Write a short note on antitubercular therapy, including multidrug-resistant tuberculosis.

Principles of Antitubercular Chemotherapy

Four principles govern all TB treatment:

1. Multiple drugs in combination — to prevent the emergence of resistance; *M. tuberculosis* populations contain naturally resistant mutants, and monotherapy simply selects them.

2. Adequate duration — because of the slow generation time (12–14 hours) and the existence of dormant, semi-dormant and intracellular bacillary populations requiring sterilising drugs.

3. Regular, uninterrupted intake — supported by directly observed treatment and adherence monitoring.

4. Correct dosage by weight band, with a fixed-dose combination to prevent inadvertent monotherapy.

First-line Drugs

Standard Treatment

Treatment under India's National Tuberculosis Elimination Programme (NTEP) is given free, using daily fixed-dose combinations with weight-band dosing, and supported by adherence monitoring (including digital tools) rather than the older thrice-weekly intermittent regimens.

• Drug-sensitive TB: an intensive phase with four drugs (HRZE) followed by a continuation phase with three drugs (HRE) — conventionally 2 months and 4 months respectively.
• Extended duration for CNS tuberculosis, skeletal and disseminated disease (typically 9–12 months, with steroids in TB meningitis and pericarditis).
• Pyridoxine is given with isoniazid to all patients to prevent neuropathy, and is essential in diabetics, alcohol users, the malnourished, pregnant women and those with HIV or renal failure.
• Nutritional support — India's programme provides direct benefit transfer for nutrition, recognising that malnutrition both predisposes to and worsens TB.

Monitoring: clinical response and weight, follow-up sputum smear or culture at defined intervals, liver function where there is baseline liver disease or symptoms, visual acuity on ethambutol, and active enquiry about adverse effects at every visit.

Managing Adverse Effects

Drug-induced hepatitis is the most important. Suspect it with anorexia, nausea, vomiting, jaundice or abdominal pain.

• Stop all hepatotoxic drugs (H, R, Z) if transaminases exceed five times normal without symptoms, or three times normal with symptoms, or if bilirubin rises.
• Support the patient; use a non-hepatotoxic holding regimen (such as ethambutol with a fluoroquinolone and an aminoglycoside) if treatment cannot be interrupted.
• Reintroduce drugs sequentially once liver function normalises, monitoring closely.

Other management: pyridoxine for neuropathy; stop ethambutol immediately for any visual symptom and refer to ophthalmology; NSAIDs for arthralgia; and counselling about harmless rifampicin discoloration to prevent unnecessary discontinuation.

Drug-resistant Tuberculosis

Causes: inadequate, irregular or incomplete treatment (the dominant cause — "man-made" resistance), monotherapy, poor drug quality, malabsorption, and primary transmission of resistant strains, which now accounts for a substantial proportion of cases in India.

Who to suspect: treatment failure, relapse, treatment after loss to follow-up, contacts of known MDR cases, HIV-positive patients, and those not improving on standard therapy.

Diagnosis — rapid molecular testing is now the standard:

• CBNAAT / Xpert MTB/RIF (and Ultra) — detects *M. tuberculosis* and rifampicin resistance within 2 hours; the recommended initial test for all presumptive TB in India.
• Line probe assay (LPA) — detects resistance to rifampicin, isoniazid and second-line drugs.
• Liquid culture and phenotypic drug susceptibility testing — the reference standard, but slow.
• Universal drug susceptibility testing is now programme policy — every diagnosed patient should have at least rifampicin resistance status determined.

Treatment of MDR-TB: managed under the programme with longer or shorter all-oral regimens built from:

• Group A: bedaquiline, linezolid, levofloxacin or moxifloxacin — the backbone
• Group B: clofazimine, cycloserine
• Group C: ethambutol, delamanid, pyrazinamide, amikacin, ethionamide, para-aminosalicylic acid

Key points: regimens are all-oral wherever possible (injectable agents have largely been abandoned because of ototoxicity), require 6–18 months or longer, and demand close monitoring for QT prolongation (bedaquiline, moxifloxacin, clofazimine), linezolid-induced myelosuppression, peripheral and optic neuropathy, and psychiatric effects of cycloserine. Treatment success is substantially lower than for drug-sensitive disease, and adherence support and counselling are essential because of the duration and toxicity.

Prevention

Early diagnosis and complete treatment of infectious cases (the most effective control measure), contact tracing, TB preventive therapy for household contacts and people living with HIV after excluding active disease, BCG vaccination at birth (which protects against disseminated and meningeal TB in children), airborne infection control in health facilities, addressing malnutrition, diabetes, smoking and indoor air pollution, and active case finding in high-risk groups.