Antimicrobials - Cell Wall Synthesis Inhibitors

Question 1

Name the major classifications of cell wall synthesis inhibitors

Answer 1

• penicillins
• cephalosporins
• carbapenem
• monobactam
• vancomycin

Question 2

Contrast the mechanism of action of lactams vs. vancomycin

Answer 2

Lactams: inhibit crosslinking/transpeptidation by interacting with PBP

Vanco: inhibit polymerization/transglycosylation by interacting with D-ala-D-ala muramul pentapeptide

Question 3

What are the two most common PBPs and what binds to each?

Answer 3

PBP 2b: penicillins, 1st gen cephalosporins

PBP 2x: all other cephalosporins, carbapenems, monobactams

Polymorphic alterations in these proteins by microbes can create resistance to lactam drugs

Question 4

What are 2 ways to protect the lactam ring from hydrolysis?

Answer 4

1) place large aromatic groups to sterically hinder the access of penicillinase
2) combine with a suicide inhibitor

Question 5

How do lactam induced allergies usually manifest?

Answer 5

• anaphylaxis, maculopapular skin eruption
• maculopapular rash is due to antigenic reaction with IgM and shows no cross reactivity
• distinguish these from commonly seen nausea/vomiting, which isn’t an allergy but a side effect

Question 6

If a patient is allergic to penicillin, which other drugs can you expect that they will or will not be allergic to?

Answer 6

Cross-allergenicity with cephalosporins

No cross-allergenicity with aztreonam (a monobactam)

Question 7

What is the bacterial spectrum of penicillin?

Answer 7

Strep species and oral anaerobes

Question 8

What is the bacterial spectrum of penicillinase resistant penicillins (oxacillin, dicloxicillin), and what is their equivalent cephalosporin in terms of microbial coverage?

Answer 8

Strep species and MSSA

1st gen cephalosporins (cefazolin, cephalexin)

Question 9

What is the bacterial spectrum of aminopenicillins (ampicillin, amoxicillin) + cavulanate and what is their equivalent cephalosporin in terms of microbial coverage?

Answer 9

Strep species, H. flu, all anaerobes, MSSA

2nd gen cephalosporins (cefotetan, cefaclor, cefuroxime)

Question 10

What is the bacterial spectrum of extended spectrum penicillins (piperacillin)? What if you add tazobactam? Throw in their equivalent cephalosporins

Answer 10

ESP: Strep species, G- rods
3rd gen cephalosporins (ceftriaxone, cefotaxime, cefdinir, cefixime

+ tazo: Strep species, G- rods, all anaerobes, MSSA
4th gen cephalosporins (cefepime)

Question 11

What is the bacterial spectrum of carbapenem (imipenem)?

Answer 11

Broad G+ cocci and G- rods

Not MRSA

Question 12

What is the bacterial spectrum of monobactam (aztreonam)?

Answer 12

G- only

Question 13

What are two mechanism microbes can utilize to gain vancomycin resistance?

Answer 13

1) remodeling the peptidoglycan

2) thickening the peptidoglycan

Question 14

What is the main clinical indication for use of vancomycin?

Answer 14

MRSA

Can also be used for

• Staph epidermidis
• ampicillin-resistant enterococcus
• pneumococcal meningitis
• metronidazole-resistant C. difficile

Question 15

What are the potential side effects of vancomycin?

Answer 15

• Red man syndrome: flushing, tachycardia, hypotension (vasodilatory, occurs when drug is given too quickly)
• Allergy
• Ototoxicity
• Nephrotoxicity