Oxacillin

Oxacillin is an intravenous or intramuscular penicillinase-resistant penicillin with the same indications as nafcillin: serious methicillin-susceptible Staphylococcus aureus (MSSA) infection and streptococcal infection.

Classification. Beta-lactam, anti-staphylococcal penicillin.

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

Spectrum. MSSA and beta-haemolytic streptococci. Not active against MRSA, enterococci or Gram-negative bacilli.

Pharmacokinetics. Half-life about 30 to 60 minutes. Protein binding about 90%. Eliminated by kidney (about 50%) and liver. Less affected by renal failure than benzylpenicillin.

No loading dose. Maximum 12 g daily.

Moderate infection. 1 to 2 g IV every 4 to 6 hours.

MSSA bacteraemia and endocarditis, severe infection. 2 g IV every 4 hours; bacteraemia at least 14 days from first negative culture, native valve endocarditis 4 to 6 weeks, osteomyelitis 6 weeks.

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.

Alternatives. Cefazolin, flucloxacillin, nafcillin; vancomycin or daptomycin for MRSA or severe penicillin allergy.

Contraindications. Penicillin hypersensitivity.

Adverse effects. Hepatitis with raised transaminases, interstitial nephritis, neutropenia with prolonged use, phlebitis, hypokalaemia, rash, Clostridioides difficile infection, anaphylaxis. Comparisons with nafcillin come from observational data and are inconsistent; both agents carry the same major risks.

Interactions. Warfarin (INR changes), methotrexate, probenecid, oral typhoid vaccine. Enzyme induction is less pronounced than with nafcillin but possible.

Common prescribing errors. No liver tests, giving as IV bolus in large doses, and not changing therapy once a safer alternative is possible.

Special groups. - Pregnancy and breastfeeding: acceptable. - Older adults: monitor liver and kidney function. - Kidney impairment: usually no adjustment; reduce in creatinine clearance under 10 mL/min. - Liver impairment: caution and frequent monitoring. - Region: availability is limited in East Africa; flucloxacillin or cloxacillin are used instead.

Preparation. Reconstitute with water for injection. IV: 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. IM use is possible but painful. Extravasation causes tissue injury.

Baseline and monitoring. - Baseline: allergy history, liver tests, creatinine, cultures. - During treatment: liver tests and creatinine twice weekly; full blood count weekly; potassium. - No therapeutic drug monitoring.

Stop rules. Stop for hepatitis, severe rash, neutropenia, or anaphylaxis.

Referral and escalation. Infectious diseases for bacteraemia, endocarditis and bone infection.