Clinical Pathology: General Principles, Microbiology

• For the agar proportion method, the number of colony-forming units (CFU) growing on drug-containing medium (supplemented 7H10 agar) is compared with the number growing on the drug-free quadrant. If the number of CFU on the drug-containing media is greater than 1% of the CFU on drug-free medium, then the strain is considered resistant.

• There are many mutations in several genes and gene promoter regions that are known to confer isoniazid (INH) resistance in M. tuberculosis. High-level INH resistance is associated with a mutation of the catalase-peroxidase gene (katG) at codon 315. Low-level INH resistance occurs most often as a result of mutation of the promoter of the mabA-inhA gene complex.

• Molecular-based testing for rifampin (RIF) resistance is increasingly used as a surrogate for multi-drug-resistant tuberculosis (MDR-TB), because approximately 95% of RIF-resistant tuberculosis (TB) strains are INH-resistant.

• Select mutations that cause low-level INH resistance also confer ethionamide cross-resistance.

• It has been suggested that patients with low-level INH resistant TB (i.e., INH resistance at 0.2 mg/L [1 μg disk], but susceptibility at 1.0 mg/L [5 μg disk]) may be treated with high-dose INH as part of their regimen. However, the clinical significance and effectiveness of the use of INH in the setting of low-level INH resistance is unclear.