A 45-year-old man on twice-weekly supervised anti-TB therapy repeatedly develops fever with chills, myalgia and headache a few hours after each supervised dose, resolving before the next dose. Blood counts and cultures are unremarkable. The most likely mechanism of this syndrome is:
- A Anti-drug antibody formation triggered by intermittent high-dose rifampicin ✓
- B Direct hepatotoxicity from pyrazinamide accumulation
- C Immune reconstitution inflammatory syndrome
- D Herxheimer reaction from rapid bacillary killing by isoniazid
Correct answer: A. Anti-drug antibody formation triggered by intermittent high-dose rifampicin
Explanation
The influenza-like syndrome with fever, chills and myalgia occurring shortly after a dose is characteristic of intermittent (once or twice weekly) high-dose rifampicin and is immunologically mediated, with anti-rifampicin antibodies; severe cases show haemolysis, shock and acute renal failure. Switching to daily therapy resolves it. Pyrazinamide hepatotoxicity would not recur predictably within hours of each dose.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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