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.
CONCLUSIONS:
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.