The Journal of Association of Chest Physicians

EDITORIAL
Year
: 2017  |  Volume : 5  |  Issue : 2  |  Page : 65--66

The shorter regimen for MDR TB: Myth or reality


Kaushik Saha 
 Department of Pulmonary Medicine, Burdwan Medical College, Burdwan, West Bengal, India

Correspondence Address:
Kaushik Saha
Rabindra Pally, 1st Lane, Nimta, Kolkata 700 049, West Bengal
India




How to cite this article:
Saha K. The shorter regimen for MDR TB: Myth or reality.J Assoc Chest Physicians 2017;5:65-66


How to cite this URL:
Saha K. The shorter regimen for MDR TB: Myth or reality. J Assoc Chest Physicians [serial online] 2017 [cited 2017 Dec 15 ];5:65-66
Available from: http://www.jacpjournal.org/text.asp?2017/5/2/65/209308


Full Text

Tuberculosis (TB) is one of the major global health problems for decades, and with emergence of drug-resistant TB it became a public health crisis. There are about 580,000 new cases of rifampicin-resistant (RR) or multidrug resistant (MDR) TB occurring every year globally.[1] Conventional regimen for treating MDR TB is continued for at least 20 months.[2] Due to this long duration of treatment and side effects of the drugs, many patients failed to complete the treatment or stopped the treatment before completion. Also implementation and continuation of this long duration of treatment adds a huge burden to the health system of the country. There were several studies being conducted to shorten the duration of regimen for MDR TB, and in May, 2016, a standardized regimen of 9 to 12-month duration for MDR TB was recommended by WHO.[3] This shorter regimen reported to give relapse free cure in more than 85% of selected MDR TB patients.[4],[5],[6],[7]

The recommended regimen by WHO was used by many countries in several studies and in the STREAM trial.[8] The regimen consists of kanamycin (an injectable agent), moxifloxacin, prothionamide, clofazimine, isoniazid (high dose), pyrazinamide, and ethambutol, given together in an initial phase of 4 months (with the possibility to extend to 6 months if they remain sputum-smear positive at the end of month 4), and followed by 5 months of treatment with four of the medicines (moxifloxacin, clofazimine, pyrazinamide, and ethambutol). Bedaquiline and delamanid are not recommended till date to be included in the shorter regimen of MDR-TB treatment.[3] The dosage schedule for shorter regimen of MDR-TB is summarized in [Figure 1].{Figure 1}

The recommended doses of drugs [Figure 2] in this regimen is based on dosage by weight published by the Global Drug-resistant TB Initiative in 2015 and the STREAM trial.[8],[9] Medicines are taken once per day, all days of the week. In case of prolonged intensive phase, the injectable agent is only given three times a week after the 4th month.{Figure 2}

The shorter MDR-TB regimen may be used in MDR-TB patients who do not have the following conditions[3]:Confirmed resistance, or suspected ineffectiveness, to a medicine in the shorter MDR-TB regimen (excluding resistance to isoniazid)Previous exposure for more than 1 month to a second-line medicine included in the shorter MDR-TB regimenIntolerance to one or more medicines in the shorter MDR-TB regimen or increased risk of toxicity (e.g., drug–drug interactions, cardiotoxicity)PregnancyExtrapulmonary diseaseAt least one medicine in the shorter MDR-TB regimen not available in the program.

Another less common criterion for exclusion from shorter drug regimen is previous exposure to fluoroquinolone or a second-line injectable medicine for more than 1 month, not included in shorter regimen but which may generate cross-resistance, if resistance to both of these two agents has been excluded by a reliable drug susceptibility test (DST), then the shorter MDR-TB regimen can be used. Detection of pyrazinamide resistance at the start of treatment by using a reliable DST may also be considered a criterion for exclusion. There are other circumstances where a clinician can use longer duration of regimen, for example, uncertainty about drug susceptibility; there is no access to second-line LPA; unavailability of one or more medicines; or the patient condition requires immediate start of treatment. The shorter MDR-TB regimen should only be used in whom the diagnosis of RR-/MDR-TB has been reliably confirmed by an approved molecular (e.g., Xpert MTB/RIF) or phenotypic DST method. Children and people with HIV on antiretroviral therapy may receive the shorter MDR-TB regimen.

There are some instances where shorter MDR-TB regimen may be stopped and a longer, individual MDR-TB regimen may be started[3]:DST results taken after start of treatment fail to confirm resistance to rifampicin or even TB (i.e., initial results were not valid);DST results show resistance to medicines in the shorter MDR-TB regimen: this may reflect the actual situation at start of treatment which was unknown at that time, or else the acquisition of additional resistance during treatment;Lack of response to treatment (e.g., no sputum smear conversion by 6 months or deterioration of clinical condition despite treatment);Patient is treated for more than 1 month, interrupts treatment and returns after an interval more than 2 months (i.e., fulfills another exclusion criterion);Emergence of another exclusion criterion (e.g., extrapulmonary disease, pregnancy, intolerance to a medicine in the regimen).

The patients on shorter MTR-TB regimen should be followed up and monitored as same as longer MTR-TB treatment. Response to treatment should be monitored by monthly sputum smear microscopy and mycobacterial culture.

The shorter MDR-TB regimen is a reality, and it should be adapted by the national TB control program in eligible group of MDR-TB patients irrespective of age and HIV status. This regimen can cut the cost burden of treating MDR-TB patients on health system of the country.

References

1World Health Organization. Global tuberculosis report2016 (WHO/HTM/TB/2016.13) [Internet]. Geneva: World Health Organization; 2016. Available from: http://www.who.int/tb/publications/global_report/en/.
2World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis, 2011 update. (WHO/HTM/TB/2011.6) [Internet]. Geneva: World Health Organization; 2011. Available from: http://whqlibdoc.who.int/publications/2011/9789241501583_eng.pdf.
3World Health Organization. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update (WHO/HTM/TB/2016.04) [Internet]. Geneva: World Health Organization; 2016. Available from: http://www.who.int/tb/areas-of-work/drug-resistanttb/treatment/resources/en/.
4Van Deun A, Maug AKJ, Salim MAH, Das PK, Sarker MR, Daru P et al. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am J Respir Crit Care Med 2010;182:684–92.
5Piubello A, Harouna SH, Souleymane MB, Boukary I, Morou S, Daouda M et al. High cure rate with standardized short-course multidrug-resistant tuberculosis treatment in Niger: No relapses. Int J Tuberc Lung Dis 2014; 18:1188–94.
6Aung K, van Deun A, Declercq E, Sarker M, Das P, Hossain M et al. Successful ‘9-month Bangladesh regimen’ for multidrug resistant tuberculosis among over 500 consecutive patients. Int J Tuberc Lung Dis 2014; 18:1180–7.
7Kuaban C, Noeske J, Rieder HL, Aït-Khaled N, Abena Foe JL, Trébucq A. High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon. Int J Tuberc Lung Dis 2015;19:517–24.
8Nunn AJ, Rusen ID, Van Deun A, Torrea G, Phillips PPJ, Chiang C-Y et al. Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): Study protocol for a randomized controlled trial. Trials 2014;15:353.
9Global Drug-resistant TB Initiative (GDI). The evaluation of effectiveness and safety of a shorter standardized treatment regimen for multidrug-resistant tuberculosis [Internet]. Geneva: Stop TB Partnership; 2015. Available from: http://www.stoptb.org/wg/mdrtb/assets/documents/Generic%20protocol%20shorter%20treatment_%202015.pdf.