Novel Approaches for the Treatment of Drug-Resistant Tuberculosis (original) (raw)

New tuberculosis therapeutics : A growing pipeline

The Journal of Infectious Diseases, 2007

Novel chemotherapeutic drugs are needed to improve tuberculosis (TB) control, especially in the developing world. Given the magnitude of the problem and the resources available in countries that have the highest burden of disease, the present standards of care for the treatment of drug-susceptible TB, drug-resistant TB, TB/human immunodeficiency virus (HIV) coinfection, and latent TB infection are all unsatisfactory. Because no truly novel compounds for the treatment of TB have been discovered in the past 40 years, the recent enhanced activity in the research and development of new TB drugs is extremely encouraging. Seven compounds are presently in clinical development specifically for the treatment of TB. Other known antibiotic compound families are being investigated preclinically, in an attempt to identify new antimicrobial drugs with specific antituberculous activity. In addition, novel targets have been identified and are the subject of efforts to validate their potential usefulness in the treatment of TB.

Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment

Pharmaceutics, 2021

Control of Mycobacterium tuberculosis infection continues to be an issue, particularly in countries with a high tuberculosis (TB) burden in the tropical and sub-tropical regions. The effort to reduce the catastrophic cost of TB with the WHO’s End TB Strategy in 2035 is still obstructed by the emergence of drug-resistant TB (DR-TB) cases as result of various mutations of the MTB strain. In the approach to combat DR-TB, several potential antitubercular agents were discovered as inhibitors for various existing and novel targets. Host-directed therapy and immunotherapy also gained attention as the drug-susceptibility level of the pathogen can be reduced due to the pathogen’s evolutionary dynamics. This review is focused on the current progress and challenges in DR-TB treatment. We briefly summarized antitubercular compounds that are under development and trials for both DR-TB drug candidates and host-directed therapy. We also highlighted several problems in DR-TB diagnosis, the treatmen...

Drug-resistant tuberculosis: emerging treatment options

Clinical Pharmacology: Advances and Applications, 2011

Multidrug-resistant tuberculosis has emerged worldwide, with an increasing incidence due to failure of implementation of apparently effective first-line antituberculous therapy as well as primary infection with drug-resistant strains. Failure of current therapy is attributed to a long duration of treatment leading to nonadherence and irregular therapy, lack of patient education about the disease, poverty, irregular supply by care providers, drug-drug interactions in patients coinfected with human immunodeficiency virus (HIV), inadequate regulations causing market overlap and irresponsible drug usage in the private sector, and lack of research, with no addition of new drugs in the last four decades. Present standards of care for the treatment of drugsusceptible tuberculosis, multidrug-resistant tuberculosis, tuberculosis-HIV coinfection, and latent tuberculosis infection are all unsatisfactory. Since 2000, the World Health Organization (WHO) has focused on drug development for tuberculosis, as well as research in all relevant aspects to discover new regimens by 2015 and to eliminate tuberculosis as a public health concern by 2050. As a result, some 20 promising compounds from 14 groups of drugs have been discovered. Twelve candidates from eight classes are currently being evaluated in clinical trials. Ongoing research should prioritize identification of novel targets and newer application of existing drugs, discovery of multitargeted drugs from natural compounds, strengthening host factors by immunopotentiation with herbal immunomodulators, as well as protective vaccines before and after exposure, consideration of surgical measures when indicated, development of tools for rapid diagnosis, early identification of resistant strains, and markers for adequacy of treatment and an integrative approach to fulfill WHO goals. However, regulatory control over the drug market, as well as public-private partnership to use health program facilities to track patients and ensure completion of adequate therapy will be necessary to exploit fully the potential of the newer regimens to eliminate tuberculosis.

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...

Current development and future prospects in chemotherapy of tuberculosis

Respirology, 2010

Novel chemotherapeutic drugs are needed to improve tuberculosis (TB) control, especially in the developing world. Given the magnitude of the problem and the resources available in countries that have the highest burden of disease, the present standards of care for the treatment of drug-susceptible TB, drug-resistant TB, TB/human immunodeficiency virus (HIV) coinfection, and latent TB infection are all unsatisfactory. Because no truly novel compounds for the treatment of TB have been discovered in the past 40 years, the recent enhanced activity in the research and development of new TB drugs is extremely encouraging. Seven compounds are presently in clinical development specifically for the treatment of TB. Other known antibiotic compound families are being investigated preclinically, in an attempt to identify new antimicrobial drugs with specific antituberculous activity. In addition, novel targets have been identified and are the subject of efforts to validate their potential usefulness in the treatment of TB. q32 q33 q34 q35 q36 q37 q38

Novel Compounds and Drugs and Recent Patents in Treating Multidrug- Resistant and Extensively Drug-Resistant Tuberculosis

Recent Patents on Anti-Infective Drug Discovery, 2012

A number of recent studies revealed that successful treatment of the patients with MDR/XDR-TB was not achieved due to high resistant rates to many second-line drugs such as kanamycin and prothionamide including poor adherence of the lengthy treatment. Many new drugs and compounds such as benzothiazinones, meropenem, PA-824, isoflavonoids, rhein, PNU-100480, TMC207, SQ109, OPC-67683, AZD5847, and linezolid are currently in development pipeline. According to very few patents in new compounds and drugs against MDR/XDR-Mycobacterium tuberculosis bacilli have been currently introduced, so inventors must be encouraged to contribute to this area worldwide.

New drugs against tuberculosis: problems, progress, and evaluation of agents in clinical development

Antimicrobial Agents and Chemotherapy, 2009

One-third of the world population is infected with Mycobac- terium tuberculosis (MTB) and hence at risk of developing active tuberculosis (TB). Each year, 8.8 million patients are newly diagnosed with active TB and 1.6 million patients die of TB. The rapid spread of the human immunodeficiency virus (HIV) has fueled the TB epidemic, especially in sub-Saharan Africa, where 28% of