Quinupristin/dalfopristin

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 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
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.