Treatment Outcomes in Low-Level Isoniazid Resistant Tuberculosis

Background: Isoniazid (INH) is an important drug in the treatment of Mycobacterium tuberculosis (TB). Resistance to INH is classified as either high-level (MIC > 2 μg/mL) or low-level (MIC 0.2 – 1 μg/mL) resistance. Treatment of high-level resistant TB usually requires discontinuation of INH and, either a more prolonged treatment course, or a greater number of drugs in the continuation phase. Some evidence suggests that including INH in the treatment regimens of low-level resistant strains may be acceptable, as resistance can be overcome when high serum concentrations of INH are achieved. A retrospective study was conducted on all cases of low-level INH resistant TB in Alberta, Canada. The purpose was to determine whether treatment with conventional INH-containing regimens was associated with a higher rate of treatment failure.

Methods: All cases of low-level INH resistant TB in Alberta between 1992 and 2012 were identified using a provincial TB surveillance database. Cases were stratified into two groups based on whether the treatment regimen included INH for the entire duration of therapy or an alternative non-INH containing regimen was used. Data on baseline characteristics of the two groups were obtained, including site of disease, sex, age, country of origin, HIV status and previous TB treatment. The mean duration of therapy in the two groups was determined. Treatment failure was defined as disease relapse at one year through passive surveillance.

Results: 31 cases of low-level INH resistant TB were identified, of which 10 were INH treated and 21 were non-INH treated. There was no difference between the two groups with respect to baseline characteristics. The mean duration of treatment in the INH group was significantly shorter than the non-INH group (8.5 vs. 12.9 months) (p=0.004). One patient was lost to follow up in each group due to relocation from the province. There were no cases of disease relapse identified at one year.

Conclusion: This study supports the use of first line INH-containing regimens in TB cases with low-level INH resistance. Patients who receive INH may receive shorter courses of therapy without an apparent increased risk of early disease relapse. Larger prospective studies are required to further support these findings.