176: Beta-lactam Antimicrobials

Question 1

What are the 3 groups of beta-lactam antimicrobials?

Answer 1

• penicillins
• cephalosporins
• carbapenems

Question 2

What is the basic structure all beta-lactam antimicrobials share?

essential to their biologic activity

Answer 2

beta-lactam ring

substitutions are made on this ring, e.g., to increase resistance

Question 3

Explain the mechanism of action of beta-lactam antimicrobials

Answer 3

bactericidal
* bind and inhibit the penicillin-binding proteins (PBP)
* PBP = transpeptidases and peptidoglycan-active enzymes
* PBP are needed to catalyze cross-linking of peptidoglycans to build bacterial cell walls

bacteria must be actively growing for beta-lactam to be efficacious

Question 4

What does the susceptibility of bacteria to beta-lactams depend on?

Answer 4

• amount of peptidoglycan in the cell wall
• amount of lipid in the cell wall

Question 5

Explain how beta-lactams’ lipid solubility affects its concentration in different organs

Answer 5

beta-lactams are lipid insoluble and therefore have poor penetration of cell walls and biologic membranes
* low concentration in eyes, testes, prostate, brain

Question 6

how are beta-lactams excreted

Answer 6

mostly excreted in the active form by the kidneys

higher cc in urine than serum

Question 7

How does the cephalosporins’ susceptibility change across 1st, 2nd, 3rd generation?

Answer 7

generally become more gram-negative specific with increasing generation

Question 8

what is the indication of 5th generation cephalosporins?

Answer 8

methicillin-resistant staphylococci

Question 9

What are the 3 main beta-lactamase enzymes?

Answer 9

• penicillinases
• cephalosporinases
• carbapenemases

Question 10

What is ESBL?

Answer 10

extended-spectrum beta-lactamase
* produced by certain gram-negative organisms
* breaks down penicillins and cephalosporins, but not carbapenems

Question 11

what has shown to increase the risk of fecal ESBL-bacteria carriage?

Answer 11

anitmicrobial administration in the last 3 months

Question 12

besides beta-lactamase production, how can bacteria create resistance to beta-lactams? What is a “famous” example for this?

Answer 12

bacteria may change cell wall permeability by changing their penicillin-binding proteins (PBP) in their cell wall
e.g., staphyloccocus gene mecA encoding PBP-2a –> MRSA

Question 13

What is the spectrum of Penicillin G?

Answer 13

• good against gram+ and anerobes, except staphylococcus

Question 14

What are indications for Penicillin G?

Answer 14

streptococcal infections, e.g., necrotizing fasciitis
clostridial infection
actinomycosis

Question 15

How do extended spectrum penicillins compare to Penicillin G in their efficacy?

Answer 15

less active against gram+ and anaerobes
greater efficacy agaisnt gram-

Question 16

Name 2 antipseudomonal penicillins

Answer 16

• Ticarcillin
• Piperacillin

Question 17

Name 2 first generation cephalosporins

Answer 17

• cefazolin
• cephalexin

Question 18

What is the spectrum of first generation cephalosporins?

Answer 18

• high activity against gram+
• moderate activity against gram-
• minimal activity against anaerobes

Question 19

Name a second-generation cephalosporin

Answer 19

cefoxitin

Question 20

How does the efficacy of the second and third cephalosporin generation compare to the first generation?

Answer 20

higher efficacy against gram-

Question 21

Name 3 third generation cephalosporins

Answer 21

• ceftiofur
• cefpodoxime
• cefovecin

Question 22

What is the efficacy of carbapenems against MRSA?

Answer 22

not efficacious

Question 23

What beta-lactam group is efficacious against MRSA?

Answer 23

5th generation cephalosporins

Question 24

Name 2 Carbapenems

Answer 24

• imipenem
• meropenem

Question 25

Are beta-lactams time- or concentration-dependent?

Answer 25

time-dependent