B-Lactam antibiotics

Question 1

What is mechanism of action of B-lactam antibiotics?

Answer 1

B-lactam antibiotics acetylate the transpeptidase Serine residue which inactivates the enzyme & inhibits peptidoglycan cross-linking

Question 2

What is a major resistance mechanism to B-lactam antibiotics?

Answer 2

activation or elaboration of B-lactamases (enzyme) which catalyze the hydrolysis (inactivation, irreversible reaction) of the B-lactam moiety in B-lactam antibiotics

Question 3

What penicillin derivates are more protein bound? What does that affect?

Answer 3

most protein bound - Dicloxacillin (>90%)
Benzylpenicillin (~45-68%)
least protein bound - Ampicillin(25-30%)
-more protein bound = less bioavailability

Question 4

What is the method of excretion for penicillins?

Answer 4

largely metabolized through the kidneys

Question 5

What add-on is used to prolong the half-life of penicillin?

Answer 5

Probenecid

Question 6

What is the resistance gene associated with MRSA?

Answer 6

mecA
PBP2A -penicillin binding protein it codes for

Question 7

What medications are B-lactamase resistant?

Answer 7

Oxacillin (injection only), Dicloxacillin (oral)

Question 8

What medications are B-lactamase sensitive?

Answer 8

Ampicillin, amoxicillin (better oral absorption), Piperacillin (IV), Penicillin V, Penicillin G

Question 9

What are the B-lactamase inhibitors?

Answer 9

Clavulanate + Amoxicillin = Augmentin
Tazobactam + Piperacillin = Zosyn
Sulbactam + Ampicillin = Unasyn
Avibactam + Ceftazidine = Avycaz
-acetylate the serine hydroxyl group in B-Lactamase active site

Question 10

What makes a B-lactam antibiotic less susceptible to hydrolysis?

Answer 10

increased electronegativity of the side chains reduces the nucleophilicity and stabilizes it in acidic conditions (more favorable for oral)

Question 11

What penicillins are broad-spectrum?

Answer 11

Ampicillin (more favorable for Gram negative organisms); Amoxicillin
-due to the charged amino group can access porins in gram negative organisms
Piperacillin

Question 12

What penicillins are narrow-spectrum?

Answer 12

Pencillin G & V (gram postive)

Question 13

What is the main difference between penicillins and cephalosporins?

Answer 13

cephalosporins are 6 membered rings attached to the B-lactams
-reaction is usually carried out with leaving group ‘X’ that causes ring opening

Question 14

What is a first generation cephalosporin and what activity does it have?

Answer 14

Cefazolin (IV), Cephalexin (oral)
-gram + organisms

Question 15

What makes a cephalosporin orally vs parenterally active?

Answer 15

orally active cephalosporins have unreactive side chains at C-3 group

Question 16

What is a second generation cephalosporin and what activity does it have?

Answer 16

Cefuroxime (IV and oral)
gram + organisms
-some gram - organisms

Question 17

What is a third generation cephalosporin and what activity does it have?

Answer 17

Ceftazidime (IV), Cefixime (oral)
gram - organisms

Question 18

What is a fourth generation cephalosporin and what activity does it have?

Answer 18

Cefepime (IV)
gram - organisms
more active against gram + organisms than 3rd generation

Question 19

What is a fifth generation cephalosporin and what activity does it have?

Answer 19

Ceftatroline
-gram +/- organisms
-active against MRSA (able to inhibit the mecA gene)