Oxazolidinones Flashcards
MOA
Bacterostatic
Oxazolidinones bind to the 50S ribosomal subunit near the surface interface of the 30S subunit, producing inhibition of the 70S initiation complex for protein synthesis
Inhibit protein synthesis
Intro
Developed in response to need for antibiotics with activity against resistant gram positivies (VRE, MRSA, VISA)
Mechanism of resistance
- Alteration in fibosomal binding site (chromosomal mutations in genes encoding 23S or ribosomal proteins) - rare
- cross resistance with other protein synthesis inhibitors is unlikely
Spectrum of activity
Gram positive:
-Streptococcus pneumoniae (including PRSP)
-Enterococcus faecium AND faecalis (including VRE)
- Staphylococcus aureus and CNS (MSSA, MRSA, VISA, VRSA)
No gram negative
Drugs in class
Linezolid and Tedizolid
Pharmacology
T>MIC for linezolid
AUC/MIC tedizolid
both available oral and IV
PAE exists for Gram-positive organisms: 3 to 4 hours
Absorption
Oral absorption of linezolid is 100%
Oral absorption of Tedizolid is 91%
Distribution
Readily distributed into well perfused tissues
Linezolid CSF penetration
Elimination
Renally and nonrenally
Linezolid is removed by hemodialysis
no dose adjustment in renal insufficiency
Clinical use
Not commonly used
Reserved for serious/complicated infections caused by resistant gram positive bacteria
VRE bacteremia or UTI -linezolid and tedizolid
Nosocomial pneumonia due to MRSA -linezolid
Can use first line for VRE if patient is not on SSRI or patients platelets are greater than 15,000
Drug interactions
Reversible inhibitors of monoamine oxidase
potential interaction with adrenergic and serotonergic agents
Serotonin syndrome with SSRIs - use with caution when using together
Adverse effects
- GI -N/V/D
- CNS- Headaches, peripheral and optic neuropathy
- Thrombocytopenia or anemia - common in those on prolonged therapy >2 weeks once therapy is D/C it will return to normal
