Streptogramins

Streptogramins are natural cyclic peptide antibiotics made of two components, group A (for example dalfopristin) and group B (for example quinupristin), that are bacteriostatic alone and bactericidal together. Quinupristin-dalfopristin is the parenteral combination; pristinamycin is an oral natural streptogramin used in some countries. Both are active against MRSA, Enterococcus faecium (including vancomycin-resistant strains) and penicillin-resistant pneumococci.

Mechanism. Both components bind the 50S ribosomal subunit at adjacent sites. Group A binding induces a conformational change that increases group B affinity about 100-fold and blocks both peptide elongation and release of the peptide chain.

Pharmacokinetics. Quinupristin-dalfopristin is given intravenously only, half-lives 0.9 and 0.7 hours, and is metabolised by non-enzymatic conjugation with biliary excretion. It strongly inhibits CYP3A4. Pristinamycin is absorbed orally.

Spectrum. MSSA and MRSA, streptococci, E. faecium (including VRE), Corynebacterium jeikeium, Legionella, Mycoplasma. Enterococcus faecalis is intrinsically resistant (lsa efflux). Resistance by erm methylation removes bactericidal synergy.

• Quinupristin-dalfopristin: reserve parenteral agent with a mixed record and limited modern use; withdrawn from many markets.
• Pristinamycin: oral agent used in several French-speaking countries and India for skin, respiratory and bone infection.
• Virginiamycin: animal use only.

Representative regimens.

• Quinupristin-dalfopristin 7.5 mg/kg IV every 8 hours (every 12 hours in skin infection), infused over 60 minutes into a central line diluted in 5 percent glucose (incompatible with saline).
• Pristinamycin 2 to 3 g orally daily in two or three divided doses with food, for community-acquired pneumonia, skin infection and bone and joint infection; duration depends on the site.

Selection. Reserve for VRE faecium or MRSA infection when linezolid, daptomycin or other options are unsuitable. Pristinamycin is used where marketed. Neither agent is usually available in East Africa.

Contraindications. Hypersensitivity; combination with CYP3A4 substrates that have a narrow margin (cisapride, pimozide, ergot alkaloids, simvastatin) is avoided.

Serious and common effects. Arthralgia and myalgia (up to 30 percent with quinupristin-dalfopristin, dose-limiting); infusion-site pain and phlebitis (central access advised); nausea, diarrhoea; hyperbilirubinaemia and raised transaminases; rarely thrombocytopenia and QT prolongation.

Interactions. Strong CYP3A4 inhibition raises levels of ciclosporin, tacrolimus, midazolam, nifedipine, methylprednisolone, some statins, and antiretroviral protease inhibitors; QT-prolonging drugs add risk.

Monitoring. Liver tests and bilirubin weekly; creatine kinase if severe myalgia; venous access review.

Special groups. Pregnancy and breastfeeding: avoided due to limited data. Renal impairment: no adjustment. Hepatic impairment: caution with moderate to severe impairment. Children: limited data for quinupristin-dalfopristin.