Extensively drug-resistant tuberculosis and multi-drug resistant TB can be cured if treated with aggressive treatment regimens, according to a study conducted in Lima, Peru, and published Thursday in the New England Journal of Medicine, the Wall Street Journal reports. XDR-TB is resistant to the two most potent first-line treatments and at least two of the classes of second-line drugs.

According to the Journal, some forms of drug-resistant TB have "caused alarm" among public health workers worldwide by "raising the prospect" that it cannot be treated effectively with available drugs. A 2006 study conducted in South Africa found that 52 of 53 XDR-TB patients died within a relatively short time of diagnosis (Winstein, Wall Street Journal, 8/7). All of the people with XDR-TB in the South African study were HIV-positive (GlobalHealthReporting.org, 9/5/06). None of the XDR-TB patients in the Peruvian study were HIV-positive, according to the Journal (Wall Street Journal, 8/7).

For the study, which was funded by the Bill and Melinda Gates Foundation, Carole Mitnick of the Department of Social Medicine at Harvard Medical School and colleagues studied 650 patients with drug-resistant TB in Lima between 1999 and 2002. Among the patients, 48 had XDR-TB (CBC News, 8/6).

The researchers conducted drug susceptibility tests in a laboratory to determine which antibiotics might be effective and then aggressively treated patients despite severe side effects (Wall Street Journal, 8/7). The drug susceptibility testing allowed scientists to develop and adjust treatment regimens "containing at least five drugs that were likely to be effective" in an effort to "maximize the chemotherapeutic benefit," according to the study.

The participants were then offered no-cost individualized treatment, surgery to remove infected tissue, and nutritional and psychological support. The treatment was "protracted" and lasted "more than two years in most patients," according to the study (Emery, Reuters, 8/6). In addition, health care workers had frequent contact with the XDR-TB patients to ensure treatment adherence and to monitor for potential side effects (CBC News, 8/6).

Following treatment, 29, or 60%, of the 48 XDR-TB patients were considered cured when TB bacteria did not appear in repeated lab tests. As of 2007, 11 of the XDR-TB patients, or 23%, had died of the disease (Wall Street Journal, 8/7). Among the 603 patients with MDR-TB, 66% were cured of the disease following treatment (Reuters, 8/6).

According to Mitnick, the findings show that aggressive treatment for drug-resistant TB should be expanded (Wall Street Journal, 8/7). "It's essential that the world know that XDR-TB is not a death sentence," Mitnick said in a statement, adding that the study demonstrates that "effective treatment does not require hospitalization or indefinite confinement of patients."

Related Study
A related study, also published Tuesday in NEJM, found that patients with XDR-TB treated at National Jewish Health in Denver were nearly eight times more likely to die than patients with MDR-TB. For the study, Michael Iseman of NJH studied 174 patients with drug-resistant TB, 10 of whom had XDR-TB and 164 of whom had MDR-TB. Half of the 10 XDR-TB patients and 14 of the MDR-TB patients died following treatment. Iseman said that physicians "have become quite proficient at treating" MDR-TB "with initial treatment success rates greater than 90% in recent years." However, Iseman added that XDR-TB cases "are much more difficult to treat" and that doctors "still lose more of these patients than [they] save."

Related Commentary
The findings of the Peruvian study are "encouraging" and "constitut[e] a true change in the current perception of [XDR-TB] as a virtual death sentence," Mario Raviglione, director of the World Health Organization's Stop TB Department, writes in an accompanying NEJM commentary, adding that the "challenge is to make this approach a sustainable reality worldwide." Raviglione noted that the study did not report on the frequency or seriousness of the side effects. In addition, the study raised the question of why similar TB treatment programs in the U.S. and Europe have not achieved comparable success, Raviglione says. According to Raviglione, it is possible the XDR-TB strains in Peru were less drug-resistant than the strains found in the U.S. or Europe (Reuters, 8/6).

NPR's "All Things Considered" on Wednesday reported on the study. The segment includes comments from Mitnick; Raviglione; and Jennifer Furin, Partners in Health country director in Lesotho (Knox, "All Things Considered," NPR, 8/6). Audio of the segment is available online.


The Peruvian study is available online.

The Denver study also is available online.