STREPTOGRAMINS
Quinupristin-dalfopristin is
a combination of two streptogramins—quinupristin, a streptogramin B, and
dalfopristin, a streptogramin A—in a 30:70 ratio. The streptogramins share the
same ribosomal binding site as the macrolides and clindamycin and thus inhibit
protein synthesis in an identical manner. It is rapidly bactericidal for most
susceptible organisms except Enterococcus
faecium, which is killed slowly. Quinupristin-dalfopristin is active
against gram-positive cocci, including multidrug-resistant strains of
strep-tococci, penicillin-resistant strains of S pneumoniae, methicillin-susceptible and -resistant strains of
staphylococci, and E faecium (but not
Enterococcus faecalis). Resistance is
due to modification of the quinupristin binding site (MLS-B type resistance),
enzymatic inactivation of dalfopristin, or efflux.
Quinupristin-dalfopristin
is administered intravenously at a dosage of 7.5 mg/kg every 8–12 hours. Peak
serum concentrations following an infusion of 7.5 mg/kg over 60 minutes are 3
mcg/mL for quinupristin and 7 mcg/mL for dalfopristin. Quinupristin and
dalfopristin are rapidly metabolized, with half-lives of 0.85 and 0.7 hours,
respectively. Elimination is principally by the fecal route. Dose adjustment is
not necessary for renal failure, perito-neal dialysis, or hemodialysis.
Patients with hepatic insufficiency may not tolerate the drug at usual doses,
however, because of increased area under the concentration curve of both parent
drugs and metabolites. This may necessitate a dose reduction to 7.5 mg/ kg
every 12 hours or 5 mg/kg every 8 hours. Quinupristin and dalfopristin
significantly inhibit CYP3A4, which metabolizes warfarin, diazepam, astemizole,
terfenadine, cisapride, nonnucleo-side reverse transcriptase inhibitors, and
cyclosporine, among others. Dosage reduction of cyclosporine may be necessary.
Quinupristin-dalfopristin
is approved for treatment of infections caused by staphylococci or by
vancomycin-resistant strains of E faecium,
but not E faecalis, which is
intrinsically resistant, prob-ably because of an efflux-type resistance
mechanism. The principal toxicities are infusion-related events, such as pain
at the infusion site, and an arthralgia-myalgia syndrome.
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