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Clin Infect Dis. 2014 Jul 1;59(1):9-15. doi: 10.1093/cid/ciu209. Epub 2014 Apr 11.

Improving outcomes for multidrug-resistant tuberculosis: aggressive regimens prevent treatment failure and death.

Author information

1
Division of Infectious Diseases, Brigham and Women's Hospital.
2
Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
3
Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation.
4
Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
5
Tomsk Penitentiary Services, Ministry of Justice.
6
Tomsk Oblast Tuberculosis Hospital, Russian Federation.
7
Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts.
8
Department of Global Health and Social Medicine, Harvard Medical School Partners In Health, Boston, Massachusetts Partners In Health, Moscow, Russian Federation.

Abstract

BACKGROUND:

Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure.

METHODS:

We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure.

RESULTS:

Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis-MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents-we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29-.94]; P = .030).

CONCLUSIONS:

Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies.

KEYWORDS:

MDR-TB; clinical outcomes; drug resistance; optimized background regimen; treatment

PMID:
24729493
PMCID:
PMC4305127
DOI:
10.1093/cid/ciu209
[Indexed for MEDLINE]
Free PMC Article

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