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Resistance mechanisms are either _________ or _________, which are...
- intrinsic: resistance d/t inherent metabolic attributes of the organism
- acquired: resistance d/t acquisition of exogenous genes via mobile DNA elements or mutations
Antimicrobial susceptibility testing is a(n) _________ assessment that attempts to predict __________.
in vitro; in vivo activity
What are the common AST methods?
- broth microdilution
- Kirby-Bauer disk diffusion
Describe broth microdilution testing.
- two fold dilution series of the drug in Muller-Hinton broth
- add a standardized amount of baceria to each tube and incubate
- minimum inhibitory concentration (MIC) for this bacterial isolate is determined
How do you interpret the MIC from broth microdilution testing? (3)
- must know pharmacokinetics of the drug
- the pharmcodynamics of the drug versus different type of bacteria
- and the population distributions of the drug MICs for different bacteria
Describe the Kirby-bauer disc testing method of susceptibility testing.
- disc of antimicrobial on innoculated plate
- measure zone of inhibition in mm, breakpoints outlined
- disc testing is a correlate of MIC
Is one method of susceptibility testing more favorable than the other?
- sometimes MIC testing can inform drug dosage
- slow-growing organisms MUST use MIC testing (broth microdilution) [b/c drug diffuses slowly from disc before organism can grow on agar]
What are the population MIC parameters?
- MIC50 and MIC90
- calculated as percentiles
- MIC90 is a reasonable bar to deciding on empirical therapy
- MIC50 may or may not be normally distributed (bimodal distributions are common)
Describe the general characteristics of the cephalosporin family. (4)
- eliminated via the kidney
- low Vd (distribution is mostly ECF)
- most drugs in this class do not cross the BBB
Cephalosporins work by...
interrupting cell wall function
Describe the spectrum of activity of cephalosporins.
- variable, esp among Enterobacteriacea (some have intrinsic resistance,some have acquired resistance)
- dissemination of transferable resistance genes (beta-lactamase genes) on plasmids
Describe the classification of cephalosporins by generation and the spectrum of each.
- First gen: gram + aerobes and anaerobes, some strains of E. coli, Proteus, Klebsiella
- Second gen: gram + aerobes and anaerobes, gram - aerobes and anaerobes (esp B. fragilis)
- Third gen: Primarily gram - (good against most Enterobactericea), some gram +, [*exception: some of these cross the BBB]
- Fourth gen: similar to third gen, just aerobes, not widely used in vetmed
Name some first gen cephalosporins. (5)
- Oral: cephalexin, cephalothin, cefadroxil
- Parenteral: cefazolin
- intramammary: cefapirin
Name some second gen cephalosporins. (2)
Parenteral: cefoxitin, cefotetan
Name some third gen cephalosporins. (4)
- Parenteral: Ceftazidime, Ceftriaxone (crosses the BBB), ceftiofur
- Oral: cefpodoxime
What are the major important exceptions to the activity of cephalosporins? (3)
- Enterococcus: cephalosporins have no activity against these organisms because intrinsically lack PBP affinity
- Bordatella: oral cephalosporins have no activity against this organism b/c it's impermeable (occasionally parenteral is useful)
- Pseudomonas aeruginosa: intrinsic cephalosporinase production (SOME third gen may work, like ceftazidime)