Micro2- Macrolides

  1. Macrolides are NOT useful against... (3)
    • Enterobacteriacea (acquired)
    • Pseudomonas (intrinsic)
    • Enterococcus (acquired)
  2. What drugs are in the macrolide class? (7)
    • Erythromycin
    • Tylosin
    • Spiramycin
    • Tilmicosin
    • Tulathromycin
    • Clarithromycin
    • Azithromycin
  3. What drug is the class representative of macrolides?
  4. Describe the pharmcokinetic properties of erythromycin. (5)
    • orall bioavailable if enterically coated
    • high Vd- does cross BBB
    • gets intracellular
    • good for respiratory
    • almost exclusive biliary excretion
  5. Erythromycin is not a good ________ drug because...
    UTI; it is not renally excreted
  6. What are some side effects of erythromycin? (2)
    • Promotility- (sometimes desirable, used as pro-motility drug) motilin receptor agonist, stimulates MMCs--> diarrhea and disrupts flora
    • Irritation- injection site redness
  7. What are macrolide drug interactions?
    • inhibits cytochrome P450, may need to decrease dose of other drugs
    • (Azithro is only one that does not do this)
  8. What are the new generation macrolides and what are advantages?
    • Azithromycin, Clarithromycin
    • fewer GI side effects
    • higher gram - activity
    • excellent intracellular and respiratory concs (others have this too)
  9. What is the general spectrum of macrolides?
    • Best for aerobic/ fac Gram +
    • good Gram + coverage- aerobes and anaerobes
    • some Gram - coverage for aerobes and anaerobes
    • [varies by drug]
  10. What are clinical applications of Clarithromycin? (3)
    • Rhodococcus equi with Rifampin
    • Canine Nocardia and rapidly growing Mycobacteria
  11. What are clinical applications of Azithromycin? (2)
    • Dogs- Bartonella (questionable)
    • Cats- URI
  12. What are resistance mechanisms to macrolides? (3)
    • Acquired via plasmids and transposons (G+, G-)
    • Target site modification (G+)- methylation of RNA, encoded by erm genes
    • Efflux pump (G+) encoded by mef gene
  13. What is the MOA of macrolides?
    inhibits protein synthesis by binding the 50S ribosome and preventing tRNA translocation
  14. What are pharmacodynamic properties of macrolides?
    • bacteriostatic
    • Time>MIC
  15. What is the MOA of lincosamides?
    inhibits protein synthesis by binding the 50S ribosome and preventing tRNA translocation
  16. What are pharmoacodynamic properties of lincosamides?
    • Bacteriostatic
    • Time>MIC
  17. What are pharmacokinetic properties of lincosamides? (3)
    • high Vd- crosses BBB, bone, rep penetration
    • good oral absorption (better on empty stomach)
    • eliminated in bile and urine (still not a good UTI drug tho)
  18. What is the spectrum of lincosamides?
    • Gram + aerobes and anaerobes
    • Gram - anaerobes
  19. What drugs are members of the lincosamide class? (2)
    • Clindamycin
    • Lincomycin
  20. What microbes have intrinsic resistance to lincosamides?
    • Enterococcus
    • Enterobacter
    • Pseudomonas
  21. What organisms other than bacteria are lincosamides useful for?
    anti-protozoal at higher doses
  22. What are drug interactions with lincosamides? (3)
    • synergistic with metronidazole when treating B. fragilis
    • antagonizes macrolides and chloramphenical (50S binding site is very close)
  23. What are toxicities of lincosamides? (2 species)
    • Horses- fatal C. diff diarrhea and pseudomembranous colitis
    • Dogs- mild hepatotoxicity, hypersensitivity, diarrhea
  24. What are clinical applications of Clindamycin in dogs and cats? (4)
    • Staph (maybe MR organisms)
    • Strep
    • Anaerobic infections (mouth, peritonitis, severe pneumonia)
    • high dose for toxoplasmosis
  25. What are resistance mechanisms to lincosamides? (1)
    • encoded by erm genes- methylation of adenine in 50S rRNA
    • consistutive and inducible expression of resistance genes (exposure to a macrolide activates gene expression)
  26. How do you test for lincosamide resistance?
    • D-test tests for inducible clinda resistance
    • don't trust a lab report (S) if it doesn't include the D-test
  27. What is the spectrum of Rifampin?
    • primarily Gram + aerobes/ facs
    • SOME gram + anaerobes
    • some Mycobacteria
  28. What microbes have intrinsic resistance to Rifampin? (2)
    • Enterobactericiaea
    • Pseudomonas
  29. What are pharmacodynamic properties of Rifampin?
    • Bacteriostatic (or cidal?)
    • AUC:MIC
  30. What are pharmacokinetic properties of Rifampin? (4)
    • orally bioavailable
    • high Vd- crosses BBB, gets into milk, bone, abscesses
    • hepatic metabolism- deacetylation and demethylation with P450, glucuronidation
    • eliminated primarily in bile, some in urine
  31. What is the MOA or Rifampin?
    inhibits initiation of RNA synthesis (already bound RNA chains are not affected)
  32. What are mechanisms of resistance to Rifampin? (1)
    mutations to RNA polymerase preventing binding
  33. What is important to remember when using Rifampin?
    • must use with another agents or mutants will be selected for rapidly
  34. What are clinical applications of Rifampin? (3)
    • Rhodococcus equi with a macrolide
    • Dogs- MR-Staph with Amikacin, rapidly growing Mycobacteria with Clarithromycin
  35. What are drug interactions (1) and toxicity (1) with Rifampin?
    • induces P450- increase dose of other drug
    • GI side effects in dogs (sterile hepatitis)
  36. What is the rule of thumb for nosocomial infections?
    • infections occurring:
    • after 48hr in hospital admission
    • within 3 days of hospital discharge
    • within 30 days after an operation
  37. What is a superinfection?
    a secondary infection resistant to therapy used to treat the primary infection.
  38. What is Tylosin labelled for?
    • Mycoplasma in chickens, turkey, and swine
    • growth promotion in swine
  39. What is Tylosin frequently used for in dogs?
    sprinkled on food for dogs with chronic small bowel diarrhea and EPI
Card Set
Micro2- Macrolides
vetmed micro2