Oxacillin !

An intravenous penicillinase-resistant penicillin for serious infections by methicillin-susceptible Staphylococcus aureus.

Updated 2026-11-01

Class: Beta-lactams
Enzyme: Penicillin-binding proteins (bacterial transpeptidases)
ATC code: J01CF04

Penicillin-binding proteins (bacterial transpeptidases)Oxacillin

The figure shows Staphylococcus aureus PBP1 inhibited by oxacillin, bonded to the active-site serine.

Target in 3D: Penicillin-binding proteins (bacterial transpeptidases). PDB structure 8VBU (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Oxacillin is a parenteral isoxazolyl penicillin. It belongs to the penicillins resistant to staphylococcal β-lactamase: its bulky side chain keeps penicillinase from opening the β-lactam ring, so it acylates the PBPs of penicillinase-producing staphylococci. It does not work against MRSA, whose PBP2a has low affinity for β-lactams.

Staphylococcal penicillinase cannot open its ring
Acylates the staphylococcal PBPs
Peptidoglycan cross-linking stops
The staphylococcus lyses

Pharmacokinetics

Absorption: Intravenous or intramuscular.
Elimination: By the kidney and by liver inactivation and bile; usually no adjustment in kidney failure.
Half-life: Short, under one hour.

Indications

Skin and soft-tissue infections due to penicillinase-producing staphylococci. Cellulitis of the leg →
Staphylococcal osteomyelitis and septic arthritis. Osteomyelitis →
Bacteraemia and endocarditis due to methicillin-susceptible S. aureus. Infective endocarditis →

Adverse effects

Common

Phlebitis at the infusion site
Rash, fever
Raised transaminases

Contraindications

History of a hypersensitivity reaction to any penicillin
Dextrose-containing solutions may be contraindicated with corn allergy

Key interactions

Tetracyclines: Bacteriostatic: they can antagonise the bactericidal effect; the combination is avoided.
Probenecid: Reduces tubular secretion: higher and longer-lasting β-lactam levels.

What is monitored

Periodic kidney and liver function and blood count in long courses
Cultures and susceptibility

Administration and safety

Intravenous; premixed bags are for intravenous use only.
Do not confuse oxacillin with other similarly named antistaphylococcal penicillins.

Nursing care

Before the first dose: ask about allergy to penicillins, cephalosporins and other β-lactams, and what the reaction was.
Watch for fever, rash, urine changes and creatinine (interstitial nephritis).
Check the IV site for phlebitis.
Teach the patient to report watery or bloody diarrhoea, even weeks after the course ends.

Pregnancy and breastfeeding

Animal studies showed no fetal harm and there are no controlled studies in pregnant women; used if clearly needed.

Test yourself

Think of the answer, then tap the question to see it.

Why does oxacillin not work against MRSA?

Because MRSA carries PBP2a, a PBP with low affinity for β-lactams.

Which kidney toxicity is linked to oxacillin?

Tubular damage and interstitial nephritis, both uncommon.

Does oxacillin need adjustment in kidney failure?

Generally not, because it is also cleared by the liver and bile.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Oxacillin Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - OXACILLIN injection, solution (DailyMed (U.S. National Library of Medicine), 2026); RCSB PDB - 8VBU: Structure of the monofunctional Staphylococcus aureus PBP1 in its beta-lactam (Oxacillin) inhibited form (RCSB Protein Data Bank, 2026); Farmacología básica y clínica (Katzung), cap. 43 (McGraw Hill, 2025).

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Representative model, for educational purposes only.