flucloxacillin
penicillin antibiotic· Brands: Floxapen, Flucillin, Ladropen, StaphylexIVPO
Mechanism of action
Flucloxacillin is a beta-lactam antibiotic that binds to penicillin-binding proteins (PBPs) on the bacterial cell wall, inhibiting transpeptidase activity and thereby preventing cross-linking of peptidoglycan chains. This leads to inhibition of bacterial cell wall synthesis and ultimately cell lysis. It is resistant to staphylococcal beta-lactamase due to its isoxazolyl side chain, making it effective against penicillinase-producing staphylococci.
Pharmacokinetics
Flucloxacillin is acid-stable and well absorbed after oral administration, with peak plasma concentrations achieved within 1 to 2 hours. It is highly bound to plasma proteins (approximately 95%) and has a volume of distribution of about 0.13 to 0.19 L/kg. It penetrates well into tissues but poorly into the CSF unless the meninges are inflamed. The drug is metabolised to a limited extent in the liver and primarily eliminated unchanged in the urine via tubular secretion. The elimination half-life is approximately 0.5 to 1.1 hours, and clearance is reduced in renal impairment.
Indications & dosing
Skin and soft tissue infections (mild to moderate)
For mild infections such as impetigo, infected eczema, and cellulitis. Use oral route when possible.
- adult · PO: 250–500 mg four times daily · For mild infections such as impetigo, infected eczema, and cellulitis. Use oral route when possible.
Skin and soft tissue infections (severe)
For severe infections, or when oral therapy is not appropriate. Switch to oral therapy as soon as clinically indicated.
- adult · IV: 500–1000 mg four times daily · For severe infections, or when oral therapy is not appropriate. Switch to oral therapy as soon as clinically indicated.
Osteomyelitis
Typically continued for at least 6 weeks. Consider susceptibility to Staphylococcus aureus; not effective against MRSA.
- adult · IV: 2000 mg six hourly · Typically continued for at least 6 weeks. Consider susceptibility to Staphylococcus aureus; not effective against MRSA.
Infective endocarditis
In combination with an aminoglycoside for staphylococcal endocarditis. Duration per local guidelines.
- adult · IV: 2000 mg six hourly · In combination with an aminoglycoside for staphylococcal endocarditis. Duration per local guidelines.
Contraindications & precautions
- Known hypersensitivity to penicillins or other beta-lactam antibiotics · Risk of anaphylaxis; cross-reactivity with other beta-lactams
- Previous flucloxacillin-associated cholestatic hepatitis or jaundice · Recurrence of hepatic injury may be severe
- Severe hepatic impairment · Caution; risk of further liver damage; monitor liver function
- Check for history of penicillin allergy before administration.
- Use with caution in patients with hepatic impairment; monitor liver function, especially during prolonged therapy or high doses.
- Maintain adequate fluid intake to reduce the risk of crystalluria, particularly with high doses.
- Administer on an empty stomach (at least 30 minutes before food) to enhance absorption.
- Monitor for signs of Clostridioides difficile infection if diarrhoea occurs.
- Assess renal function and adjust dose in patients with renal impairment.
Adverse effects
- Nausea and diarrhoea
- Rash
- Cholestatic hepatitisserious
- Anaphylaxisserious
- Clostridioides difficile-associated diarrhoea or colitisserious
- Blood dyscrasias (neutropenia, thrombocytopenia)serious
- Interstitial nephritisserious
Interactions
- warfarinmajorMonitor INR closely before, during, and after co-prescribing flucloxacillin. Consider a reduced warfarin dose or more frequent INR checks, particularly in the first week. Advise patients to report any signs of bleeding. If flucloxacillin is stopped, INR may fall, requiring dose adjustment.
Renal & hepatic adjustment
- eGFR 0–10: Consider reducing the dose or increasing the dosing interval in severe renal impairment (eGFR <10 mL/min); monitor for accumulation.
- Hepatic impairment (severe): No dose adjustment required, but use with caution as flucloxacillin can cause hepatic toxicity.
Monitoring, pregnancy & toxicity
- Liver function tests · Baseline and periodically during prolonged therapy
- Renal function · Baseline and periodic, especially in renal impairment
- Full blood count · If prolonged therapy
- Signs of hypersensitivity · Throughout therapy
- Pregnancy: Flucloxacillin is generally considered safe in pregnancy; use when clinically indicated. No significant risk of fetal harm has been reported.
- Toxicity: Gastrointestinal upset (nausea, vomiting, diarrhoea) · Supportive care, ensure fluid and electrolyte balance.
- Toxicity: Hypersensitivity reactions (rash, pruritus, urticaria) · Discontinue drug and treat with antihistamines or corticosteroids if severe.
- Toxicity: Anaphylaxis · Airway management, epinephrine, corticosteroids.
- Toxicity: Seizures in high doses or renal impairment · Stop drug and give anticonvulsants as needed.
Clinical notes
Flucloxacillin is indicated for the treatment of infections caused by susceptible gram-positive organisms, particularly penicillinase-producing staphylococci. Common indications include skin and soft tissue infections, cellulitis, impetigo, and wound infections. It is also used for osteomyelitis, septic arthritis, and infections in patients with cystic fibrosis. The usual adult dose is 250 to 500 mg orally six-hourly, or 1 to 2 g intravenously four to six-hourly for severe infections. It should be given before meals for optimal absorption. Caution is required in patients with hepatic impairment, as it can be associated with cholestatic jaundice. Common adverse effects include nausea, vomiting, and skin rashes. Serious reactions include anaphylaxis and antibiotic-associated colitis.
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BNF; local formulary