Quinupristin Dalfopristin

Quinupristin dalfopristin is a streptogramin combination (30:70) given by IV infusion for vancomycin-resistant Enterococcus faecium infection and complicated skin infection. It is a reserve agent with limited availability and a high rate of musculoskeletal and infusion-site adverse effects.

Classification. Streptogramin.

Mechanism. The two components bind the 50S ribosomal subunit at different sites and act synergistically, blocking protein synthesis; bactericidal against many Gram-positive cocci, bacteriostatic against others.

Spectrum. Vancomycin-resistant Enterococcus faecium, MRSA, MSSA, streptococci including penicillin-resistant pneumococci. Not active against Enterococcus faecalis, Enterobacterales or Pseudomonas.

Pharmacokinetics. IV only. Half-lives about 1 hour (quinupristin) and 1 hour (dalfopristin). Active metabolites. Mostly biliary and faecal excretion. Strong inhibitor of CYP3A4.

Reserve agent; limited availability. Dose by weight.

Adults. - Vancomycin-resistant Enterococcus faecium infection: 7.5 mg/kg IV every 8 hours (central venous access preferred). - Complicated skin and soft tissue infection: 7.5 mg/kg IV every 12 hours for at least 7 days. - Serious infection (specialist): combination with another active drug.

Children. Not established; limited experience at 7.5 mg/kg every 8 to 12 hours.

Alternatives. Linezolid, daptomycin, tedizolid, tigecycline, vancomycin.

Contraindications. Hypersensitivity to streptogramins.

Adverse effects. Infusion-site pain, inflammation and thrombophlebitis (frequent), arthralgia and myalgia (often severe, may need dose reduction), nausea, vomiting, diarrhoea, hyperbilirubinaemia, rash, headache. Serious: hepatotoxicity, Clostridioides difficile infection, anaphylaxis.

Interactions. CYP3A4 substrates (ciclosporin, tacrolimus, midazolam, nifedipine, simvastatin, many HIV protease inhibitors) have raised levels; QT-prolonging drugs (use with caution); drugs metabolised by CYP3A4 with narrow safety margin (avoid).

Common prescribing errors. Dilution in saline (precipitates: use 5% glucose only), peripheral infusion without flushing with glucose, and missing interaction review.

Special groups. - Pregnancy: avoid unless essential. Breastfeeding: avoid. - Older adults: usual dose; monitor for myalgia. - Kidney impairment: no adjustment; dialysis no adjustment. - Liver impairment: Child-Pugh A or B reduce the dose to 5 mg/kg every 8 hours or longer intervals if levels rise; avoid in Child-Pugh C. - Region: not generally available in East Africa.

Preparation. Reconstitute each 500 mg vial with 5 mL of sterile water or 5% glucose, then add to 250 mL of 5% glucose (no more than 500 mL in peripheral lines) and infuse over 60 minutes. Never dilute in saline. Flush lines with 5% glucose before and after.

Baseline and monitoring. - Baseline: liver tests, bilirubin, creatinine, medication review. - During treatment: liver tests weekly; creatine kinase if severe myalgia; infusion site inspection each dose.

Stop rules. Stop for severe arthralgia or myalgia not controlled by dose reduction, hepatotoxicity, anaphylaxis or severe infusion-site reaction.

Referral and escalation. Infectious diseases consultation before use.