Lecture 15 3/22/24 Flashcards
What is the antimicrobial mechanism of sulfonamides?
-analogue of PABA
-competitively inhibits synthesis of dihydrofolic acid from PABA
What is the antimicrobial mechanism of diaminopyrimidines?
interference with folic acid synthesis
What are the general characteristics of sulfonamides?
-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
What is the spectrum of activity for sulfonamides?
-decent susceptibility of aerobic and FA bacteria
-no susceptibility of anaerobic bacteria
Which bacteria are exhibiting resistance to sulfonamides?
-Pseudomonas
-Enterococcus
-Bacteroides
-Mycoplasma
-MRSA
-MRSP
What are the characteristics of sulfonamide pharmacokinetics?
-well absorbed orally
-good distribution to most tissues, including CNS and prostate
What are the characteristics of sulfonamide elimination?
-hepatic acetylation and renal elimination
-reach high urine concentrations
-longer half-lives than trimethoprim
What are the characteristics of trimethoprim elimination?
-hepatic oxidation and conjugation
-short half-life
How often can sulfonamides be dosed, based on their half lives?
every 12 hours
What are the clinical applications of sulfonamides in horses?
-Salmonella enteritis
-strep. infections
-protozoal encephalomyelitis
-one of the few safe/effective oral drugs
What are the clinical applications of sulfonamides in small animals?
-soft tissue infections
-prostatic infections
-CNS infections
-eye infections
-UTI
-coccidiosis
What are the characteristics of sulfonamide toxicity/adverse effects?
-combo. typically has wide safety margin
-crystalluria and hematuria
-thrombocytopenia and anemia
-hypersensitivity reactions, mainly in dobermans
-keratoconjunctivitis sicca
Which class of animals can sulfonamides NOT be used in?
prohibited in lactating dairy cattle
Which group of animals are fluoroquinolones NOT able to be used in?
banned from EXTRALABEL use in food animals
Which fluoroquinolones are approved for use in vet med?
-enrofloxacin
-danofloxacin
-orbifloxacin
-difloxacin
-marbofloxacin
-pradofloxacin
What is the mechanism of action for fluoroquinolones?
-inhibition of topoisomerase II and IV
-inhibits DNA replication and results in cell death
What is the spectrum of 2nd gen fluoroquinolones?
-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
Which bacteria exhibit resistance to fluoroquinolones?
-Enterobacter
-E. coli
-Pseudomonas aeruginosa
-Proteus spp.
-MRSP
How do the second gen. fluoroquinolones differ from the third gen. fluoroquinolones in terms of spectrum?
-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
How does ciprofloxacin differ from enrofloxacin and marbofloxacin?
-cipro is more active for gram-neg. bacilli
-enro is more active against Staph.
-marbofloxacin is an intermediate
What are the characteristics of fluoroquinolone pharmacokinetics?
-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
What are the characteristics of fluoroquinolone elimination?
-renal elimination
-enrofloxacin partially metabolized in liver
-difloxacin primarily eliminated in feces
-highly concentrated in urine
Why is it important that fluoroquinolones are concentration dependent?
-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
What is mutant prevention concentration?
higher concentration where bacteria are not likely to survive to become resistant
