Carbapenems

Question 1

Cilastatin is

Answer 1

DHP1 inhibitor

Question 2

Carbapenems came from

Answer 2

imipenem

Question 3

Carbapenem base structure

Answer 3

beta-lactam ring fused with a 5 C ring and sulfur is not in the ring

Question 4

CARBapenems

Answer 4

presence of many carbons

Question 5

Modifications at C3 and C4

Answer 5

improve stability, spectrum of activity, and lower epileptogenic potential

Question 6

Imipenem is vulnerable to

Answer 6

renal DHP1 and has epileptogenic potential

Question 7

Meropenem benefits:

Answer 7

stable to renal DHP1 (improved bt 1 beta methyl group on C4), less epileptogenic potential, and increased gram - activity

Question 8

Carbapenem MOA:

Answer 8

bind to and inactivate multiple PBP resulting in inhibition of cell wall synthesis and initiating autolysis

Question 9

Carbapenem spectrum of activity varies depending on

Answer 9

affinity to PBP

Question 10

Doripenem 1/2 life

Answer 10

short

Question 11

Doripenem elimination

Answer 11

renal 70%

Question 12

Imipenem/cilastatin 1/2 life

Answer 12

short

Question 13

Imipenem/cilastatin elimination

Answer 13

renal 70%

Question 14

Meropenem 1/2 life

Answer 14

short

Question 15

Meropenem elimination

Answer 15

renal 70%

Question 16

Carbapenem tissue penetration

Answer 16

peritoneal fluid
urine
lung
bone
CSF dosing is different for meningitis

Question 17

Carbapenem CSF penetration

Answer 17

very low with no inflammation and not the best with inflammation but meropenem would work the best out of all of them

Question 18

Carbapenems are bactericidal/bacteriostatic

Answer 18

bactericidal

Question 19

What PD property is used for carbapenems?

Answer 19

% Time> MIC

Question 20

Carbapenems have the _____ % Time >Mic requirement

Answer 20

shortest

Question 21

What is the % requirement for carbapenems to have bactericidal activity?

Answer 21

40%

Question 22

Carbapenem spectrum coverage

Answer 22

dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE, E. faecalis
dark red: Neisseria, h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeruginosa, acinetobacter
anaerobes: ++ oral and gut
Misc: stable against ESBL and AmpC, activity against mycobacterium, inactive against s. maltophilia

Question 23

Carbapenems do not cover

Answer 23

MRSA/MRSE and e. faecium

Question 24

Common carbapenems include

Answer 24

doripenem, imipenem/cilastatin, meropenem

Question 25

Ertapenem is unique because

Answer 25

it has anionic character that results in decreased penetration into porin channels found in pseudonomas

Question 26

Ertapenem also has

Answer 26

increased protein binding and increased 1/2 life

Question 27

Ertapenem does not cover

Answer 27

acinetobacter, p. aeruginosa, MRSA, enterococcus

Question 28

Ertapenem 1/2 life

Answer 28

medium/long 4 hours

Question 29

Ertapenem elimination

Answer 29

renal

Question 30

Hemodialysis can remove ___% of Ertapenem

Answer 30

30

Question 31

Ertapenem spectrum coverage

Answer 31

dark purple: streptococcus, s. pneumoniae, viridans, MSSA/MSSE dark red: Neisseria, h. influenzae, m. cattarhalis, E. coli, klebsiella, p. mirabilis, Morganella, enterobacter, citrobacter, serratia anaerobe: ++ (oral and gut) Misc: stable against ESBL and AmpC, inactive against S. maltophilia

Question 32

Carbapenem resistance

Answer 32

- stable from hydrolysis from numerous beta lactamases - enterobacteriaceae/acinetobacter inactivate the drug by carbapenem-hydrolyzing enzymes - pseudonomas decreased outer membrane permeability (altered porin channels) and active efflux - mutant or acquired altered PBPs

Question 33

Addition of beta-lactamase inhibitor to carbapenems advantage:

Answer 33

expands coverage

Question 34

Meropenem/vaborbactam advantage:

Answer 34

expanded activity against CRE (KPCs)

Question 35

Vaborbactam does/does not enhance activity against pseudomonas aeruginosa or acinetobacter that are resistant to carbapenems due to efflux or porin mutations

Answer 35

does NOT

Question 36

Imipenem/cilastatin/relebactam advantage:

Answer 36

- expanded activity against CRE (KPCs and some OXA-type) and carbapenem resistant pseudomonas aeruginosa - may have a role in treatment of nontuberculous mycobacterial infections

Question 37

Adverse events related to to carbapenems

Answer 37

``` CNS GI hepatic renal skin hematologic anaphylaxis ```

Question 38

Drug interactions with carbapenems

Answer 38

-effect on valproic acid (loss of seizure control) should consider alternative antibacterial or anticonvulsant -probenecid interferes with tubular secretion of all carbapenems

Question 39

Antipseudomonal Carbapenem indications

Answer 39

- ESBL/AmpC infections - strong propensity for selecting for resistant organisms (increasing incidence of carbapenem-resistant enterobacteriaceae) - should be considered in cefepime or pipercilln/tazobactam resistant gram - bacilli - clinical worsening while receiving extended spectrum penicillin or cephalosporins

Question 40

Ertapenem dosing

Answer 40

QD, eases transition to home

Question 41

Ertapenem indications

Answer 41

stable against ESBL and AmpC beta-lactamases intra-ab infections skin/skin structure infections CA pneumonia UTI pelvic infections surgical prophylaxis in colorectal surgery

Question 42

Antipseudomonal carbapenems include

Answer 42

doripenem, morepenem, imipenem/cilastatin

Question 43

Carbapenem/beta lactamase inhibitor indications

Answer 43

- expanded activity against carbapenem-resistant enterobacteriaceae (CRE) - utilization is driven by susceptibility profile and should be used as definitive therapy

Question 44

Carbapenem/beta lactamase inhibitor drugs are

Answer 44

EXPENSIVE

Question 45

Carbapenems are broad/narrow spectrum

Answer 45

broad