Streptogramins are a ___ derivatives of a natural mixture of ____ and _____.
Semisynthetic derivatives of Pristinamycin I and II
Isolated from Streptomyces pristinaspiralis
Synercid combo =
Quinupristin and Dalfopristin have side chains that...
Have amino side chains that allow salt formation
(Enhance water solubility)
Each (Quin/Dalf) given alone is ______, but when given together are ________.
Each is bacteriostatic, but together are bactericidal
Directly interferes with the peptidyl transferase-catalyzed step.
(PT = Formation of bond between two amino acids, while breaking the bond between the fmet and its tRNA)
Binds in the ribosomal tunnel and causes blockage in the tunnel.
Binding of Quin/Dalf results in...
a very stable ternary dalfo-quinu-ribosome complex
Dalfo and Quinu bind to the _____ within the ribosome
Mutation in _____, which gates the exit tunnel, confers resistance to ______
VREf (Vanc resistant E. faecium)
- VREf UTIs
Most common resistance to quinupristin
adenine methylation of A2058 in 23S rRNA
(as in erythro+clinda)
In addition to methylation of A2058, restistance to streptogramins can also be due to...
efflux + enzymatic inactivation
Cure rate of VREf by Streptogramins
Streptogramin reserved for serious life threatening infctns caused by _____
What is virginiamycin
Streptogramin that is used in animal feeds
increases the indicience of AB resistance
Average Streptogramin T1/2
1.5 hrs in serum
(linear relationship between dose and AUC)
BBB penetration in Streptogramin
Macrophage Streptogramin PK's?
Concentrate the drug up to 50X the ECF concentration
Clearance of Streptogramin is _______
(remainder = renal)
DDI for Streptogramin
(warfarin, diazepam, astemizole, terfenadine, cisapride, NNRTI's, cyclosporine)
What separates linezolid in terms of MOA?
Interacts with 50S subunit (with micromolar affinity)
--> Prevents formation of the 70S initiation complex
*most AB's inhibit protein synthesis at the elongation stage
Linezolid interacts specifically with _____
Linezolid is used to treat: (3)
- Nosocomial MRSA's
- Cutaneous MRSA's
Oral (high BA) and I.V.
Important consideration when choosing Linezolid as a treatment
Should only be used to treat of prevent infections that are proven or strongly suspected to be caused by multiple drug-resistant Gram+ bacteria
Linezolid resistance organisms
MRSA, E.coli, others
Linezolid mechanism of resistance
Target site modification = reduced affinity of linezolid to the 50S subunit
G->U mutation in Peptidyltransferase at position 2576
Most common Linezolid sides
also headache, tongue discoloration and oral Candida
Long term use of Linezolid sides (2)
BA and Half life of Linezolid oral
4-6 hrs T1/2
Linezolid effect on P450
Neither an inducer nor an inhibitor
Linezolid effect on MAO
Reversible nonselective inhibitor of MAO
DDI with serotonergic or adrenergic agents
(--> avoid tyramine)