• H = isoniazid
• R = rifampicin
• Z = pyrazinamide
• E = ethambutol

Why all four drugs initially?

1. Rapidly reduces the large bacterial population
   • In the first 2 months, there are many actively multiplying M. tuberculosis bacilli.
   • H and R are strongly bactericidal, so they rapidly reduce bacillary load and infectivity.
2. Prevents emergence of drug resistance
   • A few bacilli may be naturally resistant to one drug.
   • Using several effective drugs together makes it very unlikely that a bacillus resistant to all drugs will survive and multiply.
   • Ethambutol is especially included as a protective drug until susceptibility to H and R is reasonably assured.
3. Pyrazinamide enables short-course treatment
   • Z acts well against intracellular and semi-dormant bacilli in acidic sites, such as within macrophages and caseous lesions.
   • Its use during the initial phase has allowed treatment duration to be reduced from around 18 months to about 6 months.
   • It is most useful early, when this bacillary population is more prominent.
4. FDC improves adherence and avoids inadvertent monotherapy
   • Fewer tablets means better adherence.
   • The patient cannot easily take only one or two drugs and omit the others.
   • This reduces the chance of acquired drug resistance. WHO recommends FDC tablets over separate formulations where feasible for drug-susceptible TB treatment (WHO consolidated TB guidance).

Why not continue HRZE for the whole course?

• Pyrazinamide is stopped because its main benefit is in the early sterilizing phase, while prolonged use adds hepatotoxicity and hyperuricemia risk.
• Ethambutol is usually stopped once H and R susceptibility is established because its main role was resistance protection; prolonged use adds optic neuritis risk.
• Isoniazid + rifampicin are continued because they provide the core sterilizing activity against surviving bacilli.

One-line MBBS answer