Cell Wall inhibitors

Question 1

What is the mechanism of action of beta-lactam antibiotics?

Answer 1

They bind to Penicillin Binding Proteins which are transpepsidases that catalyze the terminal reactions in bacterial wall sysnthesis. This inhibits crosslinking of peptidoglycan by transpepsidases.

Question 2

Why is probenecid given with penicillin?

Answer 2

Probenecid impairs the renal secretion of weak acids and allows penicillin to stay in the blood longer (penicillin has a short half life of about 30 minutes)

Question 3

What is benzathine and what are it’s side affects?

Answer 3

Long acting intramuscular injection of penicillin which are absorbed more slowly but are associated with irritation and local pain.

Question 4

What is penicillinase (and amidase)?

Answer 4

Enzyme produced by almost all staphylococcal strains and most neisseria. It cleaves the beta-lactam ring and inactivates penicillins.

Question 5

Name two penicillinase resistant penicillins and explain their mechanism for avoiding inhibition.

What is their antimicrobial spectrum?

Answer 5

(originally Methicillin which is no longer used) now Naficillin and Dicloxacillin.

they utilize the same mechanism as penicillins but have larger R groups making them resistant to penicillinase

very narrow spectrum

can still cause same hypersensitivity reactions

Question 6

Name and describe three beta-lactamases.

Answer 6

Penicillinase-more common in staphylocci and prefer penicillin structure

Cephalosporinases- prefer cephalosporin structure

Extended spectrum beta-lactamases (NDM-1)- recognize most beta-latam and are more common in Gram - .

Question 7

Name three penicillinase inhibitors. How do they work?

Answer 7

Clavulanate- combined with penicillin, it binds irreversibly to penicillinase allowing penicillin to be an effective drug

Sulbactam and Tazobactam are additional beta-lactamase inhibitors

Question 8

Which Aminopenicillin is associated with C diff?

Answer 8

Ampicillin

Question 9

Name two aminopenicillins. Are they penicillinase resistant? What is their antimicrobial spectrum?

Answer 9

Ampicillin and Amoxicillin.

NOT penicillinase resistant. But can be combined with Sulbactam and Clavulanate respectively

Wider spectrum

includes some Gram - like H influenza, E coli, Listeria, Salmonella

Ampicillin is associated with pseudomembranous colitis (C diff)

Question 10

Name two antipseudomonals. Are they penicillinase resistant? What is their antimicrobial spectrum?

Answer 10

Ticarcillin and Pipercillin.

NOT penicillinase resistant. but can be combined with clavulanate and tazobactam respectively.

Broad activity against Gram - including pseudomonas

Question 11

How do penicillin and other beta-lactam cause allergic reaction?

Answer 11

they combine with your proteins to form “hapen protein” stimulating the immune system resulting in productionof specific antibodies to this antigen

Question 12

What is the monocyclic beta-lactam used if patient is allergic to penicillin?

Answer 12

Monobactum-Aztreonam

effective agianst Gram - including Klebsiella, pseudomonoas, serratia

inactivated by extended spectrum beta-lactamases

Question 13

How does the antimicrobial spectrum of cephazolins change as you go from first generation to fifth generation?

Answer 13

1st- Gram + cocci

• used for surgical prophylaxis
• does NOT cross blood brain barrier

2nd-more Gram - activity and less Gram +

• used immediately prior to surgery to prevent infection
• doesn’t cross BBB well
• can inhibit Vit K production (bleeding risk)
• don’t take with EtOH!

3rd- used for streptococci and more serious Gram - infections that are resistant to other beta-lactams

• CAN cross blood brain barrier (used for meningitis)
• strong association with C diff

4th- 1st gen + 3rd gen = broadest spectrum against Gram +, and Gram - including pseudomas
-empiric therapy

5th-NEW! engineered to bind to penicillin binding protein 2a present in MRSA that has low binding affinity for other beta-lactams
-used for skin and soft tissue infections

Question 14

What is the spectrum and what are the complications of Carbepenems? How are they administered? Beta-lactam?

Answer 14

Broad spectrum but MRSA is resistant

cleavage of beta-lactam ring by dehydropeptidase is nephrotoxic; countered by the addition of cilastatin

can only be given parenterally

yes, it’s a beta lactam with low susceptibility to beta-lactamases but now Klebsiella pneumoniae have carbapenemase

Question 15

How are all beta lactams excreted?

Answer 15

Via the kidneys

Question 16

What are the two main mechanisms of resistance to beta-lactams?

Answer 16

1. Beta-lactamases

2. change in structure of penicillin binding protein

Question 17

How does Vancomycin’s mechanism of action differ from beta-lactams?

Answer 17

inhibits transglycosylase instead of transpepsidase (actually binds the polypeptide tails but inhibits peptidoglycan synthesis)

• Gram +, especially MRSA, C diff
• oral vanco is poorly absorbed (in the case of C diff, thats what you want)

-bactericidal just like all the beta-lactams

Question 18

What are the side effects of vanco? How are bacteria resistant?

Answer 18

red man syndrome-hypersensitivity
nephrotoxicity- excreted by kidneys just like beta-lactams

Enterococci change their AA tail so vanco can’t bind

***some staphylococci have have learned this, now there are MRSA+VRSA…yikes!

Question 19

What is Bacitracin’s mech of action? Is it a beta-lactam?

Answer 19

prevents dephosphorylation of bactoprenol carrier needed in elongation of peptidoglygan cell wall.

not a beta lactam

ususally topical/dermatologic, weak evidence of benefit

nephrotoxic when given IM

resistance: rare

Question 20

Mech of action and spectrum for Polymyxin B?

Answer 20

binds to LPS (from Diebel lectures), creates hole in cell MEMBRANE

spectrum: multidrug resistant Gram - bacilli including pseudomonas aeruginosa and Klebsiella pneumoniae

nephrotoxic

infrequent and slow to develop resistance

Question 21

Mech, spectrum, and side effects for Daptomycin are:

Answer 21

aggregates in cell MEMBRANE letting K+ out and leading to depolarization.

only Gram +, vanco resistant, MRSA

change in charge on surface of cell membrane can lead to resistance