Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis

Institute of Tropical Medicine, Nationalestraat 155, Antwerp, Belgium.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 11.99). 05/2010; 182(5):684-92. DOI: 10.1164/rccm.201001-0077OC
Source: PubMed

ABSTRACT Based on expert opinion, the global guidelines for management of multidrug-resistant tuberculosis impose lengthy and often poorly tolerated treatments.
This observational study evaluates the effectiveness of standardized regimens for patients with proven multidrug-resistant tuberculosis previously untreated with second-line drugs in low-income countries.
Consenting patients were sequentially assigned to one of six standardized treatment regimens. Subsequent cohorts were treated with regimens adapted according to results in prior cohorts. The study was designed to minimize failure and default while reducing total treatment duration without increasing relapse frequency.
We report the treatment outcome of all patients with laboratory-confirmed, multidrug-resistant tuberculosis enrolled from May 1997 to December 2007. The most effective treatment regimen required a minimum of 9 months of treatment with gatifloxacin, clofazimine, ethambutol, and pyrazinamide throughout the treatment period supplemented by prothionamide, kanamycin, and high-dose isoniazid during an intensive phase of a minimum of 4 months, giving a relapse-free cure of 87.9% (95% confidence interval, 82.7-91.6) among 206 patients. Major adverse drug reactions were infrequent and manageable. Compared with the 221 patients treated with regimens based on ofloxacin and commonly prothionamide throughout, the hazard ratio of any adverse outcome was 0.39 (95% confidence interval, 0.26-0.59).
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.

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Available from: Md A Hamid Salim, Jul 14, 2015
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    • "During this delay, patients with drug-resistant TB may continue failing empirical regimens, leading to community transmission and resistance amplification (Farmer et al. 1998; Furin et al. 2000). Although successful treatment of MDR-TB has been demonstrated in resource-poor settings (Mitnick et al. 2003; Van Deun et al. 2010), studies have shown mortality rates of patients awaiting DST results and ultimately diagnosed with MDR-TB to range from 12 to 50% (Singla et al. 2009). Harries et al. (2004) published a report from Malawi showing that despite implementation of a new bus transport system for re-treatment specimens, 60% of cases resulted in a sample not being received by the central laboratory. "
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    ABSTRACT: Objective Kenya, like many resource-constrained countries, has a single mycobacterial laboratory, centrally located in Nairobi, with capacity for drug-susceptibility testing (DST) – the gold standard in diagnosing drug-resistant tuberculosis. We describe and evaluate a novel operational design that attempts to overcome diagnostic delivery barriers. Methods Review of the public DST programme identified several barriers limiting access: lack of programme awareness amongst physicians, limited supplies, unreliable transport and no specimen tracking methods. Staff visited 19 clinic sites in western Kenya and trained healthcare providers in regard to the novel diagnostics model. Provincial laboratory registries were reviewed to assess utilization of DST services prior to and after programme modification. Results Onsite training consisted of the inclusion criteria for re-treatment patients – the high-priority group for DST. Additionally, infrastructural support established a stable supply chain. An existing transport system was adapted to deliver sputum specimens. Task shifting created an accession and tracking system of specimens. During the 24 months post-implementation, the number of re-treatment specimens from the catchment area increased from 9.1 to 23.5 specimens per month. In comparing annual data pre- and post-implementation, the proportion of re-treatment cases receiving DST increased from 24.7% (n = 403) to 32.5% (n = 574) (P < 0.001), and the number of multidrug-resistant (MDR) TB cases increased from 5 to 10 cases. Conclusion The delivery model significantly increased the proportion of re-treatment cases receiving DST. Barriers to accessing the national MDR-TB surveillance programme can be overcome through an operational model based on pragmatic use of existing services from multiple partners.
    Tropical Medicine & International Health 12/2011; 17(3):374-9. DOI:10.1111/j.1365-3156.2011.02933.x · 2.30 Impact Factor
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    • "Le médicament injectable peut être supprimé après six mois de traitement ou quatre mois après la négativation des cultures. À côté des recommandations décrites ci-dessus, une étude comparée de plusieurs régimes thérapeutiques conduite au Bangladesh entre 1997 et 2007 a montré qu'il était possible d'obtenir la guérison de 87,9 % des cas de MDR- TB par un régime de neuf mois associant l'éthambutol, le pyrazinamide, la gatifloxacine et la clofazimine, complétés par la kanamycine, l'isoniazide à haute dose et le prothionamide pendant les quatre premiers mois [27]). Outre sa brièveté, un tel régime thérapeutique a l'avantage de coûter moins cher que les traitements proposés par l'OMS. "
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    ABSTRACT: Multidrug resistant tuberculosis (MDR-TB) has spread to most regions of the world and represents a serious threat to the success of the struggle against tuberculosis. It can result from errors in management that favour the selection of drug resistant organisms and can in the worst case lead to the development of extremely resistant organisms (XDR-TB) which are practically untreatable. The current strategies for combating this problem are, on the one hand, the rapid identification and tracking of resistant strains using molecular genetic techniques and, on the other hand, careful drug management in individual cases using second line agents. At the level of public health, the most important measures are those which prevent or correct the processes which can drive the creation of new cases of MDR-TB. This can have implications for the modification and development of national strategies. The future of the fight against tuberculosis depends in part on the success of strategies to combat the development and spread of MDR-TB.
    Revue des Maladies Respiratoires 10/2011; DOI:10.1016/j.rmr.2010.10.040 · 0.49 Impact Factor
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