The pharmacology, pharmacokinetics, activity, and potential clinical role of
quinupristin-dalfopristin (
RP 59500) are described.
Quinupristin-dalfopristin is the first
injectable formulation of the
streptogramin antibiotics.
Streptogramin drug products are each composed of two chemically distinct compounds, which when administered together act synergistically by inhibiting
bacterial protein synthesis.
Quinupristin-dalfopristin has shown activity in vitro against many strains of streptococci and staphylococci, including
methicillin- and
erythromycin-resistant strains of staphylococci. The combination is more active against Enterococcus faecium than Enterococcus faecalis. It has also shown activity in vitro against certain gram-negative organisms and anaerobes. The mean maximum blood concentration at the end of a one-hour infusion ranged from 0.95 mg/L for a 1.4-mg/kg dose to 24.2 mg/L for a 29.4-mg/kg dose; there was a linear correlation between dose and mean area under the concentration-time curve. Mean half-life ranged from 1.27 to 1.53 hours. The
drug is under investigation in the United States in Phase III trials. Of 60 evaluable patients with documented
bacteremia involving E. faecium resistant to
vancomycin, 40 (67%) had a favorable clinical response. Of 11 patients with
bacteremia caused by methicillin-resistant Staphylococcus aureus, 78% had a favorable response. The efficacy of
quinupristin-dalfopristin in treating resistant
infections has also been suggested by smaller studies and case reports. The
drug may be useful in the prophylaxis of
endocarditis. Adverse reactions are generally mild and transient.
Quinupristin-dalfopristin may be useful in treating serious gram-positive
infections, but more clinical study is needed.