1. Orientation
• All antibiotics inhibit the bacteria through three main
targets:
 Cell wall.
 Bacterial DNA.
 Bacterial ribosome.
1

2. 2

3. Introduction
• What are streptogramins?
• Classification.
• Mechanism of action.
• When to use them?
• What problems patient may face ?
• Precautions should be taken in mind .
3

4. What are streptogramins?
• The streptogramin antibiotics :
Natural cyclic peptide antibiotics produced by
certain sub-species of Streptomyces.
Structurally related to macrolides and
lincosamides.
Strepogramins abstract Date of access 27/3/2012
http://dx.doi.org/10.2174/1389450023347678 4

5. What are streptogramins?
(cont.)
• The streptogramin antibiotics :
 Discovered over 40 years ago.
 The agent received accelerated
approval by the FDA in late 1999[1]!!
5
[1]Koda-Kimble, Mary Anne; Young, Lloyd Yee; Alldredge, Brian K.; Corelli, Robin L.; Guglielmo, B. Joseph;
Kradjan, Wayne A.; Williams, Bradley R.; Applied Therapeutics: The Clinical Use Of Drugs, Lippincott
Williams & Wilkins.; Philadelphia; 9th Edition,2009 ; P.59p20.

6. Streptogramins
classes
6
Cyclic peptides include two
structurally unrelated components
Group A
Dalfopristin
Inhibit the early phase
of protein synthesis
Group B
Quinupristin
Inhibits the late phase
of protein synthesis
Antibiotic classes date of access: 3/30/2012
http://www.bmb.leeds.ac.uk/mbiology/ug/ugteach/icu8/an
tibiotics/protein.html

7. Mechanism of action
7
• The individual components are bacteriostatic.
• Their combination synergistically is bactericidal
combination.
• Quinupristin/dalfopristin are available in combination of
3:7 ratio respectively[1] .
• Combination is concentration dependent mechanism
with a long post-antibiotic effect.
[1]Sean C Sweetman; Martindale, The complete drug reference; Pharmaceutical Press;
London , ,Chicago; Thirty-sixth edition; 2009; vol. 1; page 322

8. Mechanism of action
(cont.)
Changes its conformation.
Inhibits the early phase of protein synthesis.
Dalfopristin
Binds to the 23S portion of the 50S ribosomal subunit.
8
Hugo and Russell's pharmaceutical microbiology Authors: William Barry Hugo, Stephen P. Denyer, Norman
A. Hodges, Sean P. Gorman Edition: 7, illustrated Publisher: Wiley-Blackwell, 2004 ISBN: 0632064676,
9780632064670 Length: 481 pages

9. Mechanism of action
(cont.)
Inhibits the late phase of protein synthesis
Prevents elongation of the polypeptide
Causing incomplete chains to be released
Quinupristin
Binds to a nearby site on the 50S ribosomal subunit
9
Hugo and Russell's pharmaceutical microbiology Authors: William Barry Hugo, Stephen P. Denyer, Norman A.
Hodges, Sean P. Gorman Edition: 7, illustrated Publisher: Wiley-Blackwell, 2004 ISBN: 0632064676,
9780632064670 Length: 481 pages

10. In market !!
• Quinupristin/Dalfopristin
combination
is available as sterile lyophilized
formulation for intravenous
administration under trade name of
Synercid®.
239$ per vial
10

11. Therapeutic indications
• Synercid® is approved in the U.S. for treatment of:
 Vancomycin-resistant Enterococcus faecium(but not E.
faecalis) (VRE) induced bacteremia and complicated skin and
skin-structure infection.
 Infections caused by vancomycin resistant Staph. Aureus
(VRSA)
11
Laurence L. Brunton, PhD; Keith L. Parker, MD, PhD; Goodman & Gilman’s Manual of
Pharmacology and Therapeutics; McGraw-Hill Companies, Inc; 11th edition; 2008; SECTION
46; page 779.

12. Therapeutic indications
(cont.)
• In Europe, it is also approved for treatment of:
 Nosocomial pneumonia and infections
caused by methicillin-resistant strains
of S. aureus.
• Used for patients with vancomycin-resistant enterococcal
endocarditis[1] .
12
[1] Koda-Kimble, Mary Anne; Young, Lloyd Yee; Alldredge, Brian K.; Corelli, Robin L.; Guglielmo, B.
Joseph; Kradjan, Wayne A.; Williams, Bradley R.; Applied Therapeutics: The Clinical Use Of Drugs,
Lippincott Williams & Wilkins.; Philadelphia; 9th Edition ,2009; P.59p20 .

13. Side effects
 Nausea and vomiting
 Skin rash, pruritus
 Hyperbilirubinemia and raised liver enzyme
values may occur.
 Arthralgias and myalgias in patients with
hepatic insufficiency
 Managed by reducing the dosing
frequency from q. 8hr to q.12 hr
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14. Side effects (cont.)
 Pain and phlebitis at the infusion site are most
common & minimized by[1]:
 Infusion through a central venous catheter.
 Dilution of preparation to 500-750ml solution
with D5W .
 Increase infusion duration
to 60 minutes.
14
[1]Sean C Sweetman; Martindale, The complete drug reference; Pharmaceutical Press;
London , ,Chicago; Thirty-sixth edition; 2009; vol. 1; page 322.

15. Side effects (cont.)
 Pain and phlebitis at the infusion site are most
common & minimized by[1]:
 The vein should be flushed with D5W after each
infusion.
 Note that saline is in
compatible with Synercid®.
15
[1]Sean C Sweetman; Martindale, The complete drug reference; Pharmaceutical Press;
London , ,Chicago; Thirty-sixth edition; 2009; vol. 1; page 322.

16. Precautions
• Use synercid® with caution in case of:
o Hepatic impairment (avoid if severe).
o Cardiac patients e.g.:
Congenital QT syndrome.
 Concomitant use of drugs prolong QT interval.
 Cardiac hypertrophy.
 Dilated cardiomyopathy.
16
John Martin; BNF 57; BMJ Group & RPS Publishing; London, UK ; 57th Edition;
2009; vol. 5.1.1.; page 292.

17. Precautions (cont.)
• Use synercid® with caution in case of:
o Hypokalaemia, hypomagnesaemia, brady-cardia.
o Synercid® is pregnancy category B by FDA[1] .
17
[1] pregnancy & reproductive studies date of access: 3/30/2012
http://www.drugs.com/pro/synercid.html

18. Conclusion
• Streptogramins are class of natural cyclic
peptide antibiotics produced by certain sub-
species of Streptomyces .
• They are 2 classes A & B.
• They inhibit bacterial protein
synthesis by interfering 50S
ribosomal binding sites.
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19. • Commercially available product is mixture of
both Quinupristin/dalfopristin.
• Combination for bactericidal effect.
• Considered as the last resort against VRSA,
VRE induced bacteremia ,endocarditis, ….etc.
Conclusion (cont.)
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20. • Most common side effect is the phlebitis and the pain
during infusion.
 Dilution of the solution and vein flushing by D5W are
most effective management.
• Use with caution in case of hepatic impairment, cardiac
arrhythmias.
• Synercid® is pregnancy category B drug.
Conclusion (cont.)
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21. Thank you
21
Kind regards