Cephalosporins Gen 5

Question 1

Which 5th gen cephalosporin is only available in Canada?

Answer 1

ceftobiprole

Question 2

Which two types of infections are typically used to test safety/efficacy in new drug trials?

Answer 2

upper respiratory infections, skin/skin structure infections

Question 3

Why are 5th generation cephalosporins active against MRSA?

Answer 3

structurally engineered to bind to PBP2a of MRSA

Question 4

Besides MRSA, what other organisms are 5th generation cephalosporins active against that none of the 1-4 gen cephalosporins are?

Answer 4

enterococci

Question 5

The gram-negative activity of 5th generation cephalosporins is similar to what 3rd generation cephalosporin?

Answer 5

ceftriaxone

Question 6

What is the 5th generation cephalosporin available in the US?

Answer 6

ceftaroline fosamil (teflaro)

Question 7

When was ceftaroline approved?

Answer 7

2010

Question 8

Ceftaroline is FDA approved to treat what?

Answer 8

complicated skin/soft tissue infections (MRSA), community-acquired pneumonia

Question 9

What organisms does ceftaroline have good activity against?

Answer 9

MSSA, MRSA, streptococci, enteric GNRs

Question 10

What organisms does ceftaroline have moderate activity against?

Answer 10

acinetobacter, enterococcus faecalis

Question 11

What organisms does ceftaroline have poor activity against?

Answer 11

pseudomonas aeruginosa, enterococcus faecium, anaerobes

Question 12

When is PBP2a formed in staphylococci?

Answer 12

when the “mecA” gene is expressed in the chromosome

Question 13

What are the four molecular beta lactamase classes based on protein sequence?

Answer 13

A, B, C, D

Question 14

Which molecular beta lactamase classes based on protein sequence hydrolyze substrate by forming an acyl enzyme through an active serine site?

Answer 14

classes A, C, D

Question 15

How does molecular beta lactamase class B (based on protein sequence) hydrolyze substrate?

Answer 15

hydrolyze metalloenzymes that utilize zinc (ion)

Question 16

What is the problem with classifying beta lactamases based on protein sequence (even though it is non-controversial)?

Answer 16

not helpful from a clinical perspective

Question 17

What is the other way to classify beta lactamases besides protein sequence?

Answer 17

according to ability to hydrolyze different classes of beta-lactams

Question 18

What is the advantage of classifying beta lactamases based on what drugs they hydrolyze (even though it is controversial)?

Answer 18

it is clinically useful

Question 19

What are five types of beta-lactamases?

Answer 19

penicillinases (s. aureus), cephalosporinases, broad spectrum, extended spectrum beta lactamases, carbapenemases

Question 20

What does the KPC-2 enzyme stand for and why is it problematic?

Answer 20

Klebsiella pneumoniae carbapenemase 2; problem because there is nothing today that is effective against organism with this enzyme

Question 21

Group 1, Class C beta lactamases generally affect…

Answer 21

cephalosporins

Question 22

Group 2a, Class A beta lactamases generally affect ________ and contain what organism?

Answer 22

penicillins and Staphylococcus aureus

Question 23

Group 2be, Class A beta lactamases generally affect…

Answer 23

extended-spectrum beta lactams (3rd gen cephalosporins), monobactams

Question 24

Group 2f, Class A, and Group 3a, Class B beta lactamases affect…

Answer 24

carbapenems

Question 25

In which group/class is the KPC-2 enzyme found?

Answer 25

Group 2f, Class A

Question 26

Group 2b, Class A beta lactamases generally affect...

Answer 26

broad spectrum beta lactams

Question 27

Group 2br, Class A beta lactamases affect...

Answer 27

penicillins

Question 28

Group 2e, Class A beta lactamases affect...

Answer 28

extended-spectrum beta lactams (3rd gen cephalosporins)

Question 29

Which organisms usually naturally produce AmpC enzymes (think SPACE)?

Answer 29

serratia, pseudomonas, acinetobacter, citrobacter, enterobacter

Question 30

What is the purpose of the AmpC gene?

Answer 30

repressor gene that keeps beta-lactamase production in check (stops it or keeps it low when antibiotic not present)

Question 31

What is de-repression?

Answer 31

when the AmpC gene turns off when antibiotic present (so beta lactamase made) and turns back on when antibiotic not present

Question 32

What is stable de-repression?

Answer 32

when the AmpC gene doesn't turn back on when the antibiotic not present (beta lactamase production remains high)

Question 33

What was a likely reason the MICs for SPACE organisms (that made AmpC) continued to go up despite ongoing treatment?

Answer 33

de-repression, or stable de-repression (worse)

Question 34

Extened-spectrum beta-lactamases mediate resistance to beta lactams that contain what?

Answer 34

oxyimino side chains (3rd gen ceph, oxyimino-monobactams)

Question 35

Extended-spectrum beta lactamses do not affect which beta lactams?

Answer 35

cefamycins (cefoxitin, cefotetan), carbapenems

Question 36

If an extended-spectrum beta lactamase is confirmed present, which beta lactams should automatically be reported as resistant?

Answer 36

penicillins, cephalosporins, aztreonam

Question 37

What are six known extended-spectrum beta lactamase producing organisms?

Answer 37

Klebsiella pneumoniae, klebsiella oxytoca, escherichia coli, pseudomonas aeruginosa, salmonella, proteus mirabilis

Question 38

Why are cefamycins not a good choice for treating extended-spectrum beta lactamase infections (even though ESBLs don't affect them?

Answer 38

they are intrinsically not very active against many ESBL-producing organisms

Question 39

What should be avoided in order to minimize the development of ESBL-producing organisms?

Answer 39

using extended spectrum cephalosporins (3rd gen) for empiric treatment

Question 40

What are three empiric therapy options besides extended-spectrum cephalosporins that don't facilitate the development of ESBL-producing organisms?

Answer 40

extended-spectrum penicillins, pencillins plus beta lactamase inhibitors, cefepime (4th gen ceph)

Question 41

Chromosomal-mediated AmpC beta lactamases confer resistance to what?

Answer 41

cefamycins

Question 42

Group 2b, Class A beta lactamases (affect broad-spectrum beta lactams) have what three enzymes?

Answer 42

TEM-1, TEM-2, SHV-1

Question 43

Are Group 1, Class C, Group 2br, Class A, and Group 3a, Class B beta lactamases inhibited by clavulanic acid?

Answer 43

no

Question 44

What beta lactamase group contains AmpC enzymes?

Answer 44

Group 1, class C