The challenge of the new tuberculosis drugs (original) (raw)

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.

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...

New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians

Respiration

Although tuberculosis (TB) is preventable and curable, the lengthy treatment (generally 6 months), poor patient adherence, high inter-individual variability in pharmacokinetics (PK), emergence of drug resistance, presence of comorbidities, and adverse drug reactions complicate TB therapy and drive the need for new drugs and/or regimens. Hence, new compounds are being developed, available drugs are repurposed, and the dosing of existing drugs is optimized, resulting in the largest drug development portfolio in TB history. This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid. The review covers drug development history, preclinical data, PK, and current clinical development.

Drugs in Development for Tuberculosis

Drugs, 2010

Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain. These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues; rising and disturbing rates of multidrug-and extensively drugresistant TB; the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co-epidemic. Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first-and second-line TB drugs. Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient age.

New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis

Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia, 2018

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 ...

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