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6EHR3Z is a combination tuberculosis retreatment regimen consisting of ethambutol, isoniazid, pyrazinamide, and a triple dose of rifampicin (30 mg/kg), administered over a six-month period. Developed by the Institute of Tropical Medicine, Belgium, this regimen is currently being evaluated in Phase 3 clinical trials for the treatment of recurrent pulmonary tuberculosis, particularly in patients with isoniazid-resistant but rifampicin-susceptible strains. The regimen's mechanism of action involves the synergistic effects of its components: rifampicin inhibits DNA-directed RNA polymerase, isoniazid targets enoyl-[acyl-carrier-protein] reductase [NADH] to disrupt cell wall synthesis, ethambutol inhibits arabinosyltransferase to further impair cell wall integrity, and pyrazinamide is thought to target ribosomal protein S1 or disrupt membrane energetics. By employing a high dose of rifampicin, 6EHR3Z aims to provide an effective alternative to fluoroquinolone-containing regimens, thereby helping to prevent the development of further drug resistance.
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