Fusidic acid acts as a bacterial protein synthesis inhibitor by preventing the turnover of elongation factor G (EF-G) from the ribosome. Fusidic acid is effective primarily on gram-positive bacteria such as Staphylococcus species,Streptococcus species, ^[2] and Corynebacterium species. Fusidic acid inhibits bacterial replication and does not kill the bacteria, and is therefore termed bacteriostatic.

Fusidic acid is a true antibiotic, derived from the fungus Fusidium coccineum and was developed by Leo Laboratories inBallerup, Denmark and released for clinical use in the 1960s. It has also been isolated from Mucor ramannianus andIsaria kogana. The drug is licensed for use as its sodium salt sodium fusidate, and it is approved for use under prescription in South Korea, Japan, UK, Canada, Europe, Australia, New Zealand, Thailand, India and Taiwan. A different oral dosing regimen, based on the compound's Pharmacokinetic/pharmacodynamic (PK-PD) profile is in clinical development in the U.S.^[3] as Taksta.

Uses

Fusidic acid is active in vitro against Staphylococcus aureus, most coagulase-negative staphylococci, Beta-hemolytic streptococci, Corynebacterium species, and most clostridium species. Fusidic acid has no known useful activity against enterococci or most Gram-negative bacteria (except Neisseria, Moraxella, Legionella pneumophila, and Bacteroides fragilis). Fusidic acid is active in vitro and clinically against Mycobacterium leprae but has only marginal activity againstMycobacterium tuberculosis.

One important clinical use of fusidic acid is its activity against methicillin-resistant Staphylococcus aureus.^[4] Many strains of MRSA remain sensitive to fusidic acid, but, because there is a low genetic barrier to drug resistance (a single point mutation is all that is required), fusidic acid must never be used on its own to treat serious MRSA infection and should be combined with another antimicrobial such as rifampicin when administering oral or topical dosing regimens approved in Europe, Canada, and elsewhere. However, resistance selection is low when pathogens are challenged at high drug exposure.^[5] An orally-administered mono-therapy with a high loading dose is under development in the United States.^[3]

Topical fusidic acid is occasionally used as a treatment for acne vulgaris.^[6] As a treatment for acne, fusidic acid is often partially effective at improving acne symptoms.^[7] However, research studies have indicated that fusidic acid is not as highly active against Propionibacterium acnes as many other antibiotics that are commonly used as acne treatments.^[8]Fusidic acid is also found in several additional topical skin and eye preparations (e.g. Fucibet), although its use for these purposes is controversial.^[9]

Fusidic acid is being tested for indications beyond skin infections. There is evidence from compassionate use cases that fusidic acid may be effective in the treatment of patients with prosthetic joint-related chronic osteomyelitis.^[10]

[edit]Dosing

Fusidic acid should not be used on its own to treat S. aureus infections when used at low drug dosages. However, it may be possible to use fusidic acid as monotherapy when used at higher doses.^[3] The use of topical preparations (skin creams and eye ointments) containing fusidic acid is strongly associated with the development of resistance,^[11] and there are voices agitating against the continued use of fusidic acid monotherapy in the community.^[9] Topical preparations used in Europe often contain fusidic acid and gentamicin in combination, which helps to prevent the development of resistance.

Depending on the reason for which sodium fusidate is prescribed, the adult dose can be 250 mg twice a day and or up to 750 mg three times a day. (Skin conditions normally need the smaller dose). It is available in tablet and suspension form.^[12] A front-loading oral dosing regimen is in clinical development in the U.S. based on the pharmacokinetic/pharmacodynamic profile of the compound. It incorporates a dose of 1,500 mg twice on the first day followed by 600 mg twice-daily. It has been demonstrated in an in vitro model to have a low potential for selection of resistant organisms.^[3]

There is an intravenous preparation available, but it is irritant to veins, causing phlebitis. Most people absorb the drug extremely well after taking it orally, so, if a patient can swallow, there is not much need to administer it intravenously, even if used to treat endocarditis (infection of the heart chambers).

[edit]Pregnancy caution

There is inadequate evidence of safety in human pregnancy. Animal studies and many years of clinical experience suggest that fusidic acid is devoid of teratogenic effects (birth defects), but fusidic acid can cross the placental barrier.^[13]