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[Pharmacology](https://durgical.com/en/pharmacology/) · [Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/)

# Cloxacillin

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

Updated 2026-11-01

- Class: [Beta-lactams](https://durgical.com/en/pharmacology/classes/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](https://www.rcsb.org/structure/8VBU) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/cellulitis-of-the-leg/)
- Staphylococcal osteomyelitis and septic arthritis. [Osteomyelitis →](https://durgical.com/en/conditions/osteomyelitis/)
- Bacteraemia and endocarditis due to methicillin-susceptible S. aureus (intravenous form). [Infective endocarditis →](https://durgical.com/en/conditions/infective-endocarditis/)

## Adverse effects

### Common

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

### Serious (rare, important)

- Anaphylaxis
- Interstitial nephritis
- Bone marrow suppression (rare)
- Clostridioides difficile diarrhoea, from mild to severe colitis

## 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.

## Memory aid

'Isoxazolyl = helmet': a side chain penicillinase cannot crack; against MRSA no helmet helps.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/cloxacillin/)

## Related drugs

- [Dicloxacillin](https://durgical.com/en/pharmacology/dicloxacillin/)
- [Flucloxacillin](https://durgical.com/en/pharmacology/flucloxacillin/)
- [Oxacillin](https://durgical.com/en/pharmacology/oxacillin/)
- [Nafcillin](https://durgical.com/en/pharmacology/nafcillin/)

## Related conditions

- [Cellulitis of the leg](https://durgical.com/en/conditions/cellulitis-of-the-leg/)
- [Osteomyelitis](https://durgical.com/en/conditions/osteomyelitis/)
- [Infective endocarditis](https://durgical.com/en/conditions/infective-endocarditis/)

[← Back to the class: Beta-lactams](https://durgical.com/en/pharmacology/classes/beta-lactams/)

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](https://list.essentialmeds.org/) (World Health Organization, 2025); [RCSB PDB - 8VBU: Structure of the monofunctional Staphylococcus aureus PBP1 in its beta-lactam (Oxacillin) inhibited form](https://www.rcsb.org/structure/8VBU) (RCSB Protein Data Bank, 2026); Farmacología básica y clínica (Katzung), cap. 43 (McGraw Hill, 2025).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

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