cloxacillin

Penicillinase-resistant penicillin· Brands: OrbeninIMIVPO

Mechanism of action

Cloxacillin is a penicillinase-resistant penicillin. It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) on the bacterial cell wall, preventing cross-linking of peptidoglycan. Its resistance to staphylococcal beta-lactamase enables activity against penicillinase-producing staphylococci.

Pharmacokinetics

Cloxacillin is well absorbed from the gastrointestinal tract, although food reduces its rate and extent of absorption. It is widely distributed in body tissues and fluids, but penetration into the CNS is poor. It is highly bound to plasma proteins (approximately 95%) and is metabolised in the liver to a minor extent. The drug is excreted primarily by the kidneys via both glomerular filtration and tubular secretion. The elimination half-life is about 30 minutes in healthy individuals, and it is prolonged in renal impairment.

Indications & dosing

Skin and soft tissue infections

For cellulitis, impetigo, and other skin infections caused by penicillinase-producing staphylococci.

adult · PO: 500 mg every 6 hours · For cellulitis, impetigo, and other skin infections caused by penicillinase-producing staphylococci.

Staphylococcal osteomyelitis

For bone and joint infections due to penicillinase-producing staphylococci.

adult · IV: 1000 mg every 6 hours · For bone and joint infections due to penicillinase-producing staphylococci.

Staphylococcal pneumonia

For pneumonia caused by penicillinase-producing staphylococci.

adult · IV: 1000 mg every 6 hours · For pneumonia caused by penicillinase-producing staphylococci.

Staphylococcal septicaemia

For septicaemia due to penicillinase-producing staphylococci.

adult · IV: 1000 mg every 6 hours · For septicaemia due to penicillinase-producing staphylococci.

Staphylococcal infections in children

Total daily dose of 25-50 mg/kg divided into four equal doses. For children weighing less than 20 kg, use the lower end of range.

pediatric · PO: 25–50 mg/kg/day every 6 hours · Total daily dose of 25-50 mg/kg divided into four equal doses. For children weighing less than 20 kg, use the lower end of range.

Contraindications & precautions

Known hypersensitivity to penicillins or other beta-lactam antibacterials · Includes prior anaphylaxis, bronchospasm, urticaria, or severe skin rash. Cross-reactivity with cephalosporins may occur.
Hypersensitivity to cephalosporins · Consider alternative class if history of severe cephalosporin allergy; mild cross-reactivity may be tolerated with caution.
Assess renal function before use; reduce dose in severe renal impairment to avoid accumulation.
Use with caution in patients with hepatic impairment; monitor liver enzymes during prolonged therapy.
Consider the risk of cross-allergy with cephalosporins, particularly in patients with a history of beta-lactam hypersensitivity.
For oral administration, take on an empty stomach (1 hour before or 2 hours after meals) to optimise absorption.
Monitor for superinfection with prolonged or high-dose therapy; advise patients to report significant diarrhoea.
In severe infections, ensure adequate dosage and consider the need for a parenteral route to achieve therapeutic tissue concentrations.

Adverse effects

Nausea and vomiting
Diarrhoea
Skin rash (maculopapular or urticarial)
Injection site reactions (pain, inflammation, phlebitis)
Clostridioides difficile-associated colitisserious
Cholestatic jaundice / hepatitisserious
Interstitial nephritisserious
Blood dyscrasias (e.g. neutropenia, agranulocytosis, thrombocytopenia)serious
Anaphylaxisserious

Monitoring, pregnancy & toxicity

Liver function tests · At baseline and periodically during prolonged therapy
Renal function · At baseline and periodically, especially in renal impairment or prolonged therapy
Complete blood count · At baseline and periodically during prolonged therapy
Clinical response and signs of hypersensitivity · Throughout treatment
Pregnancy: Cloxacillin is generally considered safe in pregnancy. It has been used extensively without evidence of fetal harm. It may be used when clinically indicated.
Toxicity: Gastrointestinal disturbances, including nausea, vomiting, and diarrhoea · Supportive care with fluid and electrolyte replacement. Discontinue if severe.
Toxicity: Neurotoxicity (e.g., seizures) with high doses or in severe renal impairment · Discontinue cloxacillin and provide supportive treatment. Consider specialist advice.

Clinical notes

Cloxacillin is indicated for infections caused by penicillinase-producing staphylococci, including skin and soft tissue infections, osteomyelitis, septic arthritis, and endocarditis. For serious systemic infections, intravenous administration is recommended; for milder infections, oral therapy may be adequate. Doses should be adjusted in patients with renal impairment, and prolonged use may cause superinfection with resistant organisms. Note that regional formularies may differ; consult local guidelines.

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BNF; local formulary