Interventions for Tuberculosis Control and Elimination 2002

��� ���
�� �
� ��������� �������
��
�� �
�� �
tuberculosis patients once placed on chemotherapy 29,30,458,459 is largely due
to the use of isoniazid.
Sterilizing activity
�
����
� � � � � �� �� ��
��� �� ���������
Figure 31. Bactericidal activity of isoniazid compared to a four-drug combination
therapy over the first two weeks of treatment. 25
Sterilizing activity is defined as the ability to remove so called “persisters”,
once the large bulk of rapidly growing organisms has been killed. A model
presented by Grosset clarifies these two major components of chemotherapy
(figure 32). 460 Inability to destroy rapidly growing bacilli, located
largely extracellularly, leads to treatment failure, while inability to eradicate
persisters leads to relapse subsequent to treatment completion. Persisters
are bacilli that have a lower metabolic activity and thus replicate much
more slowly than bacilli found in cavity linings. It was postulated that the
efficacy of rifampicin as a sterilizing agent was due to its activity on special
populations. 461 This was tested in an experiment reproducing conditions
appropriate for high and low metabolism of tubercle bacilli, respectively,
using temperature control as the means. 462 At body temperature,
there was only slightly higher activity of rifampicin over isoniazid during
a seven-day period. If pulsed temperature elevation was applied for only
one hour per day to increase metabolism, rifampicin was considerably more
active than isoniazid (figure 33). 462
52