Acquired anti-tuberculosis drug resistance over the course of treatment for multidrug-resistant tuberculosis in Arkhangelsk oblast, Russia Open Access
Smith, Sarah Elizabeth (2012)
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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