Quinupristin/dalfopristin explained

Quinupristin/dalfopristin, or quinupristin-dalfopristin, (pronunciation: kwi NYOO pris tin / dal FOE pris tin) (trade name Synercid) is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium.

Quinupristin and dalfopristin are both streptogramin antibiotics, derived from pristinamycin. Quinupristin is derived from pristinamycin IA; dalfopristin from pristinamycin IIA. They are combined in a weight-to-weight ratio of 30% quinupristin to 70% dalfopristin.

Administration

Intravenous, usually 7.5 mg/kg every 8 hours (infections/life threatening VRSA); every 12 hours (skin infections).No renal dosing adjustments, hepatic dosing adjustments are not defined, consider reducing dose.

Mechanism of action

Quinupristin and dalfopristin are protein synthesis inhibitors in a synergistic manner. While each of the two is only a bacteriostatic agent, the combination shows bactericidal activity.

• Dalfopristin binds to the 23S portion of the 50S ribosomal subunit, and changes the conformation of it, enhancing the binding of quinupristin^[1] by a factor of about 100. In addition, it inhibits peptidyl transfer.
• Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide, as well as causing incomplete chains to be released.

Pharmacokinetics

Clearance by the liver CYP450:3A4 inhibitor, half-life quinupristin 0.8 hours, dalfopristin 0.7 hours (with persistence of effects for 9–10 hours).

Side effects

^[2] Serious:

1. C.diff-associated diarrhea
2. superinfection
3. anaphylactoid reactions
4. angioedema

Common:

1. Joint aches (arthralgia) or muscle aches (myalgia)
2. Nausea, diarrhea (C. diff associated) or vomiting
3. Rash or itching
4. Headache
5. Hyperbilirubinemia
6. Anemia
7. Thrombophlebitis

Drug interactions

The drug inhibits P450 and enhances the effects of terfenadine, astemizole, indinavir, midazolam, calcium channel blockers, warfarin, cisapride and ciclosporin.

Further reading

• Allington DR, Rivey MP . Quinupristin/dalfopristin: a therapeutic review . Clinical Therapeutics . 23 . 1 . 24–44 . January 2001 . 11219478 . 10.1016/S0149-2918(01)80028-X .
• Lamb HM, Figgitt DP, Faulds D . Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections . Drugs . 58 . 6 . 1061–97 . December 1999 . 10651391 . 10.2165/00003495-199958060-00008 . 209144323 .
• Manzella JP . Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections . American Family Physician . 64 . 11 . 1863–6 . December 2001 . 11764864 . .
• Paradisi F, Corti G, Messeri D . Antistaphylococcal (MSSA, MRSA, MSSE, MRSE) antibiotics . The Medical Clinics of North America . 85 . 1 . 1–17 . January 2001 . 11190346 . 10.1016/s0025-7125(05)70302-3 . 2158/329747 . free .
• Web site: Synercid . https://web.archive.org/web/20070618100658/http://www.fda.gov/cder/consumerinfo/druginfo/SYNERCID.htm . dead . 2007-06-18 . U.S. Food and Drug Administration .

Notes and References

1. Book: Denyer SP, Hodges N, Gorman SP . Hugo and Russell's Pharmaceutical microbiology . 2004 . Blackwell Science . 978-0-632-06467-0 . 7th . 212 .
2. Epocrates v 19.5