Quinupristin/dalfopristin : A review of its use in the management of serious gram-positive infections

• Published in: Drugs (New York, N.Y.) Vol. 58; no. 6; pp. 1061 - 1097
• Main Authors: LAMB, H. M, FIGGITT, D. P, FAULDS, D
• Format: Journal Article
• Language: English
• Published: Auckland Adis International 01.12.1999
• Subjects: Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Drug Resistance, Microbial; Gram-Positive Bacteria - drug effects; Gram-Positive Bacterial Infections - drug therapy; Gram-Positive Bacterial Infections - microbiology; Humans; Medical sciences; Pharmacology. Drug treatments; Virginiamycin - adverse effects; Virginiamycin - pharmacokinetics; Virginiamycin - pharmacology; Virginiamycin - therapeutic use; Human; Toxicity; Treatment efficiency; Quinupristin; Review; In vitro; Dalfopristin; Infection; In vivo; Antibiotic; Chemotherapy; Treatment; Gram positive bacteria; Streptogramins; Antibacterial agent; Pharmacokinetics
• ISSN: 0012-6667; 1179-1950
• DOI: 10.2165/00003495-199958060-00008

Quinupristin/dalfopristin is the first parenteral streptogramin antibacterial agent, and is a 30:70 (w/w) ratio of 2 semisynthetic pristinamycin derivatives. The combination has inhibitory activity against a broad range of gram-positive bacteria including methicillin-resistant staphylococci, vancomycin-resistant Enterococcus faecium (VREF), drug-resistant Streptococcus pneumoniae, other streptococci, Clostridium perfringens and Peptostreptococcus spp. The combination also has good activity against selected gram-negative respiratory tract pathogens including Moraxella catarrhalis, Legioniella pneumophila and Mycoplasma pneumoniae. Quinupristin/dalfopristin has poor activity against E. faecalis. The combination is bactericidal against staphylococci and streptococci, although constitutive erythromycin resistance can affect its activity. As for many other agents, quinupristin/dalfopristin is generally bacteriostatic against E. faecium. In patients with methicillin-resistant S. aureus (MRSA) or VREF infections participating in prospective emergency-use trials, quinupristin/dalfopristin 7.5 mg/kg every 8 or 12 hours achieved clinical or bacteriological success in > or =64% of patients. Emergence of resistance to quinupristin/dalfopristin was uncommon (4% of patients) in those with VREF infections. Quinupristin/dalfopristin 7.5 mg/kg 8- or 12-hourly also achieved similar clinical success rates to comparator agents in patients with presumed gram-positive complicated skin and skin structure infections or nosocomial pneumonia (administered in combination with aztreoman) in 3 large multicentre randomised trials. Systemic adverse events associated with quinupristin/dalfopristin include gastrointestinal events (nausea, vomiting and diarrhoea), rash and pruritus. Myalgias and arthralgias also occur at an overall incidence of 1.3%, although higher rates (2.5 to 31%) have been reported in patients with multiple comorbidities. Venous events are common if the drug is administered via a peripheral line; however, several management options (e.g. use of central venous access, increased infusion volume) may help to minimise their occurrence. Hyperbilirubinaemia has been documented in 3.1% of quinupristin/dalfopristin recipients versus 1.3% of recipients of comparator agents. Quinupristin/dalfopristin inhibits cytochrome P450 3A4 and therefore has the potential to increase the plasma concentrations of substrates of this enzyme. Quinupristin/dalfopristin, the first parenteral streptogramin, offers a unique spectrum of activity against multidrug-resistant gram-positive bacteria. In serious gram-positive infections for which there are other treatment options available, the spectrum of activity and efficacy of quinupristin/ dalfopristin should be weighed against its tolerability and drug interaction profile. However, in VREF or unresponsive MRSA infections, where few proven treatment options exist, quinupristin/dalfopristin should be considered as a treatment of choice for these seriously ill patients.