A 28-year-old woman with newly diagnosed pulmonary tuberculosis is found to be resistant to both isoniazid and rifampicin on drug susceptibility testing. She has no prior TB treatment history. What is the drug of choice for initiating therapy in this case of multidrug-resistant tuberculosis (MDR-TB)?

## Management of Multidrug-Resistant Tuberculosis (MDR-TB) **Key Point:** MDR-TB is defined as resistance to both isoniazid and rifampicin. The backbone of MDR-TB regimens consists of a fluoroquinolone (preferably levofloxacin or moxifloxacin) and bedaquiline, supplemented by other second-line agents. ## MDR-TB Treatment Strategy ### WHO-Recommended Regimen for MDR-TB **High-Yield:** The current WHO-recommended shorter MDR-TB regimen (20 months) includes: - **Bedaquiline** (ATP synthase inhibitor, bactericidal) - **Fluoroquinolone** (levofloxacin or moxifloxacin) — bactericidal - **Linezolid** (protein synthesis inhibitor) — bactericidal - **Pyrazinamide** (if susceptible) - **Ethambutol** (if susceptible) ### Why Fluoroquinolone + Bedaquiline? | Agent | Mechanism | Role in MDR-TB | Advantage | |-------|-----------|----------------|----------| | **Fluoroquinolone** | Inhibits DNA gyrase | Backbone agent | Oral, bactericidal, good lung penetration | | **Bedaquiline** | Inhibits ATP synthase | Backbone agent | Novel mechanism, highly bactericidal, reduces treatment duration | | **Linezolid** | Inhibits protein synthesis | Backbone agent | Excellent intracellular penetration, bactericidal | | **Ethambutol** | Inhibits arabinosyl transferase | Adjunctive | Prevents resistance, bacteriostatic | | **Pyrazinamide** | Inhibits fatty acid synthesis | Adjunctive (if susceptible) | Bactericidal, good penetration | ### Clinical Pearl Bedaquiline is a breakthrough agent for MDR-TB. It is the first new TB drug in 40 years and significantly shortens MDR-TB treatment from 20+ months to 20 months when combined with fluoroquinolones and linezolid. It is now included in all WHO-recommended MDR-TB regimens. **Mnemonic:** **BFL** = **B**edaquiline, **F**luoroquinolone, **L**inezolid — the backbone of modern MDR-TB therapy. ### Treatment Duration - **Intensive phase:** 5–7 months (bedaquiline, fluoroquinolone, linezolid, pyrazinamide, ethambutol) - **Continuation phase:** 13–15 months (fluoroquinolone, bedaquiline, linezolid, ethambutol) **Warning:** Older regimens using thiacetazone, para-aminosalicylic acid (PAS), and streptomycin are no longer recommended due to poor efficacy, toxicity, and the availability of superior agents like bedaquiline and linezolid. [cite:WHO TB Guidelines 2023; NTEP India MDR-TB Guidelines]