Nafcillin

Nafcillin is an intravenous penicillinase-resistant penicillin used mainly in the United States and similar services for serious methicillin-susceptible Staphylococcus aureus (MSSA) infection. It is cleared mainly by the liver, so kidney function matters little.

Classification. Beta-lactam, anti-staphylococcal penicillin.

Mechanism. Binds penicillin-binding proteins; resistant to staphylococcal beta-lactamase.

Spectrum. MSSA, beta-haemolytic streptococci, pneumococci. Inactive against MRSA, enterococci and Gram-negative bacilli.

Pharmacokinetics. Not reliably absorbed orally. Half-life about 30 to 60 minutes. Protein binding about 90%. Eliminated mainly by biliary excretion and hepatic metabolism. It is a recognised inducer of CYP3A4, CYP2C9 and P-glycoprotein, so it lowers levels of many co-prescribed drugs. Availability in East Africa is limited.

No loading dose. Maximum 12 g daily.

MSSA bacteraemia and endocarditis. 2 g IV every 4 hours for at least 14 days in uncomplicated bacteraemia and 4 to 6 weeks in native valve endocarditis. Prosthetic valve endocarditis: 2 g every 4 hours for 6 weeks or longer, with rifampicin and gentamicin.

Bone and joint infection, pneumonia, severe skin infection. 1 to 2 g IV every 4 to 6 hours; osteomyelitis for 6 weeks.

Central nervous system infection. 2 g IV every 4 hours.

Children. 100 to 200 mg/kg/day divided every 4 to 6 hours, maximum 12 g daily. Neonates: 25 to 50 mg/kg every 8 to 12 hours, depending on gestation.

Alternatives. Cefazolin (fewer interactions and easier dosing) or flucloxacillin or oxacillin; vancomycin in penicillin allergy or MRSA.

Contraindications. Penicillin hypersensitivity.

Adverse effects. - Phlebitis and tissue necrosis if extravasated; a central line is advised for courses over a few days. - Hypokalaemia and sodium load. - Interstitial nephritis, neutropenia (courses over 2 weeks), hepatitis, anaphylaxis, Clostridioides difficile infection.

Interactions. - Warfarin: marked fall in INR. - Ciclosporin, tacrolimus, voriconazole, and other CYP3A4 substrates: levels fall. - Oral contraceptives: possible reduction. - Methotrexate: higher levels. - Probenecid raises nafcillin levels.

Common prescribing errors. Missing the induction interactions, using peripheral lines for long courses, and omitting potassium monitoring.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: monitor potassium and liver tests. - Kidney impairment: no usual adjustment. - Liver impairment: caution; reduce dose in combined severe hepatic and renal failure. - Neonates: dose by gestation and age.

Preparation. Dilute 1 to 2 g in 50 to 100 mL of 0.9% sodium chloride or 5% glucose and infuse over 30 to 60 minutes. Continuous infusion of 12 g over 24 hours is used in some services through a central line. Contains about 2.9 mmol sodium a gram.

Baseline and monitoring. - Baseline: allergy history, creatinine, electrolytes, liver tests, INR if on warfarin. - During treatment: creatinine, potassium and liver tests twice weekly; full blood count weekly; INR twice weekly in warfarin users. - No therapeutic drug monitoring.

Stop rules. Stop for jaundice, severe rash, neutropenia, or anaphylaxis. Switch to cefazolin when interstitial nephritis or hypokalaemia becomes problematic.

Referral and escalation. Infectious diseases for every Staphylococcus aureus bacteraemia, endocarditis and implant-associated infection.