Carbapenems and Monobactams

Question 1

What was the first carbapenem to come out (in late 1980s)?

Answer 1

imipenem (primaxin)

Question 2

What is the root drug for all the carbapenems?

Answer 2

thienamycin

Question 3

What are the four carbapenems?

Answer 3

imipenem, meropenem, ertapenem, doripenem

Question 4

What do metalloenzymes utilize?

Answer 4

zinc

Question 5

What are two beta-lactamases that have been observed to give resistance to carbapenems?

Answer 5

production of metalloenzymes, production of non-metalloenzymes

Question 6

What is an example of an “old school” drug (that is highly nephrotoxic) that we might have to use if carbapenem treatment fails?

Answer 6

polymixin-B

Question 7

What is the problem with using carbapenems as first-line agents for everything?

Answer 7

they are potent beta-lactamase inducers, so if resistance develops against them nothing else below their level (ie penicillins, cephalosporins, etc) will work either (better to use the least potent effective drug)

Question 8

What are two situations where it might be necessary to use carbapenems?

Answer 8

Acinetobacter infections, presence of ESBLs (extended-spectrum beta lactamases)

Question 9

What is the difference in the carbapenem structure and the penicillin structure?

Answer 9

carbapenems have an additional carbon instead of a sulfur in their five-membered ring

Question 10

Why was it necessary to add cilastatin to thienamycin in imipenem?

Answer 10

because thienamycin by itself if hydrolyzed in the kidney to an inactive metabolite that is toxic; adding cilastatin blocks hydrolysis (restores antibiotic function, prevents renal toxicity)

Question 11

Which carbapenem has the highest incidence of seizures (is most epileptogenic)?

Answer 11

imipenem

Question 12

Are beta lactams concentration dependent or time dependent?

Answer 12

time dependent

Question 13

Why is extended infusion often considered for carbapenems?

Answer 13

because they have short half-lives, so extended infusion improves their time above the MIC (imp because time-dependent drugs)

Question 14

What is the only carbapenem that doesn’t cover pseudomonas?

Answer 14

ertapenem

Question 15

What organisms does ertapenem (invanz) have good activity against?

Answer 15

gram positives (MSSA, etc.), enterobacteriaceae, anaerobes

Question 16

Why is ertapenem a good choice for intra-abdominal infection treatment but a bad choic for Intensive Care hospital infections?

Answer 16

good for intra-abdominal because has anaerobic activity, bad for intensive care because has no pseudomonas activity

Question 17

What is the typical carbapenem extended infusion time?

Answer 17

4 hours

Question 18

What organisms does doripenem, imipenem, and meropenem have good activity against?

Answer 18

gram positive organisms (except MRSA), enterobacteriaceae, pseudomonas, anaerobes

Question 19

What side chain is present in aztreonam (monbactam)?

Answer 19

oxyimino

Question 20

What is the main advantage of aztreonam (azactam)?

Answer 20

it can be used safely (99% of the time) in people with penicillin allergies

Question 21

The monobactam aztreonam has a similar spectrum of activity as ________, but is not nephrotoxic.

Answer 21

aminoglycosides

Question 22

Why do you most always need to combine aztreonam with other drug therapies?

Answer 22

because it has a very narrow spectrum of action

Question 23

What organisms does aztreonam have good activity against?

Answer 23

gram negative aerobes (enterobacteriaceae), pseudomonas (but resistance a big problem)