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Prevention of Drug Resistance by Combined Drug Treatment of Tuberculosis

Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 211)

Abstract

Treatment with a combination of anti-tuberculosis drugs is thought to work by the first drug killing mutants resistant to the second drug, while the second drug kills those resistant to the first drug. Combined treatment has been remarkably successful in preventing the emergence of resistance during the treatment of tuberculosis. This success has led to the introduction of multi-drug treatment for leprosy, HIV infections and cancer. Its success in tuberculosis depends on a number of conditions such as the chromosomal nature of drug resistance in Mycobacterium tuberculosis and the absence of plasmids carrying resistance factors as well as the manner in which the bacterial population in tuberculosis does not come into contact with other potentially resistant bacteria. For multi-drug treatment to be effective in preventing resistance, the drugs must be sufficiently active so that each can inhibit all the bacteria in lesions. There must also be effective post-antibiotic lags in growth restarting to prevent growth between doses. Special bacterial populations that are drug tolerant or survive drug action unusually successfully are also a potential source of resistance.

Keywords

Mycobacterium tuberculosis Chromosomal mutation Drug resistance Drug activity Post-antibiotic effect 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Centre for InfectionSt George’s University of LondonLondonUK

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