Lecture 11 2/22/24 Flashcards
Which antibiotics need to have a certain concentration above MIC to be effective?
-aminoglycosides
-ketolides
Which antibiotics need to have a certain time above MIC to be effective?
-beta-lactams
-cephalosporins
-macrolides
-lincosamides
-sulfonamides
-tetracyclines
-‘amphenicols
Which antibiotics need to have a certain AUC above MIC to be effective?
fluoroquinolones
Which antibiotics are bactericidal?
-beta-lactams
-aminoglycosides
-nitrofurans
-nitroimidazoles
-fluoroquinolones
Which antibiotics are bacteriostatic?
-sulfonamides
-tetracyclines
-macrolides
-chloramphenicol
What is the mechanism of action for beta-lactams?
-inhibit bacterial cell wall synthesis
-prevent cell wall components from cross-linking
Which antibiotics fall into the beta-lactams class?
-penicillins
-aminopenicillins
-antipseudomonal penicillins
-antistaphylococcal penicillins
-cephalosporins
-carbepenems
-monobactems
What are the penicillin-binding proteins?
the bacterial proteins that penicillins target
What are the characteristics of penicillin pharmacokinetics?
-weak acid w/ pKa around 2.7
-mostly ionized in plasma/intestine
-unstable at gastric pH
-low volume of distribution
-generally not orally bioavailable
-renal elimination via glomerular filtration and tubular secretion
-short half-life
-concentrated in urine
What are the characteristics of penicillin G pharmacokinetics?
-not orally bioavailable
-inactivated at low pH
What are the characteristics of procaine penicillin G?
-formulated for IM administration
-absorbed more slowly after IM injection compared to sodium penicillin G
Why is frequent dosing of penicillin G required?
penicillin G is rapidly excreted
Why are slow release formulations useful in the case of beta-lactams?
-beta-lactams have short half-lives
-beta-lactams exhibit time-dependent pharmacodynamic behavior
What is the general rule regarding beta-lactam efficacy?
penicillins are more effective with frequent administration for the same total daily dose
How does efficacy change with time above MIC?
efficacy increases as time above MIC approaches 100% of the dose interval
Why should a longer infusion time be used when infusing beta-lactams?
-longer infusion times allow for more time above MIC
-the concentration reached does not matter as much as the time spent at a concentration above MIC
What are the characteristics of beta-lactamase production as a way to resist beta-lactams?
-major mechanism of resistance
-enzymes capable of hydrolyzing the cyclic amide bond
-can be inherent or acquired
-can inactivate penicillins, cephalosporins, or both
What is inherent beta-lactamase resistance?
gram neg. bacteria inherently express low levels of chromosomally-mediated beta-lactamases within the periplasmic space
What are some examples of gram neg. bacteria with inherent beta-lactamases?
-Klebsiella spp.
-Pseudomonas spp.
-Bacteroides fragilis
What is acquired beta-lactamase resistance?
gram pos. bacteria secrete beta-lactamases extracellularly as inducible exoenzymes that are plasmid mediated
Which species is known for acquired beta-lactamase resistance?
Staphylococcus aureus
What are beta-lactamase inhibitors?
inhibitors that bind irreversibly to beta-lactamases and improve the efficacy of the beta-lactam with which they are combined
What is an example of a beta-lactamase inhibitor?
clavulanate
What must occur in order for antibiotics to reach the cell wall in gram neg. bacteria?
they must penetrate the outer membrane layer via a porin protein
Why are gram pos. bacteria more susceptible to beta-lactams than gram neg. bacteria?
it is easier to reach the site of action in gram pos. bacteria due to the lack of outer membrane
Which type of resistance is seen in MRSA, MRSP, and Enterococcus faecium?
production of PBPs with low affinity for beta-lactams
What are L-forms?
bacterial variants that lack a cell wall
What are some of the challenges involved with penicillin compliance?
-anaphylaxis in veterinary staff/owners administering the drug
-injections sting
What are the characteristics of penicillin adverse effects and toxicity?
-acute toxicity is minimal
-diarrhea may occur with oral doses
-procaine reaction when given IV in horses
Which animals often experience diarrheal reactions to penicillin?
horses and other animals with a large cecum
What are the main examples of gram pos. bacteria that are susceptible to penicillin G?
-all beta-hemolytic Streptococci
-Actinomyces spp.
-Clostridium spp.
What are the main examples of bacteria that are resistant to penicillin G?
-Enterobacteriaeceae
-Bacteroides fragilis
-Staphylococcus spp.
-Pseudomonas aeruginosa
Which bacteria are treated with penicillin G?
-most gram pos. bacteria
-Haemophilus spp.
-Pasteurella spp.
-many anaerobes
What are the advantages of penicillin G?
-potent
-bactericidal activity
-wide margin of safety
What are the disadvantages of penicillin G?
-must be given as injection
-narrow-spectrum
-widespread resistance
-low ability to cross biological membranes
What is the spectrum for penicillin G?
-high susceptibility of gram pos. aerobes and anaerobes
-some susceptibility of gram neg. aerobes and anaerobes
-no susceptibility of gram pos. or neg. facultative anaerobes
What are the characteristics of aminopenicillins?
-addition of side chains
-extended gram pos. and gram neg. spectrum
-increased acid stability
What is the spectrum of aminopenicillins?
-high susceptibility of gram pos. aerobes and anaerobes
-decent susceptibility of gram neg. aerobes
-some susceptibility of gram neg. anaerobes
-no susceptibility of gram pos. or neg. FAs
What are potentiated penicillins?
penicillins mixed with a beta-lactamase inhibitor
What is the spectrum of potentiated penicillins?
-high susceptibility of gram pos. aerobes and anaerobes
-decent susceptibility of gram pos. FAs and gram neg. aerobes, anaerobes, and FAs
What are the characteristics of antistaphylococcal penicillins?
-increased resistance to Staph. beta-lactamase
-oral and parenteral formulations available
What is the spectrum of antistaphylococcal penicillins?
-some susceptibility of gram pos. aerobes and anaerobes
-high susceptibility of gram. pos. FAs/Staph.
-no susceptibility of any gram neg.
What are the characteristics of antipseudomonal penicillins?
-increased penetration in gram neg. bacteria
-increased resistance to beta-lactamases
-multiplicity of PBP targets
-expensive
-parenterally administered
-used in serious gram neg. infections
What is the spectrum of antipseudomonal penicillins?
-decent susceptibility of gram pos. aerobes and anaerobes
-no susceptibility of gram pos. FAs
-some susceptibility of gram neg. aerobes and anaerobes
-high susceptibility of gram neg. FAs
