**Core Concept**
The development of resistance to Isoniazid (INH) in tuberculosis (TB) patients is often associated with the emergence of resistance to other first-line antitubercular drugs due to the shared mechanism of action and the phenomenon of cross-resistance.

**Why the Correct Answer is Right**
Rifampicin and INH share a common target, the beta-subunit of RNA polymerase, which is essential for bacterial DNA replication and transcription. Mutations in the rpoB gene, which encodes this subunit, can confer resistance to both INH and Rifampicin. This cross-resistance occurs because the same mutations that reduce the efficacy of INH can also decrease the binding affinity of Rifampicin to its target, rendering both drugs less effective against the bacteria.

**Why Each Wrong Option is Incorrect**
**Option A:** Streptomycin is an aminoglycoside antibiotic that targets the bacterial 30S ribosomal subunit. Resistance to Streptomycin is not directly related to INH resistance, as it involves a different target and mechanism of action.
**Option C:** Ethambutol is a bacteriostatic agent that inhibits arabinosyl transferases involved in mycobacterial cell wall synthesis. Resistance to Ethambutol is not directly linked to INH resistance, as it involves a distinct mechanism of action and target.
**Option D:** Pyrazinamide is a prodrug that is activated within acidic environments, such as the phagolysosome of macrophages. Resistance to Pyrazinamide is not directly related to INH resistance, as it involves a different mechanism of action and target.

**Clinical Pearl / High-Yield Fact**
When treating TB patients, it is essential to monitor for cross-resistance between INH and Rifampicin, particularly in regions with high rates of multi-drug resistance. This is because the emergence of resistance to one drug can compromise the efficacy of the entire treatment regimen.

**✓ Correct Answer: B. Rifampicin**