Beta-Lactams Flashcards
what does ADME stand for?
absorption/route
distribution
metabolism
excretion
what are the mechanisms of action for beta-lactams?
inhibit cell wall synthesis
bactericidal
how do beta-lactams inhibit cell wall synthesis?
bind to penicillin binding proteins and reduce cross linking of the peptidoglycan cell wall
what is the most significant mechanism of acquired resistance?
production of beta-lactamases: acquired chromosomally or via plasmids/transposons
what are the mechanisms of resistance to beta lactams?
production of beta-lactamases
alteration of penicillin-binding protein
crypticity (drug property)
altered PBP
what is crypticity?
a drug property that contributes to resistance
ability to reach the site of action in gram negative bacteria
the mecA gene codes for a different PBP- PBP2a that ______________________________________________
does not allow binding by any beta-lactam
what type of mutation is the mecA gene that codes for a different PBP - PBP2a?
chromosomal
true/false: time above MIC is more important that how far above the MIC is reached for beta lactams
true
what is the most important adverse effect of beta lactams?
diarrhea/colic/disruption of fermentation
caution with use in hind gut fermenters
penicillin G is _____-labile
acid
who should you not use penicillin G in?
guinea pigs
caution in rabbits and chinchillas
what are the two main formulations of penicillin G?
crystalline
procain penicillin G: not IV
does penicillin G work on E coli?
no
does penicillin work on gram positives or gram negatives in general?
gram positives
what are some microbes that penicillin G works well for?
Streptococcus
anaerobes
what is a gram negative microbe that penicillin G works for?
Leptospirosis
what does increased crypticity of broad spectrum penicillins allow?
better penetration of gram-negative bacteria
can broad spectrum penicillins be given orally?
yes- acid stable
amoxicillin more bioavailable that ampicillin and is recommended for oral therapy (dogs and cats)
what is Polyflex?
ampicillin trihydrate
what is important about extended spectrum penicillins (with gram negatives)?
further increased crypticity and able to bind altered penicillin binding proteins
significant gram negative activity extending to Pseudomonas
which pathogens can extended spectrum penicillins work against?
E. coli
Streptococcus
anaerobe
Leptospirosis
Pseudomonas
what is done to potentiated penicillins?
penicillinase inhibitor is added to the formulation to “release” the penicillin: clavulanic acid, sulbactam
potentiated penicillins only work in those bacteria resistant by virtue of __________________, not with altered penicillin binding protein
penicillinase
how effective is amoxicillin-clavulanate against the four quadrants, and one more?
E. colo in urine, maybe not in tissue
Staphylococcus: ++
Streptococcus: +
anaerobe: +
Bacteroides fragilis: +
do amoxicillin-clavulanate or piperacillin-tazobactam work against Rickettsia or Mycoplasma?
no
what drug is effective against Leptospirosis and Pseudomonas?
piperacillin-tazobactam
what is the structural feature of beta lactams that is a target for drug resistance?
beta lactam ring
what is the distribution of beta lactams?
mostly extracellular
third generation cephalosporins and carbapenems are an exception to limited distribution and penetrate all tissue (including blood brain barrier)
what is the metabolism of beta lactams?
limited
how are beta lactams excreted?
renal filtration and excretion
concentrate in urine which can help their effectiveness with UTIs
how are beta lactams bactericidal?
create osmotic imbalance between hypertonic bacterial interior and isotonic exterior: cell lysis
how do beta lactams inhibit cell wall synthesis?
bind to penicillin binding proteins and reduce cross linking of the petidoglycan wall
how does altered PBP contribute to resistance of beta lactams?
mecA gene codes for a different PBP: PBP2a
PBP2a does not allow binding of any beta lactam
what type of mutation is the mecA gene?
chromosomal
what does the mecA gene mutation imply resistance to?
almost all beta lactams including carbapenems
why are there different targets for necessary time above MIC with beta lactams?
depending on drug and agent
due to post-antibiotic effect
what is added to beta lactams to increase their effect (broad and extended spectrums)?
beta lactamase inhibitor
can you give procain penicillin IV?
no
what is the spectrum of Penicillin G with the 4 quadrants?
E coli: -
Staphylococcus: *
Streptococcus: +
anaerobe: +
what are some broad spectrum penicillins?
aminopenicillins: ampicillin and amoxicillin
is amoxicillin or ampicillin more bioavailable and recommended for oral therapy?
amoxicillin
how can ampicillin trihydrate be given?
IM or SQ
what is the efficacy of ampicillin and amoxicillin against the four quadrants?
E coli: +/-
Staphylococcus: *
Streptococcus: +
anaerobe: +
what is one pathogen that ampicillin and amoxicillin are effective against that is not in the four quadrants?
Leptospirosis
what is the efficacy of piperacillin (extended spectrum penicillins) against the four quadrants?
E coli: ++
Staphylococcus: *
Streptococcus: +
anaerobe: +
what are the potentiateed penicillin formulations?
oral amoxicillin + clavulanic acid: clavamox or augmentin (human)
injectable ampicillin + sulbactam: unasyn (human)
