Cephalosporins Gen 5 Flashcards
Which 5th gen cephalosporin is only available in Canada?
ceftobiprole
Which two types of infections are typically used to test safety/efficacy in new drug trials?
upper respiratory infections, skin/skin structure infections
Why are 5th generation cephalosporins active against MRSA?
structurally engineered to bind to PBP2a of MRSA
Besides MRSA, what other organisms are 5th generation cephalosporins active against that none of the 1-4 gen cephalosporins are?
enterococci
The gram-negative activity of 5th generation cephalosporins is similar to what 3rd generation cephalosporin?
ceftriaxone
What is the 5th generation cephalosporin available in the US?
ceftaroline fosamil (teflaro)
When was ceftaroline approved?
2010
Ceftaroline is FDA approved to treat what?
complicated skin/soft tissue infections (MRSA), community-acquired pneumonia
What organisms does ceftaroline have good activity against?
MSSA, MRSA, streptococci, enteric GNRs
What organisms does ceftaroline have moderate activity against?
acinetobacter, enterococcus faecalis
What organisms does ceftaroline have poor activity against?
pseudomonas aeruginosa, enterococcus faecium, anaerobes
When is PBP2a formed in staphylococci?
when the “mecA” gene is expressed in the chromosome
What are the four molecular beta lactamase classes based on protein sequence?
A, B, C, D
Which molecular beta lactamase classes based on protein sequence hydrolyze substrate by forming an acyl enzyme through an active serine site?
classes A, C, D
How does molecular beta lactamase class B (based on protein sequence) hydrolyze substrate?
hydrolyze metalloenzymes that utilize zinc (ion)
What is the problem with classifying beta lactamases based on protein sequence (even though it is non-controversial)?
not helpful from a clinical perspective
What is the other way to classify beta lactamases besides protein sequence?
according to ability to hydrolyze different classes of beta-lactams
What is the advantage of classifying beta lactamases based on what drugs they hydrolyze (even though it is controversial)?
it is clinically useful
What are five types of beta-lactamases?
penicillinases (s. aureus), cephalosporinases, broad spectrum, extended spectrum beta lactamases, carbapenemases
What does the KPC-2 enzyme stand for and why is it problematic?
Klebsiella pneumoniae carbapenemase 2; problem because there is nothing today that is effective against organism with this enzyme
Group 1, Class C beta lactamases generally affect…
cephalosporins
Group 2a, Class A beta lactamases generally affect ________ and contain what organism?
penicillins and Staphylococcus aureus
Group 2be, Class A beta lactamases generally affect…
extended-spectrum beta lactams (3rd gen cephalosporins), monobactams
Group 2f, Class A, and Group 3a, Class B beta lactamases affect…
carbapenems
In which group/class is the KPC-2 enzyme found?
Group 2f, Class A
Group 2b, Class A beta lactamases generally affect…
broad spectrum beta lactams
Group 2br, Class A beta lactamases affect…
penicillins
Group 2e, Class A beta lactamases affect…
extended-spectrum beta lactams (3rd gen cephalosporins)
Which organisms usually naturally produce AmpC enzymes (think SPACE)?
serratia, pseudomonas, acinetobacter, citrobacter, enterobacter
What is the purpose of the AmpC gene?
repressor gene that keeps beta-lactamase production in check (stops it or keeps it low when antibiotic not present)
What is de-repression?
when the AmpC gene turns off when antibiotic present (so beta lactamase made) and turns back on when antibiotic not present
What is stable de-repression?
when the AmpC gene doesn’t turn back on when the antibiotic not present (beta lactamase production remains high)
What was a likely reason the MICs for SPACE organisms (that made AmpC) continued to go up despite ongoing treatment?
de-repression, or stable de-repression (worse)
Extened-spectrum beta-lactamases mediate resistance to beta lactams that contain what?
oxyimino side chains (3rd gen ceph, oxyimino-monobactams)
Extended-spectrum beta lactamses do not affect which beta lactams?
cefamycins (cefoxitin, cefotetan), carbapenems
If an extended-spectrum beta lactamase is confirmed present, which beta lactams should automatically be reported as resistant?
penicillins, cephalosporins, aztreonam
What are six known extended-spectrum beta lactamase producing organisms?
Klebsiella pneumoniae, klebsiella oxytoca, escherichia coli, pseudomonas aeruginosa, salmonella, proteus mirabilis
Why are cefamycins not a good choice for treating extended-spectrum beta lactamase infections (even though ESBLs don’t affect them?
they are intrinsically not very active against many ESBL-producing organisms
What should be avoided in order to minimize the development of ESBL-producing organisms?
using extended spectrum cephalosporins (3rd gen) for empiric treatment
What are three empiric therapy options besides extended-spectrum cephalosporins that don’t facilitate the development of ESBL-producing organisms?
extended-spectrum penicillins, pencillins plus beta lactamase inhibitors, cefepime (4th gen ceph)
Chromosomal-mediated AmpC beta lactamases confer resistance to what?
cefamycins
Group 2b, Class A beta lactamases (affect broad-spectrum beta lactams) have what three enzymes?
TEM-1, TEM-2, SHV-1
Are Group 1, Class C, Group 2br, Class A, and Group 3a, Class B beta lactamases inhibited by clavulanic acid?
no
What beta lactamase group contains AmpC enzymes?
Group 1, class C
