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Penicillinase-Resistant Penicillin (Anti-Staphylococcal)

Flucloxacillin 1–2g IV

Brand names: Floxapen

Adult dose

Dose: Osteomyelitis/septic arthritis: 1–2g IV every 4–6h (up to 8g/day in severe infection). Oral step-down: 1g four times daily (flucloxacillin capsules, 30–60 min before food).
Route: IV or oral
Frequency: Every 4–6h IV; four times daily oral
Max: 8g/day IV (severe infection)
Duration: acute osteomyelitis 4–6 weeks total (IV then oral step-down); septic arthritis 2–4 weeks. Confirm MSSA (methicillin-sensitive Staphylococcus aureus) — if MRSA, use vancomycin or teicoplanin instead. Discuss with microbiology.

Paediatric dose

Dose: 50 mg/kg
Route: IV or oral
Frequency: Every 6h
Max: 2g per dose IV
Concentration: 250 mg/5 mL oral solution mg/ml
Neonates: 25–50 mg/kg every 8–12h. Children: 50 mg/kg every 6h IV (max 2g/dose). Oral: 25 mg/kg four times daily (max 1g/dose). Step-down per local protocol.

Dose adjustments

Renal

No dose adjustment needed in mild-moderate renal impairment; reduce frequency in severe renal failure (eGFR <10)

Hepatic

Caution in severe hepatic impairment — hepatotoxicity risk

Paediatric weight-based calculator

Neonates: 25–50 mg/kg every 8–12h. Children: 50 mg/kg every 6h IV (max 2g/dose). Oral: 25 mg/kg four times daily (max 1g/dose). Step-down per local protocol.

Clinical pearls

  • First-line for MSSA bone and joint infections — covers Staphylococcus aureus (most common organism in haematogenous osteomyelitis)
  • Hepatotoxicity risk: higher with age >55, prolonged courses, female sex — check LFTs at 4 weeks of prolonged therapy
  • IV-to-oral step-down: safe once patient apyrexial, CRP falling, tolerating oral — reduces central line complications and hospital stay
  • Oral flucloxacillin MUST be taken on an empty stomach — food dramatically reduces absorption (bioavailability ~50% with food vs 90% fasting)
  • MRSA suspected: send wound swabs/blood cultures; switch to vancomycin/teicoplanin pending sensitivities

Contraindications

  • Penicillin allergy (including history of anaphylaxis — use clindamycin or vancomycin instead)
  • Previous flucloxacillin-associated hepatotoxicity

Side effects

  • Hepatotoxicity (cholestatic jaundice — may occur weeks to months after stopping)
  • GI upset (nausea, diarrhoea)
  • Rash
  • Hypersensitivity reactions (urticaria, anaphylaxis)
  • Neutropenia (prolonged use)

Interactions

  • Warfarin — increased INR (monitor closely)
  • Methotrexate — reduced renal excretion (increased toxicity)
  • Live vaccines — avoid during active infection treatment

Monitoring

  • LFTs (at 4 weeks of prolonged IV/oral therapy)
  • FBC (neutropenia with prolonged use)
  • CRP and WCC (treatment response)
  • Blood cultures and wound swabs (before first dose)

Reference: BNFc; BNF; Public Health England Osteomyelitis Guidelines; BSAC Bone and Joint Infection Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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