Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Synercid IV (Rhone-Poulenc Rorer)
vials containing 500 mg for reconstitution
Approved indication: specified infections
Australian Medicines Handbook Section 5.1.13
Overuse of antibiotics has contributed to the development of resistant organisms. There is an urgent need for new treatments for the vancomycin-resistant enterococci which have recently emerged. The streptogram in antibiotics may have a role.
Quinupristin and dalfopristin are derived from the pristinamycins. The combination of the two drugs acts synergistically to inhibit bacterial protein synthesis. This makes the combination bactericidal. It is mainly effective against Gram-positive aerobic bacteria.
After infusion over an hour the combination is rapidly metabolised. These metabolites contribute to the antimicrobial actions. Most of the combination and its metabolites are excreted in the faeces.
Although many bacteria are susceptible to quinupristin and dalfopristin, the combination should be reserved for the treatment of vancomycin-resistant Enterococcusfaecium and methicillin-resistant Staphylococcus aureus (MRSA).As the combination often has to be used in an emergency where no other treatment is available, the efficacy of the combination is difficult to evaluate. In one case control study the mortality was lower in the control group, but fewer patients given the combination died as a result of vancomycin-resistant infection.1 In general, treatment of infections due to MRSA will have a higher success rate.
Approximately 11% of patients have to discontinue treatment because of reactions at the infusion site. They commonly experience pain, inflammation and oedema. To try to reduce these reactions the intravenous line should be flushed with 5% glucose. Flushing with heparin or saline is not recommended as the quinupristin/dalfopristin combination is incompatible with saline.
Systemic adverse reactions caused 6% of patients to stop treatment. These reactions include arthralgia, myalgia, nausea, vomiting and rashes. Liver function may also be affected.
The quinupristin/dalfopristin combination inhibits the enzyme cytochrome CYP 3A4. It can therefore inhibit the metabolism of drugs such as midazolam and nifedipine.
While this new product may help some patients with severe infections, it is important not to overlook the basic principles of management. For example, surgical debridement and the removal of infected devices such as catheters may be essential for successful treatment.2
- Linden PK, Pasculle AW, McDevitt D, Kramer DJ. Effect of quinupristin/dalfopristin on the outcome of vancomycin-resistant Enterococcusfaecium bacteraemia: comparison with a control cohort. J Antimicrob Chemother1997;39 Suppl A:145-51.
- Lai KK. Treatment of vancomycin-resistant Enterococcusfaecium infections. Arch Intern Med 1996;156:2579-84.