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

Abstract

RationaleA 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.ObjectivesThis 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.MethodsThis 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 ResultsIn 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).ConclusionsThe 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.

Treatment Outcomes for Patients with Multidrug-Resistant Tuberculosis in Post-Earthquake Port-au-Prince, Haiti

“…Some of these patients posed major challenges for medical management in the setting of a field hospital under tents: 18% of patients had hemoptysis, and 20% of patients required supplemental oxygen. Factors that contributed to the success of treatment in our cohort included the low mean resistance to first-line drugs (19% of the patients had isolates resistant to isoniazid and rifampin only), the aggressive empiric drug regimens used, 14,15 and the dedication of the staff.…”

Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis

“…Fluoroquinolones are among the most effective drugs available for the treatment of MDR TB (1,2). The importance of the fluoroquinolone drug class is implied in how extensively drugresistant (XDR) TB is defined, i.e., as MDR TB with additional in vitro resistance to second-line injectables and any member of the fluoroquinolone drug class.…”

Novel laboratory diagnostic tests for tuberculosis and their potential role in an integrated and tiered laboratory network

“…In addition, quantitative drug susceptibility testing may be indispensable to select drugs to develop so-called aggressive (min. 5 drug) regimens and maintain such therapies in case of toxicity or development of additional drug resistance during therapy [15,16]. Broader access to whole genome sequencing offers the potential to identify more accurate or novel molecular markers that can be correlated to different levels of conventional DST results with the hope that in the near future one may rely more on the result of molecular testing to timely determine individualized treatment regimens for drug resistant patients [17].…”