Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

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Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

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Title: Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality
Author: Mitnick, Carole Diane; Franke, Molly Forrest; Rich, Michael Leonard; Alcantara Viru, Felix A.; Appleton, Sasha C.; Atwood, Sidney S.; Bayona, Jaime N.; Bonilla, Cesar A.; Chalco, Katiuska; Fraser, Hamish S. F.; Furin, Jennifer J.; Guerra, Dalia; Hurtado, Rocio M.; Joseph, Keith; Llaro, Karim; Mestanza, Lorena; Mukherjee, Joia S.; Muñoz, Maribel; Palacios, Eda; Sanchez, Epifanio; Seung, Kwonjune J.; Shin, Sonya S.; Sloutsky, Alexander; Tolman, Arielle W.; Becerra, Mercedes C.

Note: Order does not necessarily reflect citation order of authors.

Citation: Mitnick, Carole D., Molly F. Franke, Michael L. Rich, Felix A. Alcantara Viru, Sasha C. Appleton, Sidney S. Atwood, Jaime N. Bayona, et al. 2013. Aggressive regimens for multidrug-resistant tuberculosis decrease all-cause mortality. PLoS ONE 8(3): e58664.
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Abstract: Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.
Published Version: doi:10.1371/journal.pone.0058664
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