Snapshot A 43-year-old woman presents to the emergency room for fevers and a chronic cough. She has a history of HIV infection and has been using antiretrovirals intermittently. She recently lost her job and has been spacing out her medications in hopes of making it last. She is also currently homeless and relies on homeless shelters around the city. She reports that she has been having low-grade fevers, night sweats, and cough. A chest radiograph shows a cavity in the apex of the right upper lobe and hilar adenopathy. She is started on multi-drug anti-tuberculosis therapy, including rifabutin. (Tuberculosis) Introduction Drugs rifampin 4 Rs RNA polymerase (DNA-dependent) inhibitor Ramps up cytochrome P-450 (CYP450) system Results in Red body fluids Resistance if used alone rifabutin less CYP450 stimulation Mechanism of action inhibits DNA-dependent RNA polymerase penetrates tissue to reach granulomas Mechanism of resistance mutations in RNA polymerase to prevent drug from binding Clinical use rifampin Mycoplasma tuberculosis (TB) always used with other anti-TB drugs (RIPE therapy – Rifampin, Isoniazid, Pyrazinamide, and Ethambutol) Mycoplasma leprae long-term treatment with dapsone for tuberculoid form Neisseria meningitidis prophylaxis for the exposed Haemophilus influenzae type b prophylaxis for the exposed rifabutin Mycoplasma avium-intracellulare adjuvant treatment with azithromycin and ethambutol HIV infection rifampin reduces protease inhibitor concentrations through CYP450, so rifabutin is used in HIV patients who require a rifamycin drug Adverse effects hepatotoxicity (hepatitis) ↑ CYP-450 red/orange body fluids (benign) acute interstitial nephritis