Question
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- (a) Drug treatment of pulmonary Tuberculosis. ( 6 mark(s)
- (b) Add a note on Extremely drug resistant TB. 2 mark(s)
Answer
a) Drug treatment of pulmonary tuberculosis Standard therapy uses a two-phase regimen:
- Intensive phase (2 months): four drugs — Isoniazid, Rifampicin, Pyrazinamide, Ethambutol — targeting the large, actively multiplying bacterial population, achieving rapid load reduction and rendering the patient non-infectious relatively quickly.
- Continuation phase (4 months): typically Isoniazid and Rifampicin alone — by this stage the actively-dividing population is substantially reduced, and the goal shifts to sterilizing slower-growing/persister organisms and preventing relapse.
Multiple drugs are used together throughout, since the statistical probability of a bacterium being spontaneously resistant to two or more unrelated drugs simultaneously is vanishingly small — the core rationale for combination therapy in TB, preventing selection of resistant mutants that monotherapy would allow to emerge.
Brief mechanisms: Isoniazid — inhibits mycolic acid synthesis (InhA), bactericidal against actively dividing organisms. Rifampicin — inhibits bacterial RNA polymerase, active against both dividing and semi-dormant organisms. Pyrazinamide — active specifically in the acidic intracellular/caseous environment. Ethambutol — inhibits arabinosyl transferase (cell wall arabinogalactan synthesis), primarily bacteriostatic, included to prevent resistance emergence to the other agents.
b) Extensively drug-resistant TB (XDR-TB) MDR-TB (resistant to at least isoniazid and rifampicin, the two most potent first-line agents) plus additional resistance to a fluoroquinolone and at least one second-line injectable agent — a progressively narrower, more dangerous resistance pattern with substantially poorer treatment outcomes, requiring longer, more toxic regimens with newer agents (bedaquiline, linezolid). It underscores why the multi-drug, full-course, directly-observed-therapy approach to standard TB treatment exists specifically to prevent this escalation from occurring in the first place.