Introduction Drugs rifamycins isoniazid pyrazinamide ethambutol dapsone clofazimine streptomycin Clinical use Classic Treatment Paradigm for Mycobacteria Organism Prophylaxis Treatment Mycobacterium tuberculosis Isoniazid Active infection: RIPE therapy Rifampin Isoniazid Pyrazinamide Ethambutol Latent infection: isoniazid x 9 months Mycobacterium avium-intracellulare Azithromycin Rifabutin Azithromycin + ethambutol Can also add rifabutin or ciprofloxacin Mycobacterium leprae - Tuberculoid: dapsone + rifampin Lepromatous: dapsone + rifampin + clofazimine Anti-Mycobacterial Medications Drug Mechanism of Action Adverse Effects Notes Rifamycins (rifampin and rifabutin) Inhibits DNA-dependent RNA polymerase Hepatotoxicity Red or orange body fluids CYP450 inducer Cutaneous flushing Rifabutin has less CYP450 effect, thus favored for HIV patients Mutations occur due to decreased binding to RNA polymerase Resistance occurs rapidly if used as monotherapy Isoniazid Inhibits synthesis of mycolic acids Hepatotoxicity Inhibits CYP450 Drug-induced systemic lupus erythematosus Vitamin B6 deficiency peripheral neuropathy sideroblastic anemia co-administer with pyridoxine (B6) to reduce side effects May be used as monotherapy for prophylaxis and latent TB Mutations occur due to underexpression of enzyme required to convert drug into active metabolite Pyrazinamide Unknown but may work through host phagolysosomes Hepatotoxicity Hyperuricemia Arthralgias - Ethambutol Inhibits arabinosyltransferase and disrupts cell wall carbohydrate polymerization Optic neuropathy red-green color blindness Drug resistance due to increased production of arabinosyltransferase Dapsone Inhibits dihydropteroate synthesis (anti-folate) Methemoglobinemia Hemolysis (G6PD deficiency patients) - Clofazimine Disrupts DNA Gastrointestinal upset Dry skin Pink/brown skin and body fluid dyspigmentation - Streptomycin Interacts with 30S ribosomal subunit Tinnitus Vertigo Ataxia Renal toxicity Second-line treatment for M. tuberculosis