Fusidic Acid

Fusidic acid is a steroid antibiotic with strong activity against Staphylococcus aureus, used orally with a partner drug for staphylococcal bone, joint and skin infection, and topically for localised skin and eye infection. Resistance develops quickly if used alone.

Classification. Fusidane.

Mechanism. Binds elongation factor G and blocks translocation in protein synthesis; bacteriostatic.

Spectrum. Staphylococcus aureus (including MRSA), coagulase-negative staphylococci, Corynebacterium, Clostridium and Neisseria. Moderate activity against streptococci. No activity against Enterobacterales or Pseudomonas.

Pharmacokinetics. Oral bioavailability about 90%. Half-life 10 to 15 hours. Protein binding over 95%. Good bone and joint penetration. Hepatic metabolism with biliary excretion. Strong CYP3A4 and CYP2C8 inhibitor.

Oral maximum 1.5 g daily. Always use with a second active drug for systemic infection.

Adults.

• Oral (sodium fusidate tablets 500 mg): 500 mg every 8 hours, or 750 mg every 12 hours as fusidic acid suspension; combine with rifampicin 300 to 450 mg every 12 hours or with flucloxacillin or other partner.
• Bone and joint infection: 500 mg every 8 hours with rifampicin for 6 weeks or longer, depending on site and response.
• Skin and soft tissue infection: 500 mg every 8 hours with a second active drug for 7 to 10 days.
• Topical cream or ointment 2%: apply thinly two to three times daily for up to 7 days (up to 10 days with review).
• Eye gel 1%: one drop in the conjunctival sac every 12 hours for 7 days.

Children. Oral 15 mg/kg every 8 hours (maximum 500 mg a dose) from 1 month of age; infants under 1 year suspension 15 mg/kg every 8 hours. Topical doses match the adult doses.

Alternatives. Rifampicin plus another active drug, clindamycin, trimethoprim sulfamethoxazole, doxycycline, linezolid; mupirocin or retapamulin (topical).

Contraindications. Hypersensitivity; concurrent statins taken by mouth (simvastatin, atorvastatin, rosuvastatin: avoid during fusidic acid and for 7 days after); severe hepatic impairment; premature or jaundiced neonates.

Adverse effects. Nausea, vomiting, diarrhoea, dyspepsia, rash. Topical: local irritation. Serious: hepatotoxicity (cholestatic, with IV or high doses), jaundice, rhabdomyolysis with statins, thrombophlebitis with IV use, bone marrow suppression (rare), severe skin reactions.

Interactions. Statins (rhabdomyolysis: avoid), ciclosporin and tacrolimus (levels rise), warfarin and direct oral anticoagulants (levels rise), HIV protease inhibitors (levels rise, risk of toxicity), methadone, oral midazolam, QT-prolonging drugs (caution). Rifampicin lowers fusidic acid levels.

Common prescribing errors. Monotherapy, prescribing with statins, use beyond 10 days topically, and use in neonates.

Special groups. - Pregnancy: avoid unless essential. Breastfeeding: acceptable for topical use; avoid oral use if possible. - Older adults: monitor liver tests. - Kidney impairment: no adjustment. - Liver impairment: avoid in severe disease; monitor liver tests in mild to moderate disease. - Region: available as cream in East Africa; oral and IV forms are limited, so topical use is the main role.

Administration. Oral with or after food to reduce nausea. Topical: apply a thin layer to the lesion and wash hands after.

Baseline and monitoring. - Baseline: liver tests, statin and interacting drug review, pregnancy status. - During treatment: liver tests every 2 weeks in oral courses beyond 14 days; muscle symptoms if on interacting drugs.

Stop rules. Stop for jaundice, rising liver enzymes, muscle pain or weakness, or severe rash.

Referral and escalation. Refer for bone and joint infection, treatment failure and hepatotoxicity.