Rifamycins

Mechanism: Rifamycins bind to the beta subunit of bacterial DNA-dependent RNA polymerase, inhibiting RNA synthesis initiation; they are bactericidal against actively dividing Mycobacterium tuberculosis.

Clinical uses: Rifampin is a cornerstone of multidrug TB therapy (RIPE regimen: Rifampin, Isoniazid, Pyrazinamide, Ethambutol) and is used for Mycobacterium leprosy treatment. It is also used for meningococcal and H. influenzae type B prophylaxis in close contacts, and to eliminate nasal carriage of Staphylococcus aureus (often combined with other agents due to rapid resistance development). Rifabutin is preferred over rifampin in HIV patients on protease inhibitors due to less CYP450 induction. Rifapentine has a longer half-life, allowing less frequent dosing in latent TB treatment (e.g., 3HP regimen with isoniazid).

Adverse effects: Hepatotoxicity, orange-red discoloration of body fluids (urine, tears, sweat - can stain contact lenses), flu-like symptoms, thrombocytopenia, and potent induction of cytochrome P450 enzymes leading to numerous drug interactions (reduces efficacy of oral contraceptives, warfarin, protease inhibitors, and other drugs).

Resistance: Rapidly develops with monotherapy due to mutations in rpoB gene encoding RNA polymerase beta subunit; hence always used in combination therapy for active TB.

Mnemonic: 'Rifampin's 4 R's' - RNA polymerase inhibitor, Revs up microsomal (P450) enzymes, Red/orange body fluids, Rapid resistance if used alone.