Extensively Drug-Resistant TB Curable With Aggressive Outpatient Treatment

Aggressive treatment of extensively drug-resistant TB (XDR-TB) in HIV-negative patients can achieve high cure rates even in developing countries, a new study finds.

Defined as "Mycobacterium tuberculosis strains with resistance to at least isoniazid, rifampin, and members of three of six classes of second-line drugs," XDR-TB was first identified in 2006; it now been found in 49 countries.

Dr. Carole D. Mitnick of Harvard Medical School and colleagues studied a cohort of patients in Lima, Peru, referred for free individualized therapy from February 1999 to July 2002, following failure of first-line TB treatment. Of the 651 patients, 603 had multidrug-resistant TB (MDR-TB) and 48 had XDR-TB.

Drug regimens to which the XDR-TB isolates were not resistant were developed. These consisted of at least five agents -- including fluoroquinolone, cycloserine, and an injectable agent (streptomycin, amikacin, capreomycin or kanamycin) -- at the highest tolerated doses.

The researchers' approach included daily supervised treatment, drug adjustment when indicated by monthly bacteriologic assessment and repeated drug-susceptibility testing, adverse-event management, and nutritional and psychosocial support. Median treatment duration was 24.9 months.

Of the XDR-TB patients, 29 (60 percent) completed treatment or were cured. Compared with MDR-TB cases, those with XDR-TB had undergone more treatment regimens (mean 4.2 vs. 3.2), had isolates resistant to more drugs (mean 8.4 vs. 5.3), and had longer time to conversion to a negative culture (median 90 days vs. 61 days). However, there was no difference in frequency of cure or relapse or risk of death between the groups.

Mitnick's team noted that "the outcomes in our study were better than most outcomes reported from hospitals in Europe, the United States, and Korea," where cure rates among XDR-TB patients were less than 50 percent. "Our study shows that effective treatment does not require hospitalization or indefinite confinement of patients."

In a related editorial, Dr. Mario C. Raviglione of the World Health Organization said that in order to make the study approach a "sustainable reality worldwide," action "borne out of clear planning, financial commitment and adequate resources, technical capacity and partnership" is needed.

The study, "Comprehensive Treatment of Extensively Drug-Resistant Tuberculosis," and the editorial, "Facing Extensively Drug-Resistant Tuberculosis - A Hope and a Challenge," were published in the New England Journal of Medicine (2008;359(6):563-574 and 636-638, respectively).

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