High-dose isoniazid for TB with low-to-moderate isoniazid resistance after 1 week of treatment.

OBJECTIVES

To evaluate the effect of high-dose isoniazid in patients with isoniazid-resistant TB by its bactericidal activity after 1 or more weeks of treatment.

SUBJECTS AND METHODS

Using the rapid direct method of phenotypic drug susceptibility testing, we screened persons with positive sputum microscopy results and genotypic drug resistance for isoniazid resistance. Those with no growth at a critical concentration of 2.0 mg/L were invited to participate in a trial of high-dose isoniazid monotherapy lasting 6 days. After 3 days of no treatment, patients received isoniazid 15 mg/kg and were followed with serial quantitative sputum cultures from Days 0 to 6.

RESULTS

We enrolled 15 patients after a median of 2 weeks standard first-line treatment. Their median bacillary count on Day 0 was 4.9 log cfu/mL on solid agar, and the time to detection (TTD) was 200 h in liquid medium. Neither metric showed meaningful change in bacillary burden over 6 days, declining by a non-significant 0.08 log cfu/mL/d on solid media and slowing TTD by 23 h. These effects did not differ by degree of isoniazid resistance or specific ( gene mutations.

CONCLUSIONS

The utility of high-dose isoniazid against low-level isoniazid resistance beyond the first 2 weeks of chemotherapy should be reconsidered.