Fusidic acid, sold under the brand name Fucidin among others, is an antibiotic that is often used topically in creams or ointments and eyedrops but may also be given systemically as tablets or injections. , the global problem of advancing antimicrobial resistance has led to a renewed interest in its use.
Medical uses
Fusidic acid is active
in vitro against
Staphylococcus aureus,
most coagulase-positive 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 against
Mycobacterium tuberculosis.
One use of fusidic acid is its activity against methicillin-resistant Staphylococcus aureus (MRSA).
Topical fusidic acid is occasionally used as a treatment for acne vulgaris.
Side effects
Fucidin tablets and suspension, whose active ingredient is sodium fusidate, occasionally cause liver damage, which can produce jaundice (yellowing of the skin and the whites of the eyes). This condition will almost always get better after the patient finishes taking Fucidin tablets or suspension. Other related side-effects include dark urine and lighter-than-usual feces. These, too, should normalize when the course of treatment is completed.
Pharmacology
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,
Streptococcus and
Corynebacterium species.
Fusidic acid is a tetracyclic, naturally occurring steroid derived from the fungus Fusidium coccineum. It was first isolated in 1960 and developed by Leo Pharma in Ballerup, being used clinically from 1962 onwards.
Mechanism of action
Fusidic acid binds to EF-G after translocation and GTP (guanosine-5'-triphosphate) hydrolysis.
This interaction prevents the necessary conformational changes for EF-G release from the ribosome, effectively blocking the protein synthesis process. Fusidic acid can only bind to EF-G in the ribosome after GTP hydrolysis.
Since translocation is a part of elongation and ribosome recycling, fusidic acid can block either or both steps of protein synthesis.
Dose
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.
The use of topical preparations (skin creams and eye ointments) containing fusidic acid is strongly associated with the development of resistance,
and there are voices advocating against the continued use of fusidic acid monotherapy in the community.
Topical preparations used in Europe often contain fusidic acid and
gentamicin in combination, which helps to prevent the development of resistance.
Cautions
There is inadequate evidence of safety in human pregnancy. Animal studies and many years of clinical experience suggest that fusidic acid is devoid of
Teratology (birth defects), but fusidic acid can cross the placental barrier.
Resistance
In vitro susceptibility studies of US strains of several bacterial species such as
S. aureus, including MRSA and coagulase negative
Staphylococcus, indicate potent activity against these pathogens.
[Castanheira M, Mendes RE, Rhomberg PR and Jones RN (2010). Activity of fusidic acid tested against contemporary Staphylococcus aureus collected from United States hospitals. Infectious Diseases Society of America, 48th Annual Meeting, Abstract 226.]
Mechanisms of resistance have been extensively studied only in Staphylococcus aureus. The most studied mechanism is the development of point mutations in fusA, the chromosomal gene that codes for EF-G. The mutation alters EF-G so that fusidic acid is no longer able to bind to it.
Some bacteria also display 'FusB-type' resistance, which has been found to be the most prevalent in Staphylococcus spp. in many clinical isolates.
Interactions
Fusidic acid should not be used with quinolone antibiotics, with which it is antagonistic. Although clinical practice over the past decade has supported the combination of fusidic acid and
rifampicin, a recent clinical trial showed that there is an antagonistic interaction when both antibiotics are combined.
On 8 August 2008, it was reported that the Irish Medicines Board was investigating the death of a 59-year-old Irish man who developed rhabdomyolysis after combining atorvastatin and fusidic acid, and three similar cases.
Society and culture
Brand names and preparations
-
Fucidin (of Leo in Canada)
-
Fucidin H (topical cream with hydrocortisone - Leo)
-
Fucidin (of Leo in UK/ Leo-Ranbaxy-Croslands in India)
-
Fuci-Ophthalmic (As eye gel in Damascus, Syria)
-
Fucidine (of Leo in France, Germany and Spain)
-
Fusicutan Creme (topical cream in Germany)
-
Fucidin (of Leo in Norway and Israel)
-
Fucidin (of Adcock Ingram, licensed from Leo, in South Africa)
-
Fucithalmic (of Leo in the UK, the Netherlands, Denmark and Portugal)
-
Fucicort (topical mixture with hydrocortisone)
-
Fucibet (fusidic acid/betamethasone valerate topical cream)
-
Ezaderm (topical mixture with betamethasone)(of United Pharmaceutical "UPM" in Jordan)
-
Fuci (of pharopharm in Egypt)
-
Fucizon (topical mixture with hydrocortisone of pharopharm in Egypt)
-
Foban (topical cream in New Zealand)
-
Betafusin (fusidic acid/betamethasone valerate topical cream in Greece)
-
Betafucin (2% fusidic acid/1% betamethasone valerate topical cream in Egypt)(of Delta Pharma S.A.E., A.R.E. (Egypt))
-
Fusimax (of Roussette in India)
-
Fusiderm (topical cream and ointment by Indi Pharma in India)
-
Fusid (in Nepal)
-
Fudic (topical cream in India)
-
Tosidic (2% fusidic acid cream), of T.O.CHEMICALS (1979) in Thailand
-
Fucidin (후시딘, of Donghwa Pharm in South Korea)
-
Dermy (Topical cream of W. Woodwards in Pakistan)
-
Fugen Cream (膚即淨軟膏 in Taiwan)
-
Phudicin Cream (in China; 夫西地酸
-
Fucidin Fusidic Acid (in China;夫西地酸 of Leo Laoratories Limited)
-
Dermofucin cream, ointment and gel (in Jordan)
-
Optifucin viscous eye drops (of API in Jordan)
-
Verutex (of Roche in Brazil)
-
Taksta (of Cempra in U.S. For export only in US)
-
Futasole (of Julphar in Gulf and north Africa)
-
Stanicid (2% ointment of Hemofarm in Serbia)
-
Staphiderm Cream (Israel By Trima).
-
Fuzidin (tablets of Biosintez in Russia)
-
Fuzimet (ointment with methyluracil of Biosintez in Russia)
-
Axcel Fusidic Acid (2% cream and ointment of Kotra Pharma, Malaysia)
-
Ofusidic (eye drops produced by Orchidia pharmaceutical in Egypt
Research
An orally administered mono-therapy with a high loading dose is under development in the United States.
A different oral dosing regimen, based on the compound's pharmacokinetic/pharmacodynamic (PK-PD) profile is in clinical development in the US.[Moriarty SR, Clark K, Scott D, Degenhardt TP, Fernandes P, Craft JC, Corey GR, Still JG and Das A (2010). 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Abstract L1-1762] as Taksta.
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.
Biosynthesis
The biosynthetic machinery in
Fusidium coccineum (also known as
Acremonium fusidioides) has been sequenced and analyzed. (3S)-2,3-oxidosqualene and
fusidane are two intermediates.
External links
