The WHO shorter MDR-TB regimen: who will benefit with it?

Abstract

Current treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging since it requires the use of more expensive and toxic drugs that must be administered for a much longer time to achieve relapse free-cure and with much less satisfactory outcomes.

Early results from observational studies in Bangladesh, Cameroon and Niger using regimens lasting 12 months or less have shown a much higher likelihood of treatment success compared with longer conventional regimens.Given the published data and potential impact of shorter regimens on treatment cost and affordability,the World Health Organization (WHO) is now recommending in its 2016 MDR-TB guideline a new short-course regimen that consists of a 4-6 month intensive phase including kanamycin, moxifloxacin, ethionamide, clofazimine, pyrazinamide, high-dose isoniazid and ethambutol and a 5-month continuation phase that includes moxifloxacin, clofazimine, pyrazinamide, and ethambutol.There are very clear criteria regarding what MDR-TB patients would benefit from this regimen.WHO recommends that patients are tested for susceptibility or resistance to fluoroquinolones and to the second-line injectable agent used in the regimen beforebeing started on a shorter MDR-TB regimen. However, in the absence of such testing, patients who are highly unlikely to be infected with resistant strains based on history of exposure, use of second-line medicines at country level or recent representative surveillance data may also be eligible for the shorter MDR-TB regimen.

Recently published data on patients with MDR-TB from Europe suggest that actually, less than eight percent of patients with MDR-TB in the region would be eligible for the short-course treatment regimen proposed by WHO due to the presence of resistance to other drugs in the regimen besides rifampin and isoniazid.

The empirical implementation of this short-course regimen in patients with undiagnosed greater resistance than that for isoniazid-rifampin will surely lead to an extension of resistance to other drugs in the regimen, and to high rates of treatment failure. Comprehensive drug susceptibility testing for first and second-line drugs should be carried out in every MDR-TB patient that will be treated with a short-course regimen.