- Overview
- FDA-accelerated approval for:
- IV
treatment of bacteremia &
life-threatening infection due to
vancomycin (Vancocin)-resistant Enterococcus
faecium (VREF)
- Treatment
of complicated skin & skin
structure infections due to Staphylococcus
aureus and Streptococcus
pyrogenes
- Quinuprisin/dalfopristin (Synercid): properties
- two streptogramin
antibacterials (30:70 combination)
- Target: bacterial
ribosomes
- Effect: disruption of
protein synthesis
- Antibacterial
Characteristics:
- Active: against E. faecium
(not against Enterococcus
faecalis)
- Active (in vitro): against
methicillin (Staphcillin)-susceptible
and-resistant S. aureus and S.
epidermidis
- Active (in vitro): against
penicillin-susceptible &-resistant Streptococcus
pneumoniae
- Active (in vitro): against
- Neisseria
meningitidis, Moraxella
cattarrhalis, Legionella
pneumophila, Mycoplasma
pneumoniae, Clostridium
perfringens
- Pharmacokinetics
- IV administration
- hepatic metabolism
- biliary excretion
- Some clinical trial results:
- quinuprisin/dalfopristin (Synercid) --
- as effective as
vancomycin (Vancocin) in treating
catheter-related bacteremia due
to S. aureus
- effective in
treatingVREF in aortic graft
- effective in
treating a prosthetic valve
- effective in
treating pericarditis is
associated with continuous
peritoneal dialysis
- Adverse
Effects:
- Infusion site pain,
inflammation, edema, thrombophlebitis --
frequency: 75%
- Arthralgias & myalgias:
common, may be severe
- Drug-drug interactions
- quinuprisin/dalfopristin (Synercid) inhibitor of CYP3A4
(cytochrome P450 3A4) -- suggests
cautious use in patients taking
drugs metabolized by this enzyme
- Increased
serum nifedipine (Procardia, Adalat)
concentration
- Increased
midazolam (Versed) serum
concentration
- Increased
cyclosporine (Sandimmune,
Neoral) serum
concentration
- Co-administration
of
quinuprisin/dalfopristin
(Snercid) and drugs
metabolized by CYP3A4
which may prolong Q-T
intervals should be
avoided (example:
cisapride (Propulsid))
- Clinical Use--
conclusion
- Quinuprisin/dalfopristin (Synercid) --
modestly
effective for treatment of vancomycin
(Vancocin)-resistant Enterococcus faecium bacteremia-- this
effect may be life-saving
- High incidence of
side effects and adverse drug-drug
interactions suggest
quinuprisin/dalfopristin (Synercid)
should only rarely be used to treat any
other type of infection
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