risk factors for progression of latent stage tuberculosis (LTBI) to the active TB. We identify current TB treatment regimens, newly discovered TB drugs, and identify studies that have used micro- or nano-particles technologies to design a reliable inhalation drug delivery system to treat TB more effectively.

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Macalino, Stephani Joy Y., Junie B. Billones, Voltaire G. Organo, and Maria Constancia O. Carrillo. "In Silico Strategies in Tuberculosis Drug Discovery." Molecules 25, no. 3 (February 4, 2020): 665. http://dx.doi.org/10.3390/molecules25030665.

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Tuberculosis (TB) remains a serious threat to global public health, responsible for an estimated 1.5 million mortalities in 2018. While there are available therapeutics for this infection, slow-acting drugs, poor patient compliance, drug toxicity, and drug resistance require the discovery of novel TB drugs. Discovering new and more potent antibiotics that target novel TB protein targets is an attractive strategy towards controlling the global TB epidemic. In silico strategies can be applied at multiple stages of the drug discovery paradigm to expedite the identification of novel anti-TB therapeutics. In this paper, we discuss the current TB treatment, emergence of drug resistance, and the effective application of computational tools to the different stages of TB drug discovery when combined with traditional biochemical methods. We will also highlight the strengths and points of improvement in in silico TB drug discovery research, as well as possible future perspectives in this field.

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Dooley, Kelly E., Peter S. Kim, Sharon D. Williams, and Richard Hafner. "TB and HIV Therapeutics: Pharmacology Research Priorities." AIDS Research and Treatment 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/874083.

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An unprecedented number of investigational drugs are in the development pipeline for the treatment of tuberculosis. Among patients with tuberculosis, co-infection with HIV is common, and concurrent treatment of tuberculosis and HIV is now the standard of care. To ensure that combinations of anti-tuberculosis drugs and antiretrovirals are safe and are tested at doses most likely to be effective, selected pharmacokinetic studies based on knowledge of their metabolic pathways and their capacity to induce or inhibit metabolizing enzymes of companion drugs must be conducted. Drug interaction studies should be followed up by evaluations in larger populations to evaluate safety and pharmacodynamics more fully. Involving patients with HIV in trials of TB drugs early in development enhances the knowledge gained from the trials and will ensure that promising new tuberculosis treatments are available to patients with HIV as early as possible. In this review, we summarize current and planned pharmacokinetic and drug interaction studies involving investigational and licensed tuberculosis drugs and antiretrovirals and suggest priorities for tuberculosis-HIV pharmacokinetic, pharmacodynamic, and drug-drug interaction studies for the future. Priority studies for children and pregnant women with HIV and tuberculosis co-infection are briefly discussed.

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Ikeda, Robin M., Guthrie S. Birkhead, George T. DiFerdinando, Donald L. Bornstein, Samuel W. Dooley, George P. Kubica, and Dale L. Morse. "Nosocomial Tuberculosis: An Outbreak of a Strain Resistant to Seven Drugs." Infection Control & Hospital Epidemiology 16, no. 3 (March 1995): 152–59. http://dx.doi.org/10.1017/s0195941700007293.

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AbstractObjective:To evaluate nosocomial transmission of multidrug-resistant (MDR) tuberculosis (TB).Design:Outbreak investigation: review of infection control practices and skin test results of healthcare workers (HCWs); medical records of hospitalized TB patients and mycobacteriology reports; submission of specimens for restriction fragment length polymorphism (RFLP) typing; and an assessment of the air-handling system.Setting:A teaching hospital in upstate New York.Results:Skin-test conversions occurred among 46 (6.6%) of 696 HCWs tested from August through October 1991. Rates were highest on two units (29% and 20%); HCWs primarily assigned to these units had a higher risk for conversion compared with HCWs tested following previous incidents of exposure to TB (relative risk [RR] = 53.4, 95% confidence interval [CI95] =6.9 to 411.1; and RR=37.4, CI95= 5.0 to 277.3, respectively). The likely source patient was the only TB patient hospitalized on both units during the probable exposure period. This patient appeared clinically infectious, was associated with a higher risk of conversion among HCWs providing direct care (RR = 2.37; CI95 = 1.05 to 5.34), and was a prison inmate with TB resistant to seven antituberculosis agents. The MDR-TB strain isolated from this patient also was isolated from other inmate and noninmate patients, and a prison correctional officer exposed in the hospital. Mycobacterium tuberculosis isolates from all of these patients had matching RFLP patterns. Infection control practices closely followed established guidelines; however, several rooms housing TB patients had marginal negative pressure with variable numbers of air changes per hour, and directional airflow was disrupted easily.Conclusions:These data strongly suggest nosocomial transmission of MDR-TB to HCWs, patients, and a prison correctional officer working in the hospital. Factors contributing to transmission apparently included prolonged infectiousness of the likely source patient and inadequate environmental controls. Continued urgent attention to TB infection control is needed.

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Guglielmetti, L., J. Jaffré, C. Bernard, F. Brossier, N. El Helali, K. Chadelat, G. Thouvenin, et al. "Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium." International Journal of Tuberculosis and Lung Disease 23, no. 10 (October 1, 2019): 1050–54. http://dx.doi.org/10.5588/ijtld.18.0779.

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SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

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Ndjeka, N., J. Hughes, A. Reuter, F. Conradie, M. Enwerem, H. Ferreira, N. Ismail, et al. "Implementing novel regimens for drug-resistant TB in South Africa: what can the world learn?" International Journal of Tuberculosis and Lung Disease 24, no. 10 (October 1, 2020): 1073–80. http://dx.doi.org/10.5588/ijtld.20.0174.

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Worldwide uptake of new drugs in the treatment of rifampicin-resistant tuberculosis (RR-TB) has been extremely low. In June 2018, ahead of the release of the updated WHO guidelines for the management of RR-TB, South Africa announced that bedaquiline (BDQ) would be provided to virtually all RR-TB patients on shorter or longer regimens. South Africa has been the global leader in accessing BDQ for patients with RR-TB, who now represent 60% of the global BDQ cohort. The use of BDQ within a shorter modified regimen has generated the programmatic data underpinning the most recent change in WHO guidelines endorsing a shorter, injectable-free regimen. Progressive policies on access to new drugs have resulted in improved favourable outcomes and a reduction in mortality among RR-TB patients in South Africa. This supported global policy change. The strategies underpinning these bold actions include close collaboration between the South African National TB Programme and partners, introduction of new TB diagnostic tools in closely monitored conditions and the use of locally generated programmatic evidence to inform country policy changes. In this paper, we summarise a decade´s work that led to the bold decision to use a modified, short, injectable-free regimen with BDQ and linezolid under carefully monitored programmatic conditions.

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Nikonenko, Boris V., Marina Protopopova, Rowena Samala, Leo Einck, and Carol A. Nacy. "Drug Therapy of Experimental Tuberculosis (TB): Improved Outcome by Combining SQ109, a New Diamine Antibiotic, with Existing TB Drugs." Antimicrobial Agents and Chemotherapy 51, no. 4 (January 22, 2007): 1563–65. http://dx.doi.org/10.1128/aac.01326-06.

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ABSTRACT Substitution of the new diamine antibiotic SQ109 for ethambutol in a mouse model of chronic tuberculosis (TB) improved efficacy of combination drug therapy with first-line TB drugs rifampin and isoniazid, with or without pyrazinamide: at 8 weeks, lung bacteria were 1.5 log10 lower in SQ109-containing regimens.

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Palmero, Domingo, and Viviana Ritacco. "Clinical Management of Drug-Resistant Tuberculosis in Resource Constrained Settings." Clinical Medicine Insights: Therapeutics 5 (January 2013): CMT.S6560. http://dx.doi.org/10.4137/cmt.s6560.

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Drug-resistant forms of tuberculosis (TB), particularly multi- and extensively drug-resistant TB, represent an important obstacle to global control of the disease. Recently, new drugs, repurposed drugs, and new drug combinations have been evaluated, with a number showing promise for the treatment of drug-resistant TB. Additionally, a range of methods for accelerating mycobacterial culture, identification, and drug susceptibility testing have been developed, and several in-house and commercial genotyping methods for speeding drug resistance detection have become available. Despite these significant achievements in drug development and diagnostics, drug-resistant TB continues to be difficult to diagnose and treat. Significant international efforts are still needed, especially in the field of clinical and operational research, to translate these encouraging developments into effective patient cure and make them readily available to resource-constrained settings, where they are most needed.

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Journal articles on the topic 'New TB drugs'

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