General Information

Synercid (quinupristin and dalfopristin powder for injection) is a streptogramin antibacterial agent.

Synercid is indicated in adults with complicated skin and skin structure infections caused by Staphylococcus aureus (methicillin susceptible) or Streptococcus pyogenes.

Synercid should be administered by intravenous infusion in 5% Dextrose in Water solution over a 60-minute period. An infusion pump or device may be used to control the rate of infusion. If necessary, central venous access (e.g., PICC) can be used to administer Synercid to decrease the incidence of venous irritation. The recommended dosage for the treatment of complicated skin and skin structure infections is 7.5 mg/kg q12h. The minimum recommended treatment duration for complicated skin and skin structure infections is seven days.

Mechanism of Action

The site of action of quinupristin and dalfopristin is the bacterial ribosome. Dalfopristin has been shown to inhibit the early phase of protein synthesis while quinupristin inhibits the late phase of protein synthesis. Synercid is bactericidal against isolates of methicillin-susceptible and methicillin-resistant staphylococci. The mode of action of Synercid differs from that of other classes of antibacterial agents such as ß-lactams, aminoglycosides, glycopeptides, quinolones, macrolides, lincosamides and tetracyclines. Therefore, there is no cross resistance between Synercid and these agents when tested by the minimum inhibitory concentration (MIC) method.

Side Effects

Adverse effects associated with the use of Synercid may include the following:

• Inflammation, pain and edema at injection site
• Infusion site reaction
• Nausea

Clinical Trial Results

Two randomized, open-label, controlled clinical trials of Synercid (7.5 mg/kg q12h intravenously [iv]) in the treatment of complicated skin and skin structure infections were performed. The comparator drug was oxacillin (2g q6h iv) in the first study (JRV 304) and cefazolin (1g q8h iv) in the second study (JRV 305); however, in both studies vancomycin (1g q12h iv) could be substituted for the specified comparator if the causative pathogen was suspected or confirmed methicillin-resistant staphylococcus or if the patient was allergic to penicillins, cephalosporins or carbapenems. Study JRV 304 enrolled 450 patients (n = 229 Synercid; n= 221 Comparator) and Study JRV 305 enrolled 443 patients (n = 221 Synercid; n = 222 Comparator).

In the first study, 105 patients (45.9%) and 106 patients (48.0%) in the Synercid and Comparator arms, respectively, were found to be clinically evaluable. For the second study, these values were 113 (51.1%) and 120 (54.1%) patients in the Synercid and Comparator arms, respectively. Patients were found not to be clinically evaluable for reasons such as: wrong diagnosis, lower extremity infection in patients with diabetes or peripheral vascular disease since these infections were assumed to include aerobic gram-negative and anaerobic organisms, no specimen for culture obtained, insufficient therapy, no test of cure assessment, etc.

For the patients found to be clinically evaluable, in Study JRV 304 the success rate was 49.5% in the Synercid arm and 51.9% in the Comparator arm. In Study JRV 305, the success rates were 66.4% and 64.2% in the Synercid and Comparator arms, respectively.