Bacterial Cell Wall and Beta Lactam Antibiotics Flashcards
Color of gram (+) bacteria under gram stain?
dark purple
Color of gram (-) bacteria under gram stain?
light pink
How do gram (+) and gram (-) bacteria differ?
differ in the structures of their cell walls
How can some drugs get into gram (-) bacteria?
through the porins in the outer membrane
Is the peptidoglycan layer thicker in gram (-) or gram (+) bacteria?
much thicker in gram (+) bacteria
How many membranes do gram (+) bacteria have?
one membrane
How many membranes do gram (-) bacteria have?
two membranes - inner and an outer membrane
What enzyme cross-links the peptidoglycan strands?
transpeptidase
Describe the beta-lactam antibiotic mechanism of action.
inhibition of transpeptidases that “glue” the peptidoglycan strands together by cross-linking
Why do the bacterial transpeptidases not catalyze reactions with host cell proteins?
the bacterial substrate contains unnatural D-Ala amino acid residues that are not found in the host cell proteins
Name three ways resistance to beta-lactam antibiotics can develop.
- decreased cellular uptake of the drug
- mutation of the penicillin-bindin gproteins to decrease their affinity for penicillins
- the presence of an efflux pump that pumps the antibiotic out of the cell
Most common mechanism of resistance to beta-lactam antibiotics
induction or elaboration of bacterial beta-lactamases
Describe the reaction that beta-lactamaes catalyze.
the hydrolysis of the beta-lactam moiety
The allergenicity of beta-lactam antibiotics results from?
the drug acting as a hapten, acylates host cell proteins, which raise antibodies and cause an allergic reaction
Can a person who has demonstrated an allergy to one penicillin be given another penicillin?
No, because cross-sensitivity is common.
What should be kept away from penicillin solutions?
heavy metal ions (they catalyze penicillin degradation reactions)
Which routes are penicillins rapidly excreted by?
the renal or biliary routes
10% of renal excretion of penicillins is by?
glomerular filtration
90% of renal excretion of penicillins is by?
tubular secretion
What happens when probenecid is administered along with penicillin?
The anionic penicillin competes with the anion probenecid for the tubular secretion mechanism in the kidneys - causes an increase in the half life of penicillin
Benzylpenicillin (Penicillin G) antimicrobial spectrum:
Gram (+) cocci + Neisseria gonorrhoeae and Haemophilus influenza [both gram (-)]
Is Benzylpenicillin (Penicillin G) beta-lactamase sensitive?
yes
Precautions when using Penicillin G (Benzylpenicillin)
Pen G should be used with caution in individuals with histories of significant allergies and/or asthma
What drug is the drug of choice for treatment of more infections than any other antibiotic?
Pen G
Is Methicillin beta-lactamase sensitive?
No.
Why must methicillin be administered by injection?
it is unstable to acid in the stomach
What’s the antibiotic spectrum of methicillin?
narrow. It is primarily for treatment of beta-lactamase-producing Staphylococcus aureus
Why is MRSA resistant to Methacillin?
because of a mutation in the penicillin-binding protein (transpeptidase) - methicillin resistance gene (mecA)
What kind of antibiotic is Cephapirin?
a cephalosporin antibiotic
What does cepharpirin have fused to the beta-lactam instead of a five-membered ring?
It has a six-membered sulfur-containing ring fused to the beta-lactam
Cephalosporins that have what are inactivated by the hydrolysis of the acetate by host esterases?
cephalosporins that have an acetate in the 3-position
Carbapenems are carbon analogs of what?
penicillins
Besides reacting with penicillin-binding proteins, what else does imipenem react with?
Imipenem reacts with and inhibits beta-lactamases
What is imipenem hydrolyzed by?
renal dehydropeptidase-1
How can you overcome the hydrolyzation of impenem by renal dehydropeptidase-1?
co-administration of the dehydropeptidase-1 inhibitor, cilastatin
cilastatin
renal dehydropeptidase-1 inhibitor
What has a broader spectrum of Abx activity than any other antibiotic presently available in the US?
the combination of imipenem with cilastatin
What is imipenem with cilastatin active against?
gram (+) and gram (-) bacteria
Why is imipenem use typically restricted?
to avoid widespread bacterial resistance
What is the combination of imipenem with cilastatin used to treat?
serious infections of the gut, GU tract, bone, skin and endocardium
Antibiotic spectrum on Aztreonam?
focuses almost completely on Gram (-) bacteria
Aztreonam disodium is used mainly in the treatment of what?
severe infections with gram (-) bacteria, especially those by penicillin-resistant organisms acquired in hospitals
Cross allergenicity with penicillins and cephalosporins has not been reported except for?
ceftazidimine - has an identical sidechain
