**Core Concept**
MDR tuberculosis (TB) is a type of TB infection caused by Mycobacterium tuberculosis that is resistant to at least two of the most powerful first-line anti-TB drugs, isoniazid and rifampicin. This resistance pattern makes MDR TB challenging to treat and increases the risk of transmission to others.

**Why the Correct Answer is Right**
The correct answer is A. Isoniazid + Rifampicin because resistance to these two drugs is the primary definition of MDR TB. Isoniazid is a prodrug that requires activation by the enzyme catalase-peroxidase (KatG) to its active form, isoniazid-NAD+ complex, which inhibits mycolic acid synthesis. Rifampicin, on the other hand, is a potent inhibitor of RNA synthesis by binding to the beta-subunit of RNA polymerase. The combination of resistance to both isoniazid and rifampicin severely limits treatment options and increases the risk of treatment failure.

**Why Each Wrong Option is Incorrect**
**Option B:** Resistance to isoniazid + Pyrazinamide is more commonly associated with XDR TB (Extensively Drug-Resistant TB), not MDR TB.
**Option C:** While resistance to rifampicin + Pyrazinamide is concerning, it is not the primary definition of MDR TB.
**Option D:** Resistance to rifampicin + Ethambutol is also not the primary definition of MDR TB.

**Clinical Pearl / High-Yield Fact**
It's essential to note that MDR TB is often associated with HIV co-infection, which can compromise the host's immune response and increase the risk of TB transmission.

**✓ Correct Answer: A. Isoniazid + Rifampicin**