Antibiotics 4.1 - Streptogramins and Oxazolidinones

Question 1

Streptogramins are a ___ derivatives of a natural mixture of ____ and _____.

(Isolated from?)

Answer 1

Semisynthetic derivatives of Pristinamycin I and II

Isolated from Streptomyces pristinaspiralis

Question 2

Synercid combo =

Answer 2

30% Quinupristin

70% Dalfopristin

Question 3

Quinupristin and Dalfopristin have side chains that…

Answer 3

Have amino side chains that allow salt formation

(Enhance water solubility)

Question 4

Each (Quin/Dalf) given alone is ______, but when given together are ________.

Answer 4

Each is bacteriostatic, but together are bactericidal

Question 5

Dalfopristin MOA

Answer 5

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)

Question 6

Quinupristin MOA

Answer 6

Binds in the ribosomal tunnel and causes blockage in the tunnel.

Question 7

Binding of Quin/Dalf results in…

Answer 7

a very stable ternary dalfo-quinu-ribosome complex

(1:1:1 stoichiometry)

Question 8

Dalfo and Quinu bind to the _____ within the ribosome

Answer 8

23S rRNA

Question 9

Mutation in _____, which gates the exit tunnel, confers resistance to ______

Answer 9

A2062

Streptogramin

Question 10

Synercid uses

Answer 10

1. VREf (Vanc resistant E. faecium)
2. MRSA (cutaneous)
3. VREf UTIs

Question 11

Most common resistance to quinupristin

Answer 11

adenine methylation of A2058 in 23S rRNA

(as in erythro+clinda)

Question 12

In addition to methylation of A2058, restistance to streptogramins can also be due to…

Answer 12

efflux + enzymatic inactivation

Question 13

Cure rate of VREf by Streptogramins

Answer 13

70%

Question 14

Streptogramin reserved for serious life threatening infctns caused by _____

Answer 14

Gram positives

Question 15

What is virginiamycin

Answer 15

Streptogramin that is used in animal feeds

increases the indicience of AB resistance

Question 16

Average Streptogramin T_1/2

Answer 16

1.5 hrs in serum

(linear relationship between dose and AUC)

Question 17

BBB penetration in Streptogramin

Answer 17

N/A

Question 18

Macrophage Streptogramin PK’s?

Answer 18

Concentrate the drug up to 50X the ECF concentration

Question 19

Clearance of Streptogramin is _______

Answer 19

75% biliary

(remainder = renal)

Question 20

DDI for Streptogramin

Answer 20

Inhibit CYP3A4

(warfarin, diazepam, astemizole, terfenadine, cisapride, NNRTI’s, cyclosporine)

Question 21

Oxazolidinones compounds

Answer 21

Linezolid (available)

Eperezolid (experimental)

Question 22

What separates linezolid in terms of MOA?

Answer 22

Interacts with 50S subunit (with micromolar affinity)

–> Prevents formation of the 70S initiation complex

*most AB’s inhibit protein synthesis at the elongation stage

Question 23

Linezolid interacts specifically with _____

Answer 23

23S rRNA

Question 24

Linezolid is used to treat: (3)

Answer 24

1. VREf
2. Nosocomial MRSA’s
3. Cutaneous MRSA’s

Question 25

Linezolid ROA’s

Answer 25

Oral (high BA) and I.V.

Question 26

Important consideration when choosing Linezolid as a treatment

Answer 26

Should only be used to treat of prevent infections that are proven or strongly suspected to be caused by multiple drug-resistant Gram+ bacteria

Question 27

Linezolid resistance organisms

Answer 27

MRSA, E.coli, others

Question 28

Linezolid mechanism of resistance

Answer 28

Target site modification = reduced affinity of linezolid to the 50S subunit

G->U mutation in Peptidyltransferase at position 2576

Question 29

Most common Linezolid sides

Answer 29

N/V/D

also headache, tongue discoloration and oral Candida

Question 30

Long term use of Linezolid sides (2)

Answer 30

Myelosuppression

Neuropathy

Question 31

BA and Half life of Linezolid oral

Answer 31

100% BA

4-6 hrs T_1/2

Question 32

Linezolid effect on P450

Answer 32

Neither an inducer nor an inhibitor

Question 33

Linezolid effect on MAO

Answer 33

Reversible nonselective inhibitor of MAO

DDI with serotonergic or adrenergic agents

(–> avoid tyramine)