Cloxacillin !

A penicillinase-resistant antistaphylococcal penicillin for infections due to methicillin-susceptible Staphylococcus aureus.

Updated 2026-11-01

Class: Beta-lactams
Enzyme: Penicillin-binding proteins (bacterial transpeptidases)
ATC code: J01CF02
WHO Model List of Essential Medicines

Penicillin-binding proteins (bacterial transpeptidases)Cloxacillin

The figure shows oxacillin, an isoxazolyl penicillin of the same group, in Staphylococcus aureus PBP1; no structure of cloxacillin bound to a PBP has been published.

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

Mechanism of action

Cloxacillin is an isoxazolyl penicillin: its bulky side chain keeps staphylococcal penicillinase away from 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. It is cleared by the kidney and in bile.

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

Pharmacokinetics

Absorption: Oral or parenteral; food impairs absorption of oral penicillins.
Distribution: High protein binding: a smaller free fraction than other penicillins.
Elimination: By renal and biliary excretion; usually no adjustment is needed in kidney failure.

Indications

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

Adverse effects

Common

Nausea, diarrhoea
Rash, fever, eosinophilia
Phlebitis with the intravenous form

Contraindications

History of a hypersensitivity reaction to any penicillin

Key interactions

Tetracyclines and chloramphenicol: Bacteriostatic drugs can antagonise the bactericidal effect.

What is monitored

Blood count, kidney and liver function in long courses
Cultures and susceptibility (rule out MRSA)

Administration and safety

The oral form is given away from meals.
Do not confuse cloxacillin with dicloxacillin, flucloxacillin or oxacillin: they are relatives, but presentations and routes differ.

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 or urine changes in long courses (interstitial nephritis).
Teach the patient to report watery or bloody diarrhoea, even weeks after the course ends.

Pregnancy and breastfeeding

Penicillins are widely used in pregnancy without a known rise in birth defects.

Test yourself

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

Why does cloxacillin resist staphylococcal penicillinase?

Its bulky isoxazolyl side chain keeps the enzyme from reaching the β-lactam ring.

Does cloxacillin work against MRSA?

No; MRSA's resistance comes from PBP2a, which does not bind cloxacillin.

Does cloxacillin need adjustment in kidney failure?

Generally not: it is cleared both by the kidney and in 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: eEML - Electronic Essential Medicines List (World Health Organization, 2025); 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.