Oxazolidinones

Question 1

Linezolid structure

Answer 1

incorporation of piperazine moiety into basic structure; has 3 rings: hexene with F, 5 membered with N and O inside ring, and 6 membered with N and O inside ring

Question 2

Linezolid has increased activity due to

Answer 2

hydroxyacetyl group to heterocyclic nitrogen on 5 membered ring and fluorine

Question 3

Linezolid MOA

Answer 3

acts as a protein synthesis inhibitor by binding to the V-domain of the 23S RNA component of the 50S ribosomal unit

Question 4

Linezolid is bactericidal/bacteriostatic

Answer 4

bacteriostatic

Question 5

Linezolid spectrum coverage

Answer 5

GRAM + ONLY
dark purple: streptococcus, s. pnuemoniae, viridans, MSSA, MRSA, e, faecalis, e. faecium, VRE
anaerobes: gram +
Misc: mycobacterium tuberculosis, other mycobacterium, nocardia, actinomycetes

Question 6

Linezolid oral absorption

Answer 6

100% IV:PO

Question 7

Linezolid 1/2 life

Answer 7

5 hours so long

Question 8

Linezolid elimination

Answer 8

30-40% renal

Question 9

Linezolid PK/PD parameters

Answer 9

T>MIC, AUC:MIC

Question 10

Linezolid needs/doesnt need renal adjustment

Answer 10

does not

Question 11

Linezolid CSF penetration

Answer 11

good!

Question 12

Linezolid dosing

Answer 12

600mg IV or PO q12 hours

Question 13

Linezolid adverse effects

Answer 13

hematologic toxicities 
thrombocytopenia (mostly with treatment > 2 weeks)
anemia
weekly CBC
optic neuritis (prolonged use)
peripheral neuropathy (prolonged use)

Question 14

Linezolid drug interactions

Answer 14

does not interact with CYP450s

Question 15

Linezolid is metabolized by

Answer 15

oxidation

Question 16

Linezolid is a weak, non-selective _____

Answer 16

monoamine oxidase inhibitor

Question 17

What is commonly seen with Linezolid?

Answer 17

serotonin syndrome due to excess serotonin in the CNS

Question 18

signs/symptoms of serotonin syndrome

Answer 18

mental status change
agitation
myoclonus
hyperreflexia
diaphoresis
shivering
tremor
diarrhea
incoordination
fever

Question 19

When does serotonin syndrome develop

Answer 19

within 6 hours of initiation of medication of a change in medication that increases serotonin levels

Question 20

There is no _____ SSRI

Answer 20

safe

Question 21

How long does micromedex suggest to wait after discontinuing Effexor or citalopram before taking Linezolid?

Answer 21

14 days; 5 weeks with prozac

Question 22

____ outweighs ___ of initiating treatment for infection

Answer 22

benefit; risks

Question 23

Linezolid resistance

Answer 23

mutation of 23S rRNA
horizontal acquisition of chloramphenicol-florfenicol resistance gene (cfr)
alterations in ribosomal proteins

Question 24

Tedizolid is a

Answer 24

novel oxazolidinone prodrug

Question 25

Tedizolid maintains activity against

Answer 25

cfr positive strains

Question 26

Tedizolid MOA

Answer 26

inhibition of bacterial synthesis by binding to 23S ribosomal RNA of the 50S subunit this prevents the formation of 70S ribosomal initiation complex therefor preventing translation of proteins

Question 27

Tedizolid is bactericidal/bacteriostatic

Answer 27

bacteriostatic

Question 28

Tedizolid oral absorption

Answer 28

very good 91% IV:PO

Question 29

Tedizolid 1/2 life

Answer 29

12 hours very long

Question 30

Tedizolid elimination

Answer 30

18% renal, 3% unchanged

Question 31

PK/PD for Tedizolid

Answer 31

AUC:MIC

Question 32

Tedizolid does/does not need renal adjustment

Answer 32

does not

Question 33

Tedizolid dosing IV

Answer 33

QD; 1 hour infusion time x 6d

Question 34

Tedizolid dosing PO

Answer 34

QD x 6d

Question 35

Tedizolid spectrum

Answer 35

more potent than linezolid against all staphylococci, streptococci, enterococci, MRSA, VISA, VRSA has activity against linezolid resistant MRSA

Question 36

Tedizolid drug interactions

Answer 36

low potential for drug interactions with CYPs - weaker reversible inhibition of MAOIs compared to linezolid - lower potential to interact with serotonergic agents, MAOIs, and tyramine containing foods

Question 37

How is Tedizolid excreted from the liver?

Answer 37

as an inactive, non-circulating sulfate

Question 38

Tedizolid adverse effects

Answer 38

peripheral neuropathy and optic nerve disorders | less thrombocytopenia than linezolid

Question 39

Tedizolid resistance

Answer 39

mutations in chromosomal genes encoding 23S rRNA or ribosomal proteins

Question 40

Tedizolid retains activity against

Answer 40

vancomycin-resistant enterococci and linezolid resistant MRSA that have cfr gene

Question 41

Tedizolid indications

Answer 41

``` bacteremia pneumonia osteomyelitis skin and soft tissue infections meningitis ```

Question 42

Cleavage of which of the following features improves the susceptibility of Tedizolid against resistant bacteria? a. fluorination in ring B b. hydroxymethyl group c. d-ring d. phosphate group

Answer 42

d

Question 43

Does Tedizolid have lower risk of serotonin syndrome compared to linezolid?

Answer 43

possibly, phase III studies excluded patients on serotonergic agents

Question 44

Which of the following adverse reactions would you be most concerned with a patient taking linezolid 600mg po q12hr for 5 days? a. thrombocytopenia b. optic neuritis c. peripheral neuropathy d. none

Answer 44

d because thrombocytopenia usually after 2 weeks and peripheral neuropathy and optic neuritis usually after 28 days