Micro1- Aminoglycosides

  1. What are the 2 mechanisms of beta-lactam resistance in staphylococci?
    • coag + organisms: most all encode a penicillinase (only potentiated penicillins will work against them)
  2. How do you measure IgG in foals to test for FPT? (2)
    • radial immunodiffusion
    • Zinc sulfate turbidity test
  3. What is an important aspect of FPT work-up?
    • blood cultures (b/c sepsis is what you're worried about here)
    • surgical prep of venipuncture site b/c culture is susceptible to skin surface contamination
  4. What is the most likely gram negative organism isolated from a bacteremic FPT foal's blood?
    E. coli
  5. What are the most common isolated from bacteremic foals' blood cultures? (4)
    • Strep zooepidemicus
    • E coli
    • Actinobacillus spp
    • Salmonella enterica
  6. How do you handle an FPT case in a foal? (4)
    • collect blood culture and send out
    • initiate empirical therapy- IV antibiotics (3rd gen ceph- ceftiofur, ceftazidime; dual therapy with aminoglycoside indicated)
    • aggressive supportive care
    • adjust antibiotics based on blood culture results
  7. What is the spectrum of aminoglycosides?
    • cidal against aerobic and facultative gram -
    • some gram +, especially staphs
    • Gram -: Enterobacteriacae, Pseudomonas
    • Gram +: Staph, Enterococci (only when combined with a beta-lactam)
  8. What drugs are aminoglycosides? (5) How are they administered?
    • [ALL PARENTERAL or topical]
    • Gentamicin
    • Amikacin
    • Tobramycin (rarely used b/c too expensive)
    • Neomycin (not used much anymore)- exception- administered orally for hepatic encephalopathy in dogs
    • Streptomycin (not used much anymore)
  9. Aminoglycosides have no ___________, except in the following case...
    • oral absorption
    • Neomycin is given orally for dogs with hepatic encephalopathy because we want the drug to stay in the GI tract
  10. What are the urease producing bacteria in the large intestine?
    • Proteus
    • Enterbacter
    • these bugs produce NH3; we want to kill these microbes in cases of hepatic encephalopathy--> give oral neomycin
  11. What is the MOA of aminoglycosides?
    O2-dependent entry into bacterial cell wall (ie. not effective against anaerobes; also, facultatives don't die if there is no O2 present)--> binds to 30S ribosome, causing misreading of mRNA--> protein synthesis is disrupted--> cell membrane is damaged--> drug uptake increases
  12. Describe the pharmacokinetic properties of aminoglycosides?
    • poor lipid solubility
    • distribution to ECF (low Vd)
    • no intracellular accumulation
    • does not cross BBB
    • entirely eliminated by kidneys
  13. What is the ideal dosing regime for aminoglycosides?
    • dose high, dose infrequently
    • maximum Cmax:MIC, minimum trough level
  14. Aminoglycosides are __________ and rapidly _________.
    concentration- dependent (Cmax: MIC≄ 10); bactericidal
  15. Describe the post-antibiotic effect of aminoglycosides.
    • continued kill despite dropping MIC (even though conc-dependent)
    • Higher Cmax--> more post-antibiotic effect
    • this allows us to dose SID (or even longer)
  16. Describe "adaptive resistance" of aminoglycosides.
    • temporary decline in drug uptake (kinda of like saturation with the drug)
    • therefore, we have to wait long enough between doses for bacteria to become susceptible again (about 16+ hours)
  17. Aminoglycosides have decreased activity in _______ environments, such as...
    acidic; abscesses, necrotic debris (not good for these cases)
  18. What are some aminoglycoside toxicities? WHat is the mechanism?
    • Ototoxic: cochlear, vestibular
    • Nephrotoxic: tubular necrosis
    • b/c they're so positively charged, they line up on the brush border of these types of cells--> with normal turnover of the cell membrane, all of this drug is getting endocytosed into the cell--> eventually, these things coalesce, rupture, and kill the cell
  19. What are risk factors for aminoglycoside toxicity? (2)
    • decreased GFR d/t dehydration, renal dz
    • given concurrently with other nephrotoxic drugs, such as NSAIDs (d/t constriction of afferent arteriole)
  20. How do you minimize the risk for aminoglycoside toxicity?
    • take a blood sample and measure serum aminoglycoside level (at 24hour mark- look for 24-hr trough level) to determine exactly how often to re-dose
    • Goal is to:
    • maximize Cmax (to maximize PAE)
    • minimize trough
  21. How do you monitor aminoglycoside therapy? (2)
    • take blood samples to measure 24-hr trough level
    • look for urinary casts (cellular or granular)
    • BUN is not acceptable (this is a late indicator of big time damage)
  22. What are the relative nephrotoxicities of aminoglycosides?
    Neomycin> Gentamicin>>> Amikacin> Tobramycin
  23. What are the relative vestibular toxicities of aminoglycosides?
    Gentamicin> Neomycin> Amikacin= Tobramycin
  24. What are the relative cochlear toxicities of aminoglycosides?
    Neomycin> Amikacin= Gentamicin> Tobramycin
  25. How do aminoglycosides induce neuromuscular blockade?
    • decrease presynaptic Ca uptake--> decreased Ach release
    • this can lead to respiratory arrest
    • risk factors for this include: low blood Ca, Mg
    • Neomycin> Amikacin> Gentamicin> Tobramycin
  26. Describe the mechanism of acquired aminoglycoside resistance.
    • Plasmid-encoded enzymes in Gram + and Gram -
    • Not all enzymes inactivate all drugs- this is why susceptibility testing is extremely important
  27. What are differentials for equine bacterial diarrhea? (5)
    • Salmonella enterica
    • Clostridium difficile
    • Clostridium perfringens
    • Lawsonia intracellularis
    • Neorickettsia risticii
  28. What are you major differentials for a foal wtih diarrhea? (4)
    • Foal heat diarrhea (6 days after birth)
    • Salmonella enterica
    • C. difficile Type C (Type A is always cultured...not significant)
    • C. perf
  29. How do you diagnose Salmonella enterica diarrhea in a horse? (2 options)
    • fecal culture with enrichment- 5 negative sequential cultures
    • real-time PCR- fast, but no susceptibility data
  30. How do you diagnose C. perf diarrhea in horses? (2)
    • culture
    • toxin type isolate by PCR
  31. How do you diagnose C. diff diarrhea in horses? (2)
    • Culture
    • ELISA on feces for toxin
  32. Describe Lawsonia organism and how it is diagnosed (2 options) for diarrhea in horses.
    • obligate intracellular organism (ie. YOU CANNOT CULTURE IT)
    • PCR on feces or serology IFA
  33. Describe Neorickettsia organism and how it is diagnosed (2 options) for diarrhea in horses.
    • obligate intracellular (cannot culture!!!!!)
    • PCR on feces or serology IFA
    • common in Ohio!!!! spring and summer- moreso in adult horses
    • Treated with Tetracycline
  34. Describe Neorickettsia infection in dogs.
    • Salmon poisoning- Neorickettsia helminthoeca
    • not common in this part of the country (seen out west)
    • Treated with tetracycline
Card Set
Micro1- Aminoglycosides
vetmed micro1