Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment of the Challenge: Works

Addressing the Threat of Drug-Resistant Tuberculosis: A Realistic Assessment to assess patients' susceptibility to the second-line drugs used to treat MDR TB. to combat TB to share information, develop an understanding of the challenges, .. staff, and investigators who can work to current global registration standards.
Table of contents

To achieve these goals, we may need to change the way partnerships between basic research scientists and biotechnology companies are structured, to ensure that promising new diagnostics progress into clinical development and to the marketplace within a reasonable amount of time and at a reasonable cost. In addition, we must proactively identify and embrace innovation in diagnostics research. Diagnostic advances suitable for adaptation to TB are likely to emerge from platform technologies supported for other infectious diseases, such as those being developed by the biodefense and emerging infectious diseases program at the NIAID.

Creating diagnostic tools that are suitable for field use in sites with limited infrastructure will constitute an additional challenge. The most critical need for patients with drug-resistant TB is access to new drugs. Several new therapies are in clinical trials, some of which are the direct result of NIAID research efforts and partnerships [ 21 ] table 1. Unfortunately, new TB therapeutics are not expected to be widely available in the immediate future. In the interim, it has been recognized that even the current first- and second-line therapies for TB are likely not fully optimized and need to be reexamined to determine whether adequate drug levels are being achieved in patients with advanced disease, in children, in those receiving antiretroviral therapies, and in those with other comorbidities [ 22—24 ].

Furthermore, FDA-approved antibiotics not currently used for treatment of TB should be tested clinically to determine whether they can contribute to treatment approaches for drug-resistant and drug-susceptible TB; if this is the case, additional drugs with anti— M. Programs for the genetic sequencing of representative M.

Multi-Drug-Resistant Tuberculosis drug on trial

Answers to these research questions will not only improve our understanding of the pathogenesis of TB and provide additional drug targets and potential diagnostic and immunological markers but, hopefully, will also help to prevent development of drug resistance in the future. Immunocompromised individuals, including those with advanced HIV infection, are at greatly increased risk of developing active TB caused by either a new M.


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Although management of drug-susceptible TB in HIV-coinfected patients is very complex, and solid data to guide treatment, particularly in the presence of additional comorbidities, remain inadequate, we know even less about the treatment of drug-resistant TB in these patients. For second-line therapies, many basic facts regarding drug-drug interactions, toxicities, achievable drug levels, and drug metabolism remain to be determined in HIV-coinfected individuals to ensure that the treatment options currently available are applied optimally and provide acceptable efficacy.

TB prevention and adjuncts to therapy. The largest potential impact on TB control and the development of drug resistance would come from effective vaccines to prevent all forms of TB. Development of new vaccines and vaccination strategies has been stymied by a lack of understanding of the nature and mechanisms of immune protection that would have to be elicited by an effective vaccine. Clinical studies of new vaccine candidates are hampered by a limited understanding of surrogate markers of infection and correlates of immune protection. Vaccine development will continue to be empirical until phase 3 clinical trials have been completed to validate available markers.

Combining chemotherapy with various vaccines has the theoretical potential to contribute to the increased effectiveness of drug regimens, to provide alternative strategies for limiting the duration of infectiousness of patients with TB, and to contribute to chemopreventive strategies for latent infection with MDR M.

To ensure that diagnostics, drugs, and vaccines can be developed in an effective manner, already-strong collaborations among US and international partners need to be expanded to include a clear articulation of the role and practical commitment of each entity in filling specific gaps along the product-development continuum from basic science to late-stage clinical trials.

Only a concerted global effort will successfully counteract the remarkable resilience of M. Beverly Alston, Clifton E. Gray Handley, Steven M. Touchette, and Laura E.


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View large Download slide. Centers for Disease Control and Prevention.

Tuberculosis (TB)

Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, — Transmission of drug-resistant tuberculosis among treated patients in Shanghai, China. National Institute of Allergy and Infectious Diseases.

WHO | Drug- and multidrug-resistant tuberculosis (MDR-TB) - Frequently asked questions

Current status of some anti-tuberculosis drugs and the development of new anti-tuberculosis agents with special reference to their in vitro and in vivo antimicrobial activities. The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis. Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. Tuberculosis and human immunodeficiency virus co-infection in children: Potential conflicts of interest: Email alerts New issue alert.

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Drug- and multidrug-resistant tuberculosis (MDR-TB) - Frequently asked questions

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The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. Tuberculosis is one of the leading causes of death in the world today, with 4, people dying from the disease every day. Many cases of TB can be cured by available antibiotics, but some TB is resistant to multiple drugs--a major and growing threat worldwide. The session brought together a wide range of international experts to discuss what is known and not known about this growing threat, and to explore possible solutions.

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