SEARCH-TB of Mtb after HRZE Treatment Interruption in the BALB/c Mouse

Here, we evaluated whether Mycobacterium tuberculosis (Mtb) phenotypes that have a longer duration of drug stress (i.e., longer treatment) have impaired recovery.BALB/c mice were infected with Mtb Erdman via high-dose aerosol then began treatment on infection day 11 with HRZE at standard drug doses 5 of 7 days a week. Treatment was stopped after 2 or 4 weeks and mice sacrificed at intervals during a 28-day treatment interruption period. RNA was immediately preserved and assayed via SEARCH-TB.These results showed that a longer treatment duration impeded Mtb recovery from drug stress to a greater degree than shorter treatment, indicating that chronicity of drug stress may progressively deplete or impair Mtb. This suggests that Mtb may be eliminated via chronic stress and attritional injury. The chronicity of injury and fitness of Mtb to resume growth once treatment is interrupted cannot be measured by enumerating CFU, highlighting the value of SEARCH-TB.