Streptogramins

Agent: quinupristin/dalfopristin

The increase in resistance to antibiotics among staphylococci and enterococci led to pharmaceutical companies increasing the development of drugs to combat these resistant infections. One of the first of the newer drugs to treat VRE and MRSA infections was quinupristin/dalfopristin. These drugs are two different streptogramins given in a combined formulation. Though each separate streptogramin is bacteriostatic, when given together they act synergistically to give bactericidal activity against some Gram-positive cocci; hence the brand name of this drug: Synercid®. Quinupristin/dalfopristin initially enjoyed frequent use, particularly to treat VRE infections, but its use has lessened as other agents have come on the market. Other streptogramins have been developed and are used in animals as growth promoters, a questionable but common practice in modern agriculture.

Spectrum

Good: MSSA, MRSA, streptococci,  Enterococcus   faecium (including vancomycin-resistant strains)

Poor : Enterococcus faecalis, anything Gram-negative .

Adverse Effects

Quinupristin/dalfopristin can cause phlebitis and ideally should be administered via a central line. It is also associated with a high incidence of myalgias and arthralgias that can limit tolerance to therapy.  Quinupristin/dalfopristin also inhibits cytochrome P450 3A4, so clinicians need to be aware of potential drug interactions.

Important Facts

• Quinupristin/dalfopristin must be mixed and administered with 5% dextrose in water (D5W)  solutions only. When mixed with normal saline,  the drug becomes insoluble and can crystallize,  even when a patient’s IV line is flushed with saline. Be sure that your patient’s nurses know to flush the line with D5W or another saline-free diluent. The drug is not available orally.

• The arthralgias and myalgias associated with quinupristin/dalfopristin are significant and should not be underestimated. It may be possible to decrease their severity by decreasing the dose, but this could compromise efficacy.

What It’s Good For

Infections caused by E. faecium or MRSA in patients not responding to or intolerant of other medications.

Don’t Forget!

Quinupristin/dalfopristin is not active against Enterococcus faecalis. Between the two most common clinical species of Enterococcus (E. faecalis and E.  faecium), E. faecalis is more common in most hospitals, but it is less likely to be resistant to vancomycin. For this reason, quinupristin/dalfopristin is better employed as a definitive therapy than an empiric one for enterococci unless you strongly suspect E. faecium infection.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.