Brief Bactericidal Activity of Anti-Tuberculosis Drugs
Status:
Completed
Trial end date:
2020-09-30
Target enrollment:
Participant gender:
Summary
The investigators will determine the bactericidal activity of high-dose isoniazid against M.
tuberculosis isolates that are (1) susceptible to isoniazid at 2.0 mcg/ml but resistant at
0.1 and 0.4 mcg/ml or (2) susceptible at 0.4 mcg/ml but resistant at 0.1 mcg/ml when tested
in the BD MGIT 960 system. Further, the investigators will investigate the molecular genetic
determinants of these differences in susceptibility.
To achieve these objectives the investigators will carry out an innovative variation on early
bactericidal activity (EBA) study methodology. Patients at risk for drug-resistant TB will be
screened for INH resistance using approved molecular assays. In those with INH-resistant TB,
the investigators will quickly perform phenotypic DSTs using the direct method in the Bactec
Mycobacterium Growth Indicator Tube (MGIT) 960 system, so results will be available within 7
days. If the DST results show the susceptibility patterns noted above, patients will receive
900 mg/d INH (600 mg if <45kg), and assess its effect with serial quantitative sputum
cultures for 6 days. If the concentration of viable bacteria decreases significantly, the
investigators will interpret this to mean the drug is having an effect. If not, the drug is
ineffective. After 6 days, the patients will resume treatment according to national
guidelines.
In case the investigators identify drugs that are effective under these conditions, the
investigators will sequence known and putative genes associated with the action of these
drugs for the mycobacterial isolates from these patients.