Lecture 15 3/22/24

Question 1

What is the antimicrobial mechanism of sulfonamides?

Answer 1

-analogue of PABA
-competitively inhibits synthesis of dihydrofolic acid from PABA

Question 2

What is the antimicrobial mechanism of diaminopyrimidines?

Answer 2

interference with folic acid synthesis

Question 3

What are the general characteristics of sulfonamides?

Answer 3

-bacteriostatic by self
-bactericidal when combined with diaminopyrimidines
-less effective in presence of necrotic debris
-poorly active in anaerobic environments, even when culture/susceptibility testing may indicate otherwise

Question 4

What is the spectrum of activity for sulfonamides?

Answer 4

-decent susceptibility of aerobic and FA bacteria
-no susceptibility of anaerobic bacteria

Question 5

Which bacteria are exhibiting resistance to sulfonamides?

Answer 5

-Pseudomonas
-Enterococcus
-Bacteroides
-Mycoplasma
-MRSA
-MRSP

Question 6

What are the characteristics of sulfonamide pharmacokinetics?

Answer 6

-well absorbed orally
-good distribution to most tissues, including CNS and prostate

Question 7

What are the characteristics of sulfonamide elimination?

Answer 7

-hepatic acetylation and renal elimination
-reach high urine concentrations
-longer half-lives than trimethoprim

Question 8

What are the characteristics of trimethoprim elimination?

Answer 8

-hepatic oxidation and conjugation
-short half-life

Question 9

How often can sulfonamides be dosed, based on their half lives?

Answer 9

every 12 hours

Question 10

What are the clinical applications of sulfonamides in horses?

Answer 10

-Salmonella enteritis
-strep. infections
-protozoal encephalomyelitis
-one of the few safe/effective oral drugs

Question 11

What are the clinical applications of sulfonamides in small animals?

Answer 11

-soft tissue infections
-prostatic infections
-CNS infections
-eye infections
-UTI
-coccidiosis

Question 12

What are the characteristics of sulfonamide toxicity/adverse effects?

Answer 12

-combo. typically has wide safety margin
-crystalluria and hematuria
-thrombocytopenia and anemia
-hypersensitivity reactions, mainly in dobermans
-keratoconjunctivitis sicca

Question 13

Which class of animals can sulfonamides NOT be used in?

Answer 13

prohibited in lactating dairy cattle

Question 14

Which group of animals are fluoroquinolones NOT able to be used in?

Answer 14

banned from EXTRALABEL use in food animals

Question 15

Which fluoroquinolones are approved for use in vet med?

Answer 15

-enrofloxacin
-danofloxacin
-orbifloxacin
-difloxacin
-marbofloxacin
-pradofloxacin

Question 16

What is the mechanism of action for fluoroquinolones?

Answer 16

-inhibition of topoisomerase II and IV
-inhibits DNA replication and results in cell death

Question 17

What is the spectrum of 2nd gen fluoroquinolones?

Answer 17

-high susceptibility of gram neg. aerobes and FAs
-decent susceptibility of gram pos. FAs
-some susceptibility of gram pos. aerobes EXCEPT Enterococcus
-no susceptibility of anaerobes

Question 18

Which bacteria exhibit resistance to fluoroquinolones?

Answer 18

-Enterobacter
-E. coli
-Pseudomonas aeruginosa
-Proteus spp.
-MRSP

Question 19

How do the second gen. fluoroquinolones differ from the third gen. fluoroquinolones in terms of spectrum?

Answer 19

-second gen. has broad gram neg. and narrow gram pos. spectrum
-third gen. has broad gram neg. and gram pos. spectrum, with some activity against anaerobes

Question 20

How does ciprofloxacin differ from enrofloxacin and marbofloxacin?

Answer 20

-cipro is more active for gram-neg. bacilli
-enro is more active against Staph.
-marbofloxacin is an intermediate

Question 21

What are the characteristics of fluoroquinolone pharmacokinetics?

Answer 21

-lipid soluble
-generally well absorbed
-high bioavailability
-cations can decrease bioavailability
-low pH at activity site can impact MIC
-purulent material has no affect on activity
-widely distributed

Question 22

What are the characteristics of fluoroquinolone elimination?

Answer 22

-renal elimination
-enrofloxacin partially metabolized in liver
-difloxacin primarily eliminated in feces
-highly concentrated in urine

Question 23

Why is it important that fluoroquinolones are concentration dependent?

Answer 23

-optimal killing occurs when the fCmax/MIC ratio is 10-12
-for gram pos., want an fAUC/MIC ratio of at least 40 for optimal killing
-for gram neg., want an fAUC/MIC ratio of at least 100

Question 24

What is mutant prevention concentration?

Answer 24

higher concentration where bacteria are not likely to survive to become resistant

Question 25

What are the clinical uses of fluoroquinolones?

Answer 25

-broad gram neg. spectrum w/ wide dist.
-UTIs
-skin and soft tissue infections
-prostatitis by gram neg. bact
-intracellular infections
-resp. disease and colibacillosis in pigs
-resp. disease in cattle

Question 26

Why are fluoroquinolones a good choice in small animals?

Answer 26

-less likely to cause clostridial overgrowth
-do not affect the anaerobes that compete with Clostridium spp.

Question 27

How can fluoroquinolones be used in reptiles?

Answer 27

effective against gram neg. enteric bacteria such as Salmonella

Question 28

Why are fluoroquinolones not approved for use in poultry?

Answer 28

treatment with fluoroquinolones lead to the evolution of resistant Campylobacter strains, which is a human pathogen

Question 29

What are the characteristics of fluoroquinolone toxicity?

Answer 29

-overall safe
-arthropathy and erosion of joint cartilage
-retinal damage in cats in high doses
-CNS stimulation/tremors/seizures

Question 30

Why is pradofloxacin NOT used in dogs?

Answer 30

shown to cause bone marrow depression