Strains of Mycobacterium tuberculosis resistant to both isoniazid and rifampin are classified as multidrug‑resistant tuberculosis (MDR‑TB). MDR‑TB requires second‑line anti‑tuberculosis drugs, often with longer treatment, greater toxicity, and specialized management including drug susceptibility testing, adherence support, and public‑health measures to prevent spread. Treatment is guided by experts and may include injectables or newer oral agents such as bedaquiline and linezolid.

Mycobacterium tuberculosis is not reliably classified by Gram staining; its lipid‑rich, mycolic acid cell wall resists the Gram stain, so it may appear weakly Gram‑positive or variable. It is classically described as an acid‑fast bacillus—diagnosed by retention of carbol‑fuchsin in Ziehl–Neelsen or fluorescent stains—reflecting its unique, waxy cell envelope.

Rifampin and isoniazid are given together to treat tuberculosis because they attack the bacteria by different mechanisms, producing faster, more complete bacterial killing and reducing the risk that drug‑resistant strains will emerge. Using both drugs improves cure rates, lowers relapse risk, and is a core part of standard combination therapy for active and some latent TB.

Isoniazid is highly selective for Mycobacterium tuberculosis because it’s a prodrug activated by the bacterial catalase–peroxidase enzyme KatG. The activated drug specifically inhibits InhA, an enoyl-ACP reductase required for mycolic acid synthesis in mycobacterial cell walls. Human cells and most other bacteria lack KatG activation and the mycolic acid target, so isoniazid preferentially kills mycobacteria.

The fastest effective cure for pulmonary TB is prompt initiation of standard multi‑drug therapy: a two‑month intensive phase (isoniazid, rifampicin, pyrazinamide, ethambutol) followed by four months of isoniazid and rifampicin. Strict adherence (often under directly observed therapy), regular sputum monitoring, and completing the full course are essential. Drug‑resistant TB needs specialist, longer regimens; good nutrition and avoiding smoking/alcohol aid recovery.

The GenoType MTBDRplus line-probe assay is a molecular test that detects rifampicin and isoniazid resistance in Mycobacterium tuberculosis. It uses PCR with reverse hybridization to identify mutations in the rpoB gene (rifampicin) and katG and inhA regions (isoniazid), providing rapid detection of multidrug-resistant TB from cultured isolates or, in some settings, directly from sputum.