Streptogramin Antibiotics

Question 1

The streptogramins are ..

Answer 1

semisynthetic derivatives of a natural mixture of pristinamycin I and pristinamycin II isolated from Streptomyces pristinaspiralis

Question 2

How are streptograms administered

Answer 2

parenterally

there are other pristinamycin combinations under development that have useful oral activity

Question 3

What is the difference between streptomycins by themselves vs used in combination?

Answer 3

Each of these compounds is bacteriostatic alone, but in combination they provide a bactericidal mixture

Question 4

What is the mechanism of action of dalfopristin?

Answer 4

Directly interferes with the peptidyl transferase-catalyzed step in protein synthesis

(peptidyl transferase (ribosomal RNA) catalyzes the formation of a peptide bond between the two amino acids while breaking the bond between fmet and its tRNA)

Question 5

What is the mechanism of quinupristin?

Answer 5

Binds in the ribosomal tunnel and causes blockage of the tunnel

Question 6

What is synercid?

Answer 6

Mixture containing 30% quinupristin and 70% dalfopristin (weight ratio)

Question 7

Therapeutic uses of synercid

Answer 7

1. Vancomycin-resistant Enteroccus faecium bacteremia (it is not effective against Enterococcus faecalis infections)
2. Skin infections caused by MRSA
3. Vancomycin-resistant Enteroccus faecium urinary tract infections

Question 8

Resistance to Streptogramin antibiotics

Answer 8

1. Adenine methylation of A2058 in the 23S rRNA (as in the case of erythromycin and clindamycin). This renders synercid a bacteriostatic agent at the normal dose.
2. Efflux and enzymatic inactivation (metabolism) by resistant bacteria
3. The continued use of streptogramins (virginiamycin) in animal feeds will continue to result in more resistant bacterial strains

Question 9

Side effects of streptogramins

Answer 9

1. There is no known significant toxicity presented by synercid
2. Mild side effects: inflammation and pain at the site of injection, nausea, diarrhea, muscle weakness and rash

Question 10

Pharmacokinetics

Answer 10

Complicated because of the different elimination rates for each component and their metabolites

1. The average T1/2 is 1.5 hours in serum
2. Most tissues of importance achieve up to 85% of the serum concentrations of Synercid®
   - The blood/brain or placental barriers are not penetrated
   - Macrophages concentrate the drug up to 50X the extracellular fluid concentration
3. Clearance is 75% through biliary excretion (fecal matter) and the remainder appears in the urine

Question 11

Streptogramins drug interactions

Answer 11

Inhibit cytochrome CYP 3A4

CYP3A4 mebolizes

• -warfarin
• -diazepam
• -astemizole
• -terfenadine
• -cisapride
• -non-nucleoside reverse transcriptase inhibitors
• -cyclosporine