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Quinupristin-dalfopristin (RP 59500): an injectable streptogramin combination.

Author(s): Griswold MW, Lomaestro BM, Briceland LL

Affiliation(s): Department of Pharmacy Practice, Albany College of Pharmacy, NY 12208, USA.

Publication date & source: 1996-09-01, Am J Health Syst Pharm., 53(17):2045-53.

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.

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