Quinupristin-Dalfopristin Mesylate is a 70:30 (w/w) complex of two semi-synthetic analogues of pristinamycin marketed as Synercid. Quinupristin-dalfopristin was developed in 1989 by the Rhône-Poulenc company in France. Dalfopristin is a semisynthetic analogue of Pristinamycin IIA (RP 54476), while quinupristin is a semi-synthetic analogue of Pristinamycin I (RP 57669).
To optimise stability, the compounds are presented as the mesylate salts with 10% sodium mesylate excess to provide a buffered aqueous solution. The complex is more hydrophobic than the naturally-occurring virginiamycin complex, with a readily ionisable group for generating a salt for improved solubility.
While both dalfopristin and quinupristin have bacteriostatic effects, they act synergistically to kill gram-positive bacteria, as well as some gram-negative and anaerobic bacteria. Dalfopristin binds to the 23s portion of the 50s ribosomal subnit and inhibits peptidyl transfer, as well as changing conformation to enhance binding of quinupristin. Quinupristin binds to a nearby site on the 50s ribosomal subunit and prevent elongation of the polypeptide as well as incomple polypeptide chains to be released prematurely.
Quinupristin-Dalfopristin Mesylate is soluble in ethanol, methanol, DMF and DMSO.
To optimise stability, the compounds are presented as the mesylate salts with 10% sodium mesylate excess to provide a buffered aqueous solution. The complex is more hydrophobic than the naturally-occurring virginiamycin complex, with a readily ionisable group for generating a salt for improved solubility.
While both dalfopristin and quinupristin have bacteriostatic effects, they act synergistically to kill gram-positive bacteria, as well as some gram-negative and anaerobic bacteria. Dalfopristin binds to the 23s portion of the 50s ribosomal subnit and inhibits peptidyl transfer, as well as changing conformation to enhance binding of quinupristin. Quinupristin binds to a nearby site on the 50s ribosomal subunit and prevent elongation of the polypeptide as well as incomple polypeptide chains to be released prematurely.
Quinupristin-Dalfopristin Mesylate is soluble in ethanol, methanol, DMF and DMSO.
| Mechanism of Action | While both dalfopristin and quinupristin have bacteriostatic effects, they act synergistically to kill gram-positive bacteria, as well as some gram-negative and anaerobic bacteria. Dalfopristin binds to the 23s portion of the 50s ribosomal subnit and inhibits peptidyl transfer, as well as changing conformation to enhance binding of quinupristin. Quinupristin binds to a nearby site on the 50s ribosomal subunit and prevent elongation of the polypeptide as well as incomple polypeptide chains to be released prematurely. |
| Spectrum | Quinupristin/dalfopristin is active against a range of gram-positive bacteria including meticillin- and multidrug-resistant strains of Staphylococcus aureus and S. epidermidis, vancomycin-resistant Enterococcus faecium (but not E. faecalis), and penicillin- and macrolide-resistant Streptococcus pneumoniae. It is also active against the anaerobe Clostridium perfringens, and Gram-negative bacteria Legionella pneumophila, Moraxella catarrhalis (Branhamella catarrhalis), Mycoplasma pneumoniae, and Neisseria meningitidis |
| Microbiology Applications | Quinupristin/dalfopristin received approval for use in adults for the treatment of infections caused by susceptible strains of vancomycin-resistant Enterococcus faecium(VREF) and for the treatment of complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible) or Streptococcus pyogenes |
| Eukaryotic Cell Culture Applications | In vitro drug interaction studies have shown that Synercid (Quinupristin/dalfopristin) significantly inhibits cytochrome P450 3A4. Synercid has been shown to be a major inhibitor (in vitro inhibits 70% cyclosporin A biotransformation at 10 mcg/mL of Synercid) of the activity of cytochrome P450 3A4 isoenzyme. The Pip/ptr promoter complex was dissociated by pristinamycin I but not by any of the other non-streptogramin antibiotics. These prokaryotic regulatory elements served as the basis for the development of systems allowing repression or induction of cloned genes in mammalian and plant cells in response to streptogramin antibiotics including pristinamycin, virginiamycin, and Synercid. |
| Cancer Applications | In cancer patients, quinupristin-dalfopristin treatment is associated with a relatively high frequency of myalgias/arthralgias; however, profound thrombocytopenia might limit the choice of linezolid in a subpopulation of cancer patients |
| Molecular Formula | C54H71N9O13S2 (for quinupristin mesylate); C35H54N4O12S2 (for dalfopristin mesylate) |
| Molecular Weight | 1118.3 (for quinupristin mesylate) ; 786.9 (for dalfopristin mesylate) |
| References | Quinupristin/dalfopristin (RP 59500): A new streptogramin antibiotic. Chant C. et al. Ann. Pharm. 1995, 29, 1022. Quinupristin/dalfopristin: spectrum of activity, pharmacokinetics, and initial chemical experience. Low D. Microb. Drug Resist. 1995, 1, 223. Quinupristin/dalfopristin: a therapeutic review. Allington D.R. & Rivey M.P. Clin. Ther. 2001, 23, 24. https://www.pfizermedicalinformation.com/en-us/synercid Folcher, M., Morris, R. P., Dale, G., Salah-Bey-Hocini, K., Viollier, P. H., & Thompson, C. J. (2001). A Transcriptional Regulator of a Pristinamycin Resistance Gene inStreptomyces coelicolor. Journal of Biological Chemistry, 276(2), 1479-1485. Delgado G., Jr., Neuhauser M. M., Bearden D. T., Danziger L. H. (2000). Quinupristin-dalfopristin: an overview. Pharmacotherapy 20, 1469–1485. 10.1592/phco.20.19.1469.34858 Manzella J. P. (2001). Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am. Fam. Phys. 64, 1863–1866. Gurk-Turner C. (2000). Quinupristin/dalfopristin: the first available macrolide-lincosamide-streptogramin antibiotic. Proceedings (Baylor University. Medical Center), 13(1), 83-6. Issam Raad, Ray Hachem, Hend Hanna, Claude Afif, Carmen Escalante, Hagop Kantarjian, Kenneth Rolston; Prospective, randomized study comparing quinupristin–dalfopristin with linezolid in the treatment of vancomycin-resistant Enterococcus faecium infections, Journal of Antimicrobial Chemotherapy, Volume 53, Issue 4, 1 April 2004, Pages 646–649, |
