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Antimicrobial Agents

Antimicrobial Agents. Mycobacterium tuberculosis. TB is hard to kill with antibiotics Slow growth Fortified cell wall Intracellular growth Very good at developing resistance to single agents. Treatment of TB – Old School. Surgical collapse of infected lung

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Antimicrobial Agents

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  1. Antimicrobial Agents

  2. Mycobacterium tuberculosis TB is hard to kill with antibiotics Slow growth Fortified cell wall Intracellular growth Very good at developing resistance to single agents

  3. Treatment of TB – Old School Surgical collapse of infected lung Vitamin D & heliotherapy (can you say “melanoma” Bed rest and fresh air

  4. Modern Treatment of TB – A Rigorous Course of Multiple Antibiotics First line drugs Isoniazid Rifampin Ethambutol Streptomycin Pyrazinomide Second line drugs Moxi-or gatifloxacin Ethionamide Aminosalicylic acid Cycloserine Amikacin and kanamycin Capreomycin linezolid 6 months of taking a handful of pills!

  5. Multi-Drug Resistant TB

  6. Isoniazid (INH) Synthetic hydrazide of isonicotinic acid Requires catalase-peroxidase for activation Bacteriocidal for growing cells, static for resting cells Prevents synthesis of mycolic acids

  7. Isoniazid (INH) Oral or parental Water soluble, penetrates into caseous material of granuloma Acetylated and secreted into urine Toxicity Rash and fever Jaundice (rare) Peripheral neuritis (rare)

  8. Rifamycins Natural and semi-derived from filamentous soil bacteria Complex macrocyclic antibiotics Members of the class Rifabutin (for HIV+) Rifapentine Rifampin = rifampicin (for everyone else)

  9. Rifamycins Broad spectrum, bactericidal Inhibit DNA-dependent RNA polymerase Resistance generated by altering target

  10. Rifamycins Administered orally Absorbed in GI tract Asprin will interfere with its absorbance Wide distribution Can discolor body waste, saliva, tears orange-red Acetylated and then excreted into bile and ultimately pooped out

  11. Uses of Select Rifamycins Rifampicin Treatment of TB Prophylaxis against meningocccus Staph infections Rifabutin and rifapentine TB therapy for HIV+ patients MAC infections

  12. Toxicity/Contraindications of Rifamycins Rifampicin Flu-like illness Decreases half life of many drugs by inducing CYPs HIV protease inhibitors and non-nucleoside RT inhibitors Corticosteroids Oral contraceptives Rifambutin Induces CYPs but not to the same degree as rifampicin Polymalgia, pseudojaundice, anterior uveitis

  13. Ethambutol Inhibits arabinosyl transferases involved in cell wall synthesis Given orally and excreted mostly unchanged in the urine Dose dependent diminished visual acuity, red-green color blindness

  14. Pyrazinamide Synthetic pyrazine analog of nicotinamide Bactericidal at weak pH, where TB can be found in MF Inhibits fatty acid synthase I gene

  15. Pyrazinamide Oral administration Excellent penetration Hydrolyzed and hydroxylated before being excreted by kidneys Hepatotoxicity (uncommon) Hyperuricermia – gout (rare)

  16. Mechanisms

  17. The End! Finally…

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