Evaluation of Rifapentine in Long-Term Treatment Regimens for Tuberculosis in Mice

ABSTRACT Besides direct bactericidal activity, long-term effectiveness is one of the most important features to consider when developing new drugs for chemotherapy. In this study, we evaluated the ability of rifapentine (RFP), in monotherapy and combination therapy, to completely eradicate a Mycobacterium tuberculosis infection and to prevent relapse posttreatment in a Swiss mouse model. The combination of RFP, isoniazid (INH), and pyrazinamide (PZA) administered daily resulted in an apparent clearance of M. tuberculosis organisms in the lungs and spleens of infected mice after 10 weeks of treatment. However, 3 months after the cessation of therapy, bacterial regrowth occurred in mice treated for a 12-week period, indicating a relapse of infection. In intermittent treatment regimens of RFP in combination with INH and PZA, sterilization was achieved when mice were treated two to five times per week for 9 weeks. Bacterial growth was still observed in the once-weekly treatment group. Our results show that mouse models can predict important parameters for new drugs. We stress the necessity for long-term posttreatment observation in animal models for the routine evaluation of new drugs for antituberculosis chemotherapy.

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Evaluation of Rifalazil in Long-Term Treatment Regimens for Tuberculosis in Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.6.1458-1462.2000 ◽

2000 ◽

Vol 44 (6) ◽

pp. 1458-1462 ◽

Cited By ~ 12

Author(s):

Carolyn M. Shoen ◽

Sharon E. Chase ◽

Michelle S. DeStefano ◽

Tami S. Harpster ◽

Alex J. Chmielewski ◽

...

Keyword(s):

Treatment Duration ◽

Treatment Time ◽

Term Treatment ◽

Treatment Regimens ◽

Short Course ◽

Long Term Treatment ◽

Nonculturable State ◽

Time Required ◽

Observation Period

ABSTRACT Previous experiments with rifalazil (RLZ) (also known as KRM-1648) in combination with isoniazid (INH) demonstrated its potential for short-course treatment of Mycobacterium tuberculosisinfection. In this study we investigated the minimum RLZ-INH treatment time required to eradicate M. tuberculosis in a murine model. RLZ-INH treatment for 6 weeks or longer led to a nonculturable state. Groups of mice treated in parallel were killed following an observation period to evaluate regrowth. RLZ-INH treatment for a minimum of 10 weeks was necessary to maintain a nonculturable state through the observation period. Pyrazinamide (PZA) was added to this regimen to determine whether the treatment duration could be further reduced. In this model, the addition of PZA did not shorten the duration of RLZ-INH treatment required to eradicate M. tuberculosis from mice. The addition of PZA reduced the number of mice in which regrowth occurred, although the reduction was not statistically significant.

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Vitiligo treatment algorithm

Russian Journal of Skin and Venereal Diseases ◽

10.18821/1560-9588-2016-19-3-167-169 ◽

2016 ◽

Vol 19 (3) ◽

pp. 167-169

Author(s):

Konstantin M. Lomonosov ◽

L. G Gereykhanova

Keyword(s):

Treatment Strategy ◽

Treatment Algorithm ◽

Previous Treatment ◽

Term Treatment ◽

Early Termination ◽

Treatment Regimens ◽

Long Term Treatment

The treatment strategy ofpatients with vitiligo, including the identification of motivation for long-term treatment and informing patients to avoid false expectations as causes of dissatisfaction and early termination of the therapeutic course are described. The algorithm for the treatment of vitiligo consists of five successive stages. Each of them is sequentially applied with no previous treatment regimens efficiency or its maximum possible effect achievement. The use of the described treatment algorithm allows us to achieve in 70-80% of cases a marked repigmentation of vitiligo and to ensure long-term and often life-long remission of the disease.

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Bonanza of New Treatment Regimens for Multiple Myeloma: What Is Right for My Patient?

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2020.5042 ◽

2020 ◽

Vol 18 (12.5) ◽

pp. 1773-1776

Author(s):

Shaji K. Kumar

Keyword(s):

Multiple Myeloma ◽

Chronic Disease ◽

Treatment Strategy ◽

Term Treatment ◽

New Agents ◽

Treatment Regimens ◽

Recent Advances ◽

Long Term Treatment ◽

New Treatment

Although recent advances in the treatment of multiple myeloma have improved survival, it remains a chronic disease that requires a long-term treatment strategy. The key to achieving the best outcomes for patients is delivering the best “package” of treatment at a given stage. This means using optimal combinations that maximize benefit based on what patients have received previously and minimize treatment-related toxicity. Sequencing of regimens also plays an important role. As new agents and new classes of drugs continue to be approved for multiple myeloma, future strategies will use more individualized approaches to treatment.

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Efficacy of Long Term Treatment Regimens on Cyclic Vomiting Syndrome in Adults

The American Journal of Gastroenterology ◽

10.14309/00000434-200809001-01188 ◽

2008 ◽

Vol 103 ◽

pp. S464

Author(s):

Reza Hejazi ◽

Teri Lavenbarg ◽

Savio Reddymasu ◽

Pernilla Foran ◽

Richard McCallum

Keyword(s):

Term Treatment ◽

Cyclic Vomiting Syndrome ◽

Treatment Regimens ◽

Long Term Treatment ◽

Cyclic Vomiting

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Anti-Human Immunodeficiency Virus Drug Combination Strategies

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029800900301 ◽

1998 ◽

Vol 9 (3) ◽

pp. 187-203 ◽

Cited By ~ 79

Author(s):

A-M Vandamme ◽

K Van Vaerenbergh ◽

E De Clercq

Keyword(s):

Human Immunodeficiency Virus ◽

Drug Resistance ◽

Salvage Therapy ◽

Highly Active Antiretroviral Therapy ◽

Term Treatment ◽

New Drugs ◽

Resistance Testing ◽

Long Term Treatment ◽

Immunodeficiency Virus

It is now generally accepted that mono- and bitherapy for human immunodeficiency virus type 1 (HIV-1) infection are only transiently efficient mainly due to virus drug resistance. To obtain a sustained benefit from antiviral therapy, current guidelines recommend at least triple-drug combinations, or the so-called highly active antiretroviral therapy (HAART). In some patients, HAART can be problematic, either because it is difficult to remain compliant or because previous suboptimum therapies have limited the choice of drugs. For compliant drug-naive patients, HAART should be able to offer long-term virus suppression, when changing from first- to second- to third-line HAART at drug failure. Long-term treatment might ultimately result in multi-drug resistant virus leaving few options for salvage therapy. HIV drug resistance testing to guide this salvage therapy and the development of new drugs to allow new options will therefore remain priorities in anti-HIV drug research.

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