Cell Wall inhibitors Flashcards
What is the mechanism of action of beta-lactam antibiotics?
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.
Why is probenecid given with penicillin?
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)
What is benzathine and what are it’s side affects?
Long acting intramuscular injection of penicillin which are absorbed more slowly but are associated with irritation and local pain.
What is penicillinase (and amidase)?
Enzyme produced by almost all staphylococcal strains and most neisseria. It cleaves the beta-lactam ring and inactivates penicillins.
Name two penicillinase resistant penicillins and explain their mechanism for avoiding inhibition.
What is their antimicrobial spectrum?
(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
Name and describe three beta-lactamases.
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 - .
Name three penicillinase inhibitors. How do they work?
Clavulanate- combined with penicillin, it binds irreversibly to penicillinase allowing penicillin to be an effective drug
Sulbactam and Tazobactam are additional beta-lactamase inhibitors
Which Aminopenicillin is associated with C diff?
Ampicillin
Name two aminopenicillins. Are they penicillinase resistant? What is their antimicrobial spectrum?
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)
Name two antipseudomonals. Are they penicillinase resistant? What is their antimicrobial spectrum?
Ticarcillin and Pipercillin.
NOT penicillinase resistant. but can be combined with clavulanate and tazobactam respectively.
Broad activity against Gram - including pseudomonas
How do penicillin and other beta-lactam cause allergic reaction?
they combine with your proteins to form “hapen protein” stimulating the immune system resulting in productionof specific antibodies to this antigen
What is the monocyclic beta-lactam used if patient is allergic to penicillin?
Monobactum-Aztreonam
effective agianst Gram - including Klebsiella, pseudomonoas, serratia
inactivated by extended spectrum beta-lactamases
How does the antimicrobial spectrum of cephazolins change as you go from first generation to fifth generation?
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
What is the spectrum and what are the complications of Carbepenems? How are they administered? Beta-lactam?
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
How are all beta lactams excreted?
Via the kidneys
What are the two main mechanisms of resistance to beta-lactams?
- Beta-lactamases
2. change in structure of penicillin binding protein
How does Vancomycin’s mechanism of action differ from beta-lactams?
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
What are the side effects of vanco? How are bacteria resistant?
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!
What is Bacitracin’s mech of action? Is it a beta-lactam?
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
Mech of action and spectrum for Polymyxin B?
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
Mech, spectrum, and side effects for Daptomycin are:
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
