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Chapter 89

Chapter 89. Antimycobacterial Agents: Drugs for Tuberculosis, Leprosy, and Mycobacterium avium Complex Infection. Tuberculosis, Leprosy, and Mycobacterium avium Complex Infection. Caused by these three species of mycobacteria Mycobacterium tuberculosis Mycobacterium leprae

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Chapter 89

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  1. Chapter 89 Antimycobacterial Agents: Drugs for Tuberculosis, Leprosy, and Mycobacterium avium Complex Infection

  2. Tuberculosis, Leprosy, and Mycobacterium avium Complex Infection • Caused by these three species of mycobacteria • Mycobacterium tuberculosis • Mycobacterium leprae • Mycobacterium avium

  3. Treatment for Mycobacterial Infections • Slow-growing microbes • Requires prolonged treatment • Drug toxicity and poor patient adherence • Promotes drug-resistant mycobacteria emergence

  4. Tuberculosis • Global epidemic • Approximately 2 billion infected worldwide • Kills approximately 2 million/year • New cases in U.S. are declining • Cases increasing outside U.S. • 95% occur in developing countries • Increase due to AIDS and emerging multidrug-resistant mycobacteria

  5. Tuberculosis • Pathogenesis • Mycobacterium tuberculosis • May be limited to lungs or may disseminate • Bacteria quiescent • No obvious symptoms • U.S. – approximately 10 million people harbor tubercle bacilli but show no symptoms

  6. Tuberculosis • Primary infection • Transmitted from person to person • Inhalation of infected, aerosolized sputum • Coughing, sneezing • Initial infection in lung • Immunity usually develops within a few weeks • 90% with normal immune systems never develop clinical or radiologic evidence of TB

  7. Tuberculosis • Immune system failure to control primary infection – TB develops • Necrosis and cavitation of lung tissue • Severe destruction without treatment • Reactivation • Renewal of dormant tubercle bacilli • 60% of new infections may be caused by reactivation

  8. Tuberculosis • Treatment overview • More effective drugs make hospitalization generally unnecessary. • Always treat with two or more drugs. • Direct observation of drug administration is considered standard care. • Treatment is considered effective when no mycobacteria are observed in sputum and no colonies are present in culture.

  9. Tuberculosis • Diagnosis • Indications for testing • Definitive diagnosis • Chest x-ray • Sputum culture • Evaluation of drug susceptibility

  10. Causes of Drug Resistance • Some infecting bacilli inherently resistant • Some develop resistance over course of treatment • Resistance to one drug versus many drugs • Infection with resistant TB acquired through: • Contact with someone who harbors resistant bacteria • Repeated ineffectual courses of therapy

  11. Multi-Drug Resistance With Tuberculosis • Multidrug-resistant TB (MDR TB) • Resistant to both isoniazid and rifampin • Extensively drug-resistant TB (XDR TB) • Resistant to: • Isoniazid (INH) and rifampin • All fluoroquinolones • At least one of the injectable second-line drugs

  12. Treatment Regimens for Tuberculosis • The prime directive of treatment: ALWAYS treat tuberculosis with two or more drugs!

  13. Treatment Regimens for Tuberculosis • Determine drug sensitivity • Treatment regimens – two phases • Induction phase • Eliminate actively dividing tubercle bacilli • Continuation phase • Eliminate intracellular “persisters”

  14. Treatment Regimens for Tuberculosis • Drug-sensitive tuberculosis • Isoniazid or rifampin-resistant tuberculosis • MDR TB and XDR TB • Patients with TB and HIV infection • Duration of treatment • Minimum 6 months for drug-sensitive TB • Up to 24 months for MDR or HIV/AIDS

  15. Promoting Treatment Adherence • Direct observation therapy (DOT) • Patient nonadherence • Allows for ongoing assessment of clinical signs • Intermittent dosing • 2-3 times a week

  16. Evaluation of Treatment • Three modes to evaluate therapy • Bacteriologic evaluation of sputum • Clinical evaluation • Chest radiographs

  17. Diagnosis and Treatment of Latent Tuberculosis • 9-14 million people in U.S. have LTB • 5%-10% will develop active TB without treatment • Targeted TB testing • Who should be tested? • Testing for latent TB • TB skin test (TST) • QuantiFERON-TB Gold (QFT-G) blood test

  18. Diagnosis and Treatment of Latent Tuberculosis • INH • Treatment of choice • Drawbacks of INH • Short-course therapy: rifampin alone • Short-course therapy: rifampin plus pyrazinamide • Vaccination against tuberculosis

  19. Antituberculosis Drugs • First-line drugs • Isoniazid, rifampin • Rifapentine, rifabutin, pyrazinamide, and ethambutol • Second-line drugs • Levofloxacin, moxifloxacin, kanamycin, amikacin, capreomycin, para-aminosalicylic acid, ethionamide, and cycloserine

  20. Isoniazid • Primary agent • Bactericidal • Adverse effects • Peripheral neuropathy (pyridoxine, vitamin B6) • Hepatotoxicity • Optic neuritis • Anemia

  21. Rifampin (Rifadin) • Broad-spectrum antibiotic • Uses • Tuberculosis • Leprosy • Haemophilus influenzae • Legionella

  22. Rifampin (Rifadin) • Adverse effects • Hepatotoxic/hepatitis • Discoloration of body fluids • GI disturbances • Drug interactions • Induces P450 – can hasten drug metabolism • Oral contraceptives • Warfarin • Drugs for HIV infection

  23. Pyrazinamide • Bactericidal to M. tuberculosis • Use • Tuberculosis • Adverse effects • Hepatotoxicity • Hyperuricemia • GI disturbances

  24. Ethambutol (Myambutol) • Bacteriostatic • Use • Tuberculosis • Adverse effects • Optic neuritis • Allergy • Hyperuricemia

  25. Second-Line Anti-TB Drugs • Fluoroquinolones • Injectable drugs • Capreomycin • Kanamycin and amikacin • Other second-line drugs • Para-aminosalicylic acid • Ethionamide • Cycloserine • R207910

  26. Leprosy (Hansen’s Disease) • Chronic infection • Caused by M. leprae • Causes gross disfiguration if untreated • Most can be cured with drug treatment • Affects skin, peripheral nerves, and mucous membranes of upper respiratory tract

  27. Leprosy (Hansen’s Disease) • Overview of treatment • Multidrug therapy • Monotherapy will cause resistance • World Health Organization (WHO) recommends 12 months treatment with three drugs: • Rifampin, dapsone, clofazimine • The ROM regimen

  28. Mycobacterium avium Complex Infection • Mycobacterium avium complex • M. avium • M. intracellulare • Colonization begins in the lungs or GI tract • May spread to the blood, bone marrow, liver, spleen, lymph nodes, brain, kidney, and skin

  29. Mycobacterium avium Complex Infection • Prophylaxis • Azithromycin • Clarithromycin • Acute infection • Same as prophylaxis • Plus ethambutol • Plus rifampin or rifabutin • Additional drugs may also be added

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