Flucloxacillin !

A penicillinase-resistant penicillin, oral or injected, for staphylococcal skin, wound and bone infections; it rarely injures the liver.

Updated 2026-11-01

Class: Beta-lactams
Enzyme: Penicillin-binding proteins (bacterial transpeptidases)
ATC code: J01CF05

Penicillin-binding proteins (bacterial transpeptidases)Flucloxacillin

The figure shows oxacillin, an isoxazolyl penicillin of the same group, in Staphylococcus aureus PBP1; no structure of this drug 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

Flucloxacillin is an isoxazolyl penicillin, a relative of cloxacillin. 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. Its hypersensitivity liver injury has been linked to the HLA-B*57:01 allele.

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

Pharmacokinetics

Absorption: Oral or injected; the oral form is taken on an empty stomach.

Indications

Skin and wound infections. Cellulitis of the leg →
Bone infections (osteomyelitis). Osteomyelitis →
Ear infections.

Adverse effects

Common

Nausea, vomiting, diarrhoea
Bloating and indigestion

Contraindications

History of a hypersensitivity reaction to any penicillin
Liver or kidney disease: needs assessment before use

Key interactions

Methotrexate: May raise its toxicity.
Warfarin: May alter the INR; it is monitored.
Probenecid: Reduces tubular secretion: higher and longer-lasting β-lactam levels.
Oral typhoid vaccine: Flucloxacillin can make it less effective.

What is monitored

Signs of liver injury: jaundice, dark urine, pale stools
Liver function in patients with prior liver disease

Administration and safety

The oral form is taken at least one hour before eating or two hours after.
Do not confuse flucloxacillin with cloxacillin or dicloxacillin.

Nursing care

Before the first dose: ask about allergy to penicillins, cephalosporins and other β-lactams, and what the reaction was.
Teach the patient to recognise jaundice, dark urine or pale stools, also up to two months afterwards.
Ask about prior liver or kidney disease.
Teach the patient to report watery or bloody diarrhoea, even weeks after the course ends.

Pregnancy and breastfeeding

It can be used in pregnancy and breastfeeding; little passes into breast milk.

Test yourself

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

Which serious adverse effect characterises flucloxacillin?

Liver injury with jaundice, which may appear up to weeks after the course ends.

Which HLA allele has been linked to flucloxacillin liver toxicity?

HLA-B*57:01, the same allele linked to abacavir hypersensitivity.

Does flucloxacillin work for MRSA?

No; like the other isoxazolyl penicillins, it cannot overcome PBP2a.

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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: Flucloxacillin: an antibiotic medicine to treat infections - NHS (NHS (National Health Service, UK), 2025); Farmacología básica y clínica (Katzung), cap. 5 (McGraw Hill, 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.