Oxazolidones (Linezolid and Tedizolid)

Question 1

MOA

Answer 1

Bind to the 50S subunit near the surface of the 30S subunit, inhibiting 70S initiation complex–> inhibits protein synthesis

Bacteriostatic
Time-dependent–> Linezolid
Concentration-dependent–>Tedizolid

Question 2

MOR

Answer 2

Alterations in the ribosomal binding site 23S subunit (rare)

Question 3

Spectrum of activity

Answer 3

Similar for both agents

Gram (+) aerobes:
- PRSP
- Enterococcus faecium AND faecalis (VRE)
- MRSA, MSSA, VISA, VRSA

Question 4

Pharmacology

Answer 4

PAE

Question 5

Absorption

Answer 5

linezolid is rapidly and completely absorbed after oral administration with an oral bioavailability of 100%

Question 6

Distribution

Answer 6

Readily distribute into well-perfused tissues

Linezolid serum concentrations are achieved in the CSF

Question 7

Elimination

Answer 7

Both agents are eliminated by both renal and non-renal routes

Linezolid is removed by hemodialysis

NO DOSE ADJUSTMENTS

Question 8

Clinical uses

Answer 8

VRE infections (bacteremia, UTI)

Nosocomial pneumonia due to MRSA–> Linezolid

Can be used first line in patients who are not on SSRI and platelets are > 15,000

Question 9

Drug interactions

Answer 9

MAO inhibitors

Risk of serotonin syndrome in patients receiving concomitant serotonergic agents (SSRIS)

Question 10

Adverse effects

Answer 10

GI–> N/V/D

CNS–> headache, peripheral neuropathy

Thrombocytopenia and anemia–> treatment > 2 weeks