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 MedicationsDrugMechanism of ActionAdverse EffectsNotes<p>Rifamycins (rifampin and rifabutin)</p><ul><li>Inhibits DNA-dependent RNA polymerase</li></ul><ul><li>Hepatotoxicity</li><li>Red or orange body fluids<a title="question" href="#217144" link-extracted="true"><img src="/images/question.png" alt=""></a></li><li>CYP450 inducer</li></ul><ul><li>Rifabutin has less CYP450 effect, thus favored for HIV patients</li><li>Mutations occur due to decreased binding to RNA polymerase</li><li>Resistance occurs rapidly if used as monotherapy</li></ul>Isoniazid<ul><li>Inhibits synthesis of mycolic acids</li></ul><ul><li>Hepatotoxicity</li><li>Inhibits CYP450</li><li>Drug-induced systemic lupus erythematosus</li><li>Vitamin B6 deficiency<ul><li>peripheral neuropathy</li><li>sideroblastic anemia</li></ul><ul><li>co-administer with pyridoxine (B6) to reduce side effects<a title="question" href="#217124" link-extracted="true"><img src="/images/question.png" alt=""></a></li></ul></li></ul><ul><li>May be used as monotherapy for prophylaxis and latent TB</li><li> Mutations occur due to underexpression of enzyme required to convert drug into active metabolite</li></ul>Pyrazinamide<ul><li>Unknown but may work through host phagolysosomes</li></ul><ul><li>Hepatotoxicity</li><li>Hyperuricemia</li></ul> -Ethambutol<ul><li>Inhibits arabinosyltransferase and disrupts cell wall</li></ul><ul><li>Optic neuropathy<ul><li>red-green color blindness</li></ul></li></ul>-Dapsone<ul><li>Inhibits dihydropteroate synthesis (anti-folate)</li></ul><ul><li>Methemoglobinemia</li><li>Hemolysis (G6PD deficiency patients)</li></ul>-Clofazimine<ul><li>Disrupts DNA</li></ul><ul><li>Gastrointestinal upset</li><li>Dry skin</li><li>Pink/brown skin and body fluid dyspigmentation</li></ul>-Streptomycin<ul><li>Interacts with 30S ribosomal subunit</li></ul><ul><li>Tinnitus</li><li>Vertigo</li><li>Ataxia</li><li>Renal toxicity</li></ul><ul><li>Second-line treatment forM. tuberculosis</li></ul> Anti-Mycobacterial Medications Drug Mechanism of Action Adverse Effects Notes