Interventions for Tuberculosis Control and Elimination 2002
Interventions for Tuberculosis Control and Elimination 2002
Interventions for Tuberculosis Control and Elimination 2002
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Differences in bactericidal activity<br />
Isoniazid has the highest early bactericidal activity of all of the anti-tuberculosis<br />
drugs. Thus, isoniazid-resistant mutants may have a selection advantage<br />
over a two-day period. This is not usually relevant, as this advantage<br />
is overcome over the ensuing period. However, should it happen that<br />
treatment is stopped after two days <strong>and</strong> subsequently resumed <strong>for</strong> another<br />
two-day period, the proportion of isoniazid-resistant mutants will have<br />
increased at the end of each cycle (figure 38). 464<br />
Sub-inhibitory concentrations<br />
Whenever sub-inhibitory concentrations of a drug A are being taken, growth<br />
of bacilli susceptible to drug A will be mildly suppressed <strong>and</strong> their natural<br />
re-growth retarded if it is stopped. This does not apply to mutants resistant<br />
to drug A. They will not be affected at all by drug A but only by<br />
other drugs given simultaneously (figure 39). 464 The mutants resistant to<br />
drug A will thus have a selective advantage. This might not be an uncommon<br />
scenario as the number of tablets required to be ingested (including<br />
57<br />
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Figure 37. Special population hypothesis, indicating those bacterial populations<br />
at the start which are killed by the various drugs. Reproduced from456 by the permission<br />
of the publisher Churchill Livingstone.
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