Effect of Acquired Resistance to Streptomycin or Ethionamide on Treatment Outcomes in Patients with Multidrug-Resistant Tuberculosis Open Access

Panepento, Amanda (Fall 2020)

Permanent URL: https://etd.library.emory.edu/concern/etds/9019s3716?locale=pt-BR%2A
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Abstract

With millions of people contracting it and billions of dollars spent researching and treating it annually, the world-wide burden of tuberculosis (TB) is staggering and thus, many public health organizations are constantly seeking ways to decrease the morbidity, mortality, and the financial burden it places on communities across the globe. What’s especially concerning has been the rising development of bacterial resistance to key antibiotics and the increase in cases of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. This study used data prospectively collected from 1254 subjects in nine countries as part of the Preserving Effective TB Treatment Study (PETTS) to identify whether acquiring resistance to streptomycin or ethionamide is associated with worse outcomes in patients being treated for MDR TB. Consecutive consenting adults ages 18 years and older with pulmonary MDR TB were enrolled. Baseline and monthly sputum samples were collected and sent to the CDC in Atlanta, GA for drug-susceptibility analysis. We developed two multivariable logistic regression models, one for each drug, in order to assess whether developing resistance to either of these drugs during treatment increases the odds of poor treatment outcomes. Among 432 subjects who had M. tuberculosis strains that were susceptible to streptomycin at baseline, 42 (9.7%) of them developed resistance to streptomycin during treatment. Among the 1022 subjects who had strains susceptible to ethionamide at baseline, 176 (17.2%) of them developed resistance to ethionamide. Through our analysis, no significant association between acquired resistance to streptomycin and treatment outcomes was found. In contrast, acquired resistance to ethionamide increased the odds of poor treatment outcomes by 82% (OR = 1.82, 95% CI 1.47 - 2.25, p <0.0001) in patients being treated for MDR TB. Therefore, we concluded that acquired resistance to ethionamide was associated with worse patient outcomes. By increasing our understanding of the impact that acquiring resistance to specific antibiotics has on treatment outcomes, the scientific community can develop better antibiotic therapies to maximize good outcomes for patients with MDR TB.

Table of Contents

Background...........................................................................................................................................1

Methods.................................................................................................................................................3

Results....................................................................................................................................................7

Discussion............................................................................................................................................11

           Strengths & Limitations........................................................................................................12

Conclusion............................................................................................................................................14

References............................................................................................................................................15

Tables....................................................................................................................................................17

Appendices...........................................................................................................................................32

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