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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)
- [GET OTHER ONE]
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How do you measure IgG in foals to test for FPT? (2)
- radial immunodiffusion
- Zinc sulfate turbidity test
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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
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What is the most likely gram negative organism isolated from a bacteremic FPT foal's blood?
E. coli
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What are the most common isolated from bacteremic foals' blood cultures? (4)
- Strep zooepidemicus
- E coli
- Actinobacillus spp
- Salmonella enterica
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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
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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)
- NO COVERAGE FOR ANAEROBES
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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)
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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
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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
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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
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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
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What is the ideal dosing regime for aminoglycosides?
- dose high, dose infrequently
- maximum Cmax:MIC, minimum trough level
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Aminoglycosides are __________ and rapidly _________.
concentration- dependent (Cmax: MICâ„ 10); bactericidal
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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)
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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)
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Aminoglycosides have decreased activity in _______ environments, such as...
acidic; abscesses, necrotic debris (not good for these cases)
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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
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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)
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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
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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)
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What are the relative nephrotoxicities of aminoglycosides?
Neomycin> Gentamicin>>> Amikacin> Tobramycin
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What are the relative vestibular toxicities of aminoglycosides?
Gentamicin> Neomycin> Amikacin= Tobramycin
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What are the relative cochlear toxicities of aminoglycosides?
Neomycin> Amikacin= Gentamicin> Tobramycin
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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
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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
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What are differentials for equine bacterial diarrhea? (5)
- Salmonella enterica
- Clostridium difficile
- Clostridium perfringens
- Lawsonia intracellularis
- Neorickettsia risticii
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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
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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
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How do you diagnose C. perf diarrhea in horses? (2)
- culture
- toxin type isolate by PCR
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How do you diagnose C. diff diarrhea in horses? (2)
- Culture
- ELISA on feces for toxin
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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
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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
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Describe Neorickettsia infection in dogs.
- Salmon poisoning- Neorickettsia helminthoeca
- not common in this part of the country (seen out west)
- Treated with tetracycline
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