Streptogramin and Oxazolidinone Flashcards
What two antibiotics are found in synercid?
quinuprisitin and dalfopristin
What part of the structure of quinupristin and dalfopristin allow salt formation and enhance water solubility?
- amino side chains
Is quinupristin bactericidal or bacteriostatic
bacteriostatic
Is dalfopristin bactericidal or bacteriostatic
bacteriostatic
are quinupristin and dalfopristin used together bactericidal or bacteriostatic
bactericidal!
How are streptogramins administered?
parenterally
What is the mechanism of action of dalfopristin?
- dalfopristin directly interferes with the peptidyl transferase-catalyzed step of peptide synthesis
- inhibits amino acids from linking with each other (A –> P site)
What is the mechanism of action of quinupristin
binds the ribosomal tunnel and blocks causes blockage of the tunnel
What are the therapeutic uses of synercid?
- VRE (enteroccus faecium)
- skin infections caused by MRSA
- vancomycin resistant enteroccus faecium urinary track infections
What part of the ribosome does synercid bind to
23S rNA
What is the quinupristin resistance mechanisms?
- adenine methylation of A2058 in the 23S rNA
- efflux and enzymatic inactivation
- this makes synercid bacteriostatic
- does not affect dalfopristin
How to overcome quinupristin resistance
extension of the dosing of synercid to TID allows for more sustained tissue drug levels
What are the side effects of synercid
- non known signficant toxicity presented by synercid
- inflammation and pain at site of injection
- nausea
- diarrhea
- muscle weakness
- rash
What is the PK of synercid
- complicated because of different elimination rates for each drug
- gram + infections achieve up to 85% of the serum concentrations
- blood/brain or placental barriers are not penetrated
- clearance is 75% biliary excretion
What are the potential drug interactions associated with synercid
- inhibit cyp 3A4
What is the mechanism of action of the oxazolidinones
inhibit bacterial protein synthesis at the peptide chain elongation stage by potent interaction with the 50s ribosomal subunit
What is the main therapeutic use of linezolid
- vancomycin resistant enterococcus faecium
- nosocomial pneumonia caused by MRSA
- skin infections caused by MRSA
Why should linezolid used only to treat or prevent infections that are proven or strongly suspected to be caused by multiple drug resistance gram positive bacteria
to reduced the development of drug resistant bacteria and maintain the effectiveness of linezolid (the emergence of linezolid resistance has been reported)
What is the resistance mechanism of linezolid
- target site modification with G to U substitution in the peptidyl transferase center of the 23S rRNA at position 2576
- reduces affinity of linezolid to the 50s subunit
- mutations that lie in proximity of the P sigte which confirms the MOA of oxazolidinones
What are the main side effects of linezolid?
- GIeffects
- headache
- tongue discoloration
- thrush
- thrombocytopenia
- anemia
- GI bleeding
- fully reversible myelosuppression
- linezolid induced neuropathy
What is the main metabolic pathway of linezolid
morpholine ring oxidation
What is the PK of linezolid
- 100% bioavailable after oral adminiistration
- has half life of 4-6 hours
- orally or iv admin
What are the drug interactions associated with linezolid
- potent, reversible, nonselective inhibitor of MOAi
- potential interactions with adrenergic and serotenergic
- reversible potentiation of pressor response to pseudoephedrine
- should be used in caution in patients who are sensitive to increases in BP due to preexisting conditions
- tyramine
Compare the potency of tedizolid and linezolid
more potent than linezolid vs mrsa
compare the MOA of tedizolid and linezolid
same mechanism of action (tedizolid phosphate is tedizolid prodrug)
