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What is the MOA of beta-lactams?
inhibition of peptidoglycan and cell wall synthesis
What is the mechanism of resistance to beta-lactams?
- 1. beta lactamase enzymes
- 2. decreased penetration (porin changes)
- 3. alteration in penicillin-binding proteins
How is methicillin resistance from beta lactase acquired?
-by the insertion of a horizontally transferred DNA element called SCCmec
-The mega gene encodes PBP2a (a beta-lactam insensitive PBP) which continually synthesizes new cell wall peptidoglycan, even when usual PBP's are inhibited.
What is the only effective beta-lactam antibiotic against MRSA?
What are beta lactase inhibitors?
"suicide" inhibitors that bind to and inactivate beta-lactase enzymes
What are ESBLs?
ESBL's are extended spectrum beta-lactamases that are plasmid-mediated enzymes that inactivate a wide range of beta-lactams, and also confer resistance to many other antimicrobials
ex. of resistance = quinilones, tetracyclines, TMP/SMX
Name primary examples of of beta-lactamase inhibitors.
- -clavulanic acid
Describe the absorption profile of beta-lactams.
- -variable PO (oral) absorption
- -generally should be taken 1 hour before or 2 hours after meals
Describe the distribution profile of beta-lactams.
- -wide distribution to tissues and fluids
- -variable CNS penetration; 3rd generation cephalosporins are widely used in meningitis
Describe the metabolism and excretion profile of beta-lactams.
- -primarily eliminated really
- -nafcillin, oxacillin, and ceftriaxone are eliminated hepatic ally
- -most have very short half lives
Name the "natural penicillins".
Penicillin G and Penicillin VK
What organisms are Penicillin G and Penicillin K active against?
Streptococcus spp., Neisseria miningitis, Pasturella multocida, Treponema pallidum, Listeria monocytogenes
NO ACTIVITY against staphylococcus app. and most gram negs
Are penicillin G and VK effective against anaerobes?
Yes. Above the diaphragm
What is penicillin G and VK the drug of choice for?
infections caused by Group A Strep (progenies) and Treponema palladium (syphilis)