Fusidic acid

Updated: 9.1.22

Introduction

Fusidic acid was discovered in Copenhagen, Denmark and introduced to the clinical practice in the 1960s. It was derived from a fungus, Fusidium coccineum.

Fusidic acid has a structural similarity with the steroid molecule. You can see in the picture the molecular structure is similar to prednisolone. For this reason, it is called a steroid antibiotic.

It also has a structural similarity with cephalosporin P. However, the cephalosporin antibiotics we use are derived from cephalosporin C. Hence fusidic acid is not a cephalosporin.

Mechanism of action

Fusidic acid inhibits protein synthesis by targeting elongation factor G (EF-G).

By binding to the EF-G, it prevents the translocation of t RNA carrying the amino acid on the ribosomal mRNA complex, hence amino acid fails to be incorporated in the growing peptide chain.

Mechanism of resistance

Bacteria can develop resistance to this antibiotic by three mechanisms.

  • Reducing the target affinity, that is, an affinity for the elongation factor G.

  • Enzymatic destruction of the antibiotic and,

  • Efflux pump which helps the bacteria to remove antibiotics from its cell.

The most important resistance mechanism is a mutation in the fus gene, which produces elongation factors with low affinity or protect the EF-G from fusidic acid.

  • fusA – Staph aureus, Staph epidermidis

  • fusB – Staph aureus

  • fusC, fusD – Staph aureus, Staph saprophyticus

  • fusE – Staph aureus (small colony variant)

fusB mutation has been associated with an epidemic impetigo strain.

Other types of mechanisms like enzymatic destruction of acrAB efflux pump can be seen in some gram-negative bacteria.

Properties

  • Oral bioavailability – Suspension and some older preparations 50-70%, while newer film-coated preparation may have IV equivalent bioavailability.

  • Highly protein-bound >95%.

  • Wide distribution in the body; penetrates abscess.

  • Metabolised in liver – Some metabolite are active.

  • The main route of excretion is bile.

Adverse effects

  • Local adverse effects –
    Oral – gastrointestinal disturbances
    IV – thrombophlebitis
    Topical (eye) – dry eye, eye discomfort, conjunctivitis.

  • Gastro-hepatic – hyperbilirubinaemia, decreased appetite.

  • CNS – dizziness, headache,

  • Haematological – anaemia, leukopenia, thrombocytopenia.

  • Skin – rash, Toxic epidermal necrolysis, Stevens-Johnson syndrome, DRESS syndrome.

  • Muscle – Rhabdomyolysis (avoid using concurrently with statins).

Spectrum

  • Fusidic acid is mainly used for Staphylococcus infection. It has activity against Staphylococcus aureus including MRSA. Some coagulase negative Staphylococcus are also susceptible.

  • Streptococcus are less susceptible and Enterococcus are often resistant.

  • Fusidic acid has activity against Corynebacterium spp, and some Mycobacteria.

  • t is mostly resistant to gram-negative bacteria. However, it retains some activity against Neisseria, Moraxella, Legionella etc.

  • It has a good anti-anaerobe spectrum and is active against C difficile. However, Fusobacterium and some anaerobes tend to have high MIC.

Indication

  • Staphylococcal skin infection – Non-bullous impetigo, bacterial superinfection

  • Staphylococcal eye infection

  • Deep staphylococcal infection – osteomyelitis, endocarditis.

Systemic monotherapy is not recommended as resistance may develop quickly.