Antibiotics Against Cell Wall Synthesis Flashcards
(43 cards)
broad spectrum vs extended spectrum
broad spectrum: work against both Gram+ and Gram- bacteria
extended spectrum: selectivity is broadened by chemical modification
why don’t larger drugs typically work on Gram- bacteria?
outer lipid membrane of Gram- bacteria is relatively impervious - transport of drugs through transmembrane pores favores small hydrophilic drugs
in the peptidoglycan layer of bacteria:
______ enzymes join the sugars that make polysaccharide chains
and
______ enzymes join the sugar-linked peptides to x-link polysaccharide chains
Transglycosylase enzymes join the sugars that make polysaccharide chains
and
Transpeptidase enzymes join the sugar-linked peptides to crosslink polysaccharide chains
Penicillin mimics _____, the last 2 amino acids of the peptide-bridge precursor of peptidoglycan layer
Penicillin mimics D-Ala-D-Ala and is picked up by transpeptidase, but penicillin has beta-lactam ring at core (inhibits enzyme action)
[note that D refers to stereochemistry - D amino acids, which are only in bacteria, not humans - we only have L amino acids]
how do beta-lactamase proteins work to confer resistance to penicillins?
beta-lactamases act similarly to transpeptidases (target of penicillin), but hydrolyze serine-lactam linkage
hydrolyzed beta-lactam has no therapeutic value
beta-lactamases and transpeptidases belong to class of proteins that share ability to bind penicillins (PBPs - penicillin binding proteins)
how do beta-lactamase inhibitors work and how are they used?
do not have antibacterial activity - combined with beta-lactam antibiotics (penicillin) to extend their half-lives
inhibitors bind beta-lactamases covalently and inactive irreversibly
Avibactam
broad spectrum beta-lactamase inhibitor (does not contain beta-lactam core)
beta-lactamases have 3 classes: A, C, and D
Avibactam works on class A, C, and some D enzymes
what are the 3 classes of penicillin and a major example of each?
- common (penicillin G): acid labile, beta-lactamase susceptible
- anti-staphylococcal penicillin (cloxacillin): acid stable, beta-lactamase resistant
- extended-spectrum penicillins (amoxicillin): acid stable, inactivated by lactamases - require combination with lactamase inhibitors
CAP: cloxacillin, amoxicillin, penicillin
uses of cloxacillin vs amoxicillin vs penicillin G
penicillin G: Gram+/Gram- cocci and non-beta-lactamase producing anaerobes
cloxacillin (anti-staphylococcal): beta-lactamase-producing Staph and penicillin-susceptible strains of Strep. and pneumococci
amoxicillin (extended-spectrum): greater activity against Gram- bacteria (penetrate outer membrane)
what is cloxacillin, an anti-staphylococcal penicillin, suitable for? what is it not suitable for?
cloxacillin: acid stable, beta-lactamase resistant
suitable: beta-lactamase producing Staph, penicillin-susceptible strep. and pneumococci
NOT suitable: enterococci, anaerobic bacteria, Gram- cocci and rods
which of these types of penicillin have greater activity against Gram- bacteria?
a. penicillin G
b. cloxacillin
c. amoxicillin
c. amoxicillin: extended-spectrum penicillin, can penetrate outer membrane of Gram- bacteria
however, inactivated by lactamases, so require combination with beta-lactamase inhibitors (ex: amoxicillin + clavulanate = Augmentin)
provide the following for penicillins:
a. route of administration
b. route of elimination
c. adverse reactions
route of administration: oral, IV, IM
route of elimination: rapid active secretion via kidney —> use with probenecid which competitively inhibits secretion to increase steady state
adverse reactions: diarrhea, nausea, rash, urticaria (but very non-toxic), Candida superinfection
how can the steady state of penicillin be increased, given that it is rapidly secreted by the kidney?
take with probenecid which competitively inhibits secretion
take PRObenecid with Penicillin to PROactively extend its half life
by what mechanism does MRSA acquire penicillin resistance?
mutation in primary penicillin binding protein (PBP) - transpeptidase - which reduces affinity
name a first, second, third, and fourth generation cephalosporin (beta-lactam antibiotics)
1st: cefazolin: restricted to surgical prophylaxis, does not penetrate CNS
2nd: cefuroxime axetil
3rd: ceftriaxone: some cross BBB, no allergic cross-reactivity with penicillin, extend Gram- activity at expense of Gram+
4th: cefepime: true broad spectrum drug, penetrates CNS (also no cross-reactivity with penicillin), can be used for MRSA
when they played the Z[VI]OLIN I took my AXE and got in the X[Z]ONE and was at my P[R]IME
which of these cephalosporins is effective against inducible beta-lactamase-production but not constitutive beta-lactamase producing strains?
a. cefazolin
b. cefuroxime axetil
c. ceftriaxone
d. cefepime
c. ceftriaxone: 3rd gen, extends Gram- activity at expense of Gram+, some cross BBB, no allergic cross-reactivity with penicillin
which of these cephalosporins is restricted to surgical prophylaxis?
a. cefazolin
b. cefuroxime axetil
c. ceftriaxone
d. cefepime
a. cefazolin: 1st gen, broad spectrum but better for Gram+, does not penetrate CNS
which of these cephalosporins is a true broad spectrum drug that can penetrate the CNS?
a. cefazolin
b. cefuroxime axetil
c. ceftriaxone
d. cefepime
d. cefepime: 4th gen, more resistant to chromosomal beta-lactamases, no cross-reactivity with penicillin
for cephalosporins, provide the following:
a. route of administration
b. route of elimination
c. adverse reactions
route of administration: oral, IV
route of elimination: kidney
adverse reactions: hypersensitivity reactions (anaphylaxis, fever, rash, nephritis, granulocytopenia, hemolytic anemia), Candida superinfection
cefiderocol
beta-lactamase resistant cephalosporin with higher permeability to Gram- but no activity against Gram+
contains side chain that mimics bacterial siderophores (chelate iron to facilitate import) —> allows drug to enter like a trojan horse
administered via injection for complicated UTI
ceftaroline
cephalosporin with activity against MRSA
high/broad affinity towards transpeptidases, works on both Gram+ and Gram-
effective against skin infections, administered via IV
use of monobactams (such as aztreonam)
beta-lactam antibiotic, relatively resistant to beta-lactamases
great for Gram- rods, NO activity towards Gram+
given via IV and excreted rapidly, no cross-reactivity with penicillin
What are carbapenems and what are they used for?
beta-lactam antibiotics, broad spectrum, used for mixed infections
can penetrate CNS, renal clearance, given via IV
may be cross-sensitivity in patients with penicillin allergy
contrast Imipenem and Meropenem, two carbapenems (beta-lactam antibiotics, broad spectrum)
imipenem: inactivated by dehydropeptidases in renal tubules —> give with Cilastatin, an inhibitor of renal dehydropeptidases
meropenem: resistant to modification by renal dehydropeptidases
