Directly observed therapy for multidrug-resistant TB decreases mortality

May 21, 2017

ATS 2017, WASHINGTON, DC -- Directly observed therapy (DOT) for multidrug-resistant tuberculosis (MDR TB) was associated with a 77 percent decrease in mortality in the United States, compared to self-administered therapy from 1993 to 2013, according to new research presented at the ATS 2017 International Conference.

DOT is a strategy to ensure that people with TB adhere to a long and challenging drug regimen by having someone observe and record the taking of all medicines. MDR TB is resistant to at least isoniazid and rifampin, two of the main therapeutic agents used to treat TB.

"Directly observed therapy is already recommended to treat all forms of TB, but it's valuable to have this data on the effectiveness among patients with MDR TB," said Jorge Salinas, MD, lead study author and epidemic intelligence service officer in the Centers for Disease Control and Prevention's Division of Tuberculosis Elimination. "We wanted to assess whether the strategy influenced mortality in MDR TB patients."

The researchers analyzed data from 1993-2013 for 3,434 MDR TB patients, 709 of whom died during the follow-up period. The proportion of patients on DOT increased from 74 percent during 1993-2002 to 95 percent during 2002-2013.

Among MDR TB patients in the study:

The study adjusted mortality findings for these and other characteristics and found that across all demographic and clinical groups those who underwent DOT had significantly lower mortality.

"This protective effect may come from DOT alone or from other patient-centered measures, such as transportation assistance or food stamps given along with DOT by TB treatment facilities to improve treatment adherence," Dr. Salinas said. "The findings reinforce that all patients with MDR TB should receive DOT and other patient-centered measures to ensure patients complete their treatment."
Contact for Media: NCHHSTP Media Team,; (404) 639-8895


Dacia Morris
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Session: A26 Diagnosis and Treatment of Tuberculosis
Abstract Presentation Time: Sunday, May 21, 9:15 a.m. ET
Location: Walter E. Washington Convention Center, Room 144A-C (Middle Bldg., Street Level)

Abstract 5304

Factors Associated with Mortality Among Patients with Multidrug-Resistant Tuberculosis--United States, 1993-2013

Authors: J.L. Salinas, L.R. Armstrong, J.P. Cegielski, M.B. Haddad, B.J. Silk; Centers for Disease Control and Prevention - Atlanta, GA/US

Background: Multidrug-resistant tuberculosis (MDR TB) is diagnosed when the patient's Mycobacterium tuberculosis isolate is resistant to at least isoniazid and rifampin. Completing treatment reduces mortality and prevents TB recurrence and transmission to others. Although directly observed therapy (DOT) is standard care for ensuring treatment completion, some patients' therapy is self-administered. In a large cohort of U.S. MDR TB patients, we examined patient and clinical characteristics and treatment administration mode in association with mortality over time.

Methods: We analyzed surveillance data for MDR TB patients treated in the United States during 1993-2013. We used Cox proportional hazards models to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for the association of treatment administration mode (DOT versus self-administered therapy) with all-cause mortality during TB treatment, accounting for age (per 5-year increments), sex, race/ethnicity, HIV infection, previous TB disease, site of disease (i.e., pulmonary versus extrapulmonary), and additional drug resistance (i.e., resistance to at least one fluoroquinolone or a second-line injectable drug). Stratified models were also fit for origin (U.S.-born or foreign-born) and period of treatment (1993-2002 or 2003-2013).

Results: Among 3,434 MDR TB patients, 709 (21%) died during TB treatment. Most patients were foreign-born of Asian (50%) or Hispanic (33%) race/ethnicity. Among those with available data, 710 (34%) had HIV infection reported, 606 (18%) had previous TB disease, and 577 (17%) had additional drug resistance. DOT increased from 74% during 1993-2002 to 95% during 2002-2013; all-cause mortality decreased from 31% to 11% during these periods. Older age (aHR: 1.15; 95% CI: 1.11-1.20) and reported HIV infection (aHR: 7.11; 95% CI: 5.46-9.24) were risk factors for all-cause mortality irrespective of patient's origin or period of treatment. Receiving DOT (aHR: 0.23; 95% CI: 0.19-0.28) was protective in all stratified models.

Conclusions: In the United States, all-cause mortality during treatment has declined among patients with MDR TB. DOT coverage has increased and remained protective over time against all-cause mortality, after adjusting for demographic and clinical characteristics known to be associated with mortality. A continued emphasis on maximizing DOT coverage can help reduce all-cause mortality.

American Thoracic Society

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