Short, Highly Effective, and Inexpensive Standardized Treatment of Multidrug-resistant Tuberculosis

Abstract

Serial regimen formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with first-line treatment. Confirmatory formal trials in populations with high levels of human immunodeficiency virus coinfection and in populations with a higher initial prevalence of resistance to second-line drugs are required.

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…[42][43][44] The "Bangladesh'' shorter standardized regimen, achieved a relapse-free cure of 87.9% among 206 patients, this regimen achieved < 1% failure and 90% relapse-free cure. 45 Moreover, an update of this study has shown that 84.4% of the 515 patients had a bacteriologically favourable outcome. 40 The only difference between the Bangladesh regimen and the WHO shorter regimen is the substitution of gatifloxacin for moxifloxacin.…”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…Nevertheless, drawbacks of significant toxicity and pill burden, poor adherence, and 6-8 months of painful injections with second-line injectable drugs remain. Also in 2016, WHO has recommended a standardised shorter MDR tuberculosis treatment regimen that has been used with second-line drug treatment-naïve patients with MDR tuberculosis in Bangladesh, 277 Niger, 278 and Cameroon. 279 The shorter MDR tuberculosis regimen (9-12 months) is successful in approximately 90% of cases, and includes three drugs (kanamycin, prothionamide, and high-dose isoniazid) for 4-6 months, with additional drugs (moxifloxacin, clofazimine, pyrazinamide, and ethambutol) …”

“…356 Clofazimine is also considered a key component of a short-course regimen (ie, 9-12 months) recently endorsed by WHO for treatment of MDR tuberculosis after several observational cohorts reported good treatment success. [277][278][279] Clofazimine is highly lipophilic, it has a very large volume of distribution, and has a terminal half-life of 70 days. The drug becomes highly concentrated in fat, organs, and skin with long-term use.…”

Assessment of Clofazimine Activity in a Second-Line Regimen for Tuberculosis in Mice

“…The unfortunate development of multidrug-and extensively drug-resistant tuberculosis has kindled a worldwide push for the development of new therapy options for this disease, including a renewed interest in clofazimine (5). Although several groups have characterized clofazimine activity for in vitro and animal models of tuberculosis (6), a seminal publication by van Deun and colleagues in 2010 reported for the first time that a 9-month drug regimen including gatifloxacin, ethambutol, pyrazinamide, and clofazimine throughout plus a 4-month initial supplement of kanamycin, prothionamide, and a high dose of isoniazid achieved a relapse-free cure of 87.9% (95% confidence interval [CI], 82.7-91.6) among 206 patients in Bangladesh (7). Such a rate is higher than the 62% (95% CI, 57-67%) rate of successful outcomes reported in a recent systematic review of multidrug-resistant tuberculosis treatment (8), and it is also better than the 61% (95% CI, 53-69%) efficacy of the World Health Organization (WHO)-recommended two year-long retreatment regimen (9,10).…”