Acquired anti-tuberculosis drug resistance over the course of treatment for multidrug-resistant tuberculosis in Arkhangelsk oblast, Russia Open Access

Smith, Sarah Elizabeth (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/zg64tm83q?locale=en
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Abstract


Introduction: The rise of multidrug-resistant tuberculosis (MDR TB), defined as
Mycobacterium tuberculosis ( M tb) with in vitro resistance to at least rifampin and
isoniazid, poses an enormous threat to global TB control and prevention. The Green
Light Committee (GLC), a subcommittee of the International Working Group on MDR
TB, was created to evaluate, lend guidance and approve MDR TB programs for access to
reduced price, quality-assured second-line drugs, the drugs used to treat MDR TB [1].
Unfortunately, even MDR TB programs that follow GLC guidelines observe
unacceptable percentages of poor treatment outcomes leading one to suspect that M tb
may be acquiring additional drug resistance over the course of treatment [2]. Naturally,
the question arises what is different about patients whose isolates acquire additional drug
resistance over the course of MDR TB treatment? Is the number of effective drugs at the
beginning of treatment for MDR TB associated with less acquired resistance and better
treatment outcomes?
Methods: To address these questions, demographic, clinical and laboratory follow up data
from Arkhangelsk, Russia, a GLC-approved TB program site, were analyzed via multiple
logistic regression modeling techniques to identify risk factors associated with acquired
drug resistance while controlling for potential confounding.
Results: Patients who were treated with at least 4 effective drugs at the beginning of
current MDR TB treatment had a 0.22 risk odds of acquiring drug resistance during
treatment compared to patients who did not receive treatment with at least 4 effective
drugs while controlling for the number positive follow-up cultures and days spent in the
hospital during intensive phase (95% Conf. limit: 0.07, 0.71).
Discussion: Treatment with at least 4 effective drugs from the start of treatment had
protective effects against acquiring drug resistance compared to treatment with fewer
than 4 effective drugs. In other words, patients who were treated with fewer than 4
effective drugs had a significantly increased risk of acquired drug resistance compared to
patients who were treated with at least 4 effective drugs. Future research should
incorporate other aspects of drug effectiveness including dosage and drug quality.

Table of Contents



TABLE OF CONTENTS

Introduction........................................................Page 1
Background.........................................................Page 3
Methods.............................................................Page 15
Results...............................................................Page 23
Discussion...........................................................Page 28
Possible Future Directions......................................Page 33
References..........................................................Page 34
Tables................................................................Page 38
Appendix A: PETTS Patient Data Form......................Page 48
Appendix B: Emory IRB Letter of Exemption................Page 67

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