Streptogramins are a class of natural cyclic peptide antibiotics that inhibit bacterial protein synthesis. They consist of two classes, A and B, that interfere with binding sites on the 50S ribosomal subunit. Commercially available quinupristin/dalfopristin is a combination of these two classes and has a bactericidal effect. It is considered a last resort for treating infections caused by vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Common side effects include phlebitis and pain during infusion, which can be managed through dilution of the solution and flushing the vein with saline after infusion. The drug should be used cautiously in patients with

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 .
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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
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• 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
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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.
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[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.
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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] .
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[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
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Kind regards