MOA:
Inhibition of 50s ribosomal subunit
(Synercid) Is a mixture of two of two bacteriostatic drugs called streptogramins in a ratio of 30 to 70, respectively.
Activity against gram positive cocci. •
The comboination is:
Rapid bactericidal (synergism) as each component of this combination drug binds to a separate site on the 50S bacterial ribosome as dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis. The drug has a long PAE.
Due to significant adverse effects, the drug is normally reserved to be injected intravenously for the treatment of severe vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) infection in the absence of other therapeutic options this is due to its excellent penetration of macrophages and neutrophils. (i.e Alternative to vancomycin if resistance)
Both compounds undergo hepatic metabolism, with excretion mainly in the feces.
ADVERSE EFFECTS
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Venous irritation (phlebitis)commonly occurs when quinupristin/dalfopristin is administered through a peripheral rather than a central line. (should be administered via a central line).
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Hyperbilirubinemia occurs in about 25% of patients. Arthralgia and myalgia have been reported when higher doses are used which can limit tolerance to therapy (Side effects similar to quinolones)
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Quinupristin/ dalfopristin inhibits cytochrome P450 (CYP3A4) isoenzymeP450, and concomitant administration with drugs that are metabolized by this pathway may lead to toxicities.