Fusidic acid

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Fusidic acid
Fusid Wiki str.png
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PubChem CID
E number{{#property:P628}}
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Chemical and physical data
FormulaC31H48O6
Molar mass516.709

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Fusidic acid is a bacteriostatic antibiotic that is often used topically in creams and eyedrops, but may also be given systemically as tablets or injections.

Pharmacology

Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. Fusidic acid is only effective on gram-positive bacteria such as Staphylococcus species 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 in Ballerup, Denmark and released for clinical use in the 1960s. It has also been isolated from Mucor ramannianus and Isaria kogana. The drug is not licensed for use in the US, but, as sodium fusidate, it is approved for use under prescription in the UK, Europe Australia and New Zealand.

Uses

Fusidic acid is active in vitro against Staphylococcus aureus, most coagulase-negative staphylococci, Corynebacterium species, most clostridium species. Fusidic acid has no useful activity against streptococci, 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.

The most important use of fusidic acid clinically is its activity against Methicillin Resistant Staphylococcus Aureus, a sometimes-fatal 'hospital-acquired 'superbug'.[1] Many strains of MRSA remain sensitive to fusidic acid, but because there is a low genetic barrier to resistance (a single point mutation is all that is required), fusidic acid must never be used on its own to treat MRSA and should be combined with another antimicrobial such as rifampicin.

Fusidic acid is often found in topical skin and eye preparations (e.g., Fusibet®), a use which has been contested.[2]

Dosing

Fusidic acid should not be used on its own to treat Staph. aureus infections. The use of topical preparations (skin creams and eye ointments) containing fusidic acid is strongly associated with the development of resistance,[3] and there are voicing agitating against the continued use of fusidic acid monotherapy in the community.[2] 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.[4] 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, including endocarditis (infection of the heart chambers).

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)...fusidic acid can cross the placental barrier.[5]

Side Effects

  • 'Fucidin®) Tablets and Suspension can occasionally cause liver upsets which can produce jaundice (yellowing of a patient's skin and the whites of his or her eyes). This condition will almost always get better after you finish taking Fucidin®) Tablets or Suspension.

Other related side effects include dark urine, lighter-than-usual feces. These, too should normalize when the course of treatment is completed.'[6]

  • Patients taking the drug should tell their doctors if they notice that their urine is 'very dark', their feces is 'very pale' or if their skin or the whites of their eyes becomes yellow, the Australian data sheet for patients adds.

Resistance

Because the drug is not licensed for use in the US, and there are therefore no Clinical and Laboratory Standards Institute standard definitions of fusidic acid resistance.

In the UK and Australia, susceptibility is defined as an MIC of 0.25mg/l or 0.5mg/l or less. Resistance is defined as an MIC of 2mg/l or more. In laboratories using disc diffusion methods, susceptibility for a 2.5µg disc is defined as a zone of 22 mm or more, and resistance is defined as a zone of 17 mm or less; intermediate values are defined as intermediate resistance.

Mechanisms of resistance have only been extensively studied in Staphylococcus aureus. The most important mechanism is the development of point mutations in fusA, the chromosomal gene which codes for EF-G. The mutation alters EF-G so that fusidic acid is no longer able to bind to it.[7][8] Resistance is readily acquired when fusidic acid is used alone and commonly develops during the course of treatment, but resistance does not occur when fusidic acid is used in combination with other antibiotics.[9] For this reason, fusidic acid should not be used on its own to treat Staph. aureus infections.


Some bacteria also mediate resistance via the fusB gene, which is carried on a plasmid; the mechanism by which fusB causes resistance is unknown.

Interactions

Fusidic acid must not be used with quinolones, with which they are antagonistic. When combined with rifampicin, the action of fusidic acid is additive or synergistic.[10]


It is delivered as an ointment, a cream, eye drops or in tablet form.

Trade names and preparations

  • Fusidin (of Leo in Canada)
  • Fucidin (of Leo in UK/ Leo-Ranbaxy-Croslands in India)
  • Fucidine (of Leo in France)
  • Fucithalmic (of Leo in UK and Denmark)
  • Fucicort (topical mixture with hydrocortisone)
  • Fucibet (topical mixture with betamethasone)

References

  1. Existing drug will cure hospital superbug MRSA, say scientists – The Guardian, 17 January 2007.Accessed 2007-09-09.
  2. 2.0 2.1 Howden BP, Grayson ML. "Dumb and dumber—the potential waste of a useful antistaphylococcal agent: emerging fusidic acid resistance in Staphylococcus aureus". Clin Infect Dis. 42 (3): 394&ndash, 400.
  3. Mason BW, Howard AJ, Magee JT (2003). "Fusidic acid resistance in community isolates of methicillin-susceptible Staphylococcus aureus and fusidic acid prescribing". J Antimicrob Chemother. 51: 300&ndash, 3.
  4. Fucidin data sheet archived by New Zealand government. December 2005.Accessed: 2007-09-09.
  5. Fucidin®) UK data sheet archived at the electronic Medicines Compendium. June 1997.Accessed: 2007-09-09.
  6. Fucidin®) patient information leaflet, archived by Government of Victoira, Australia.Accessed: 2007-09-09.
  7. Turnidge J, Collignon P (1999). "Resistance to fusidic acid". Int J Antimicrob Agents. 12 (Suppl 2): S35&ndash, 44.
  8. Besier S, Ludwig A, Brade V, Wichelhaus TA (2003). "Molecular analysis of fusidic acid resistance in Staphylococcus aureus". Mol Microbiol. 47: 463&ndash, 9.
  9. Fantin B, Leclerq R, Duval J, Carbon C (1993). "Fusidic acid alone or in combination with vancomycin for therapy of experimental endocarditis due to methicillin-resistant Staphylococcus aureus". Antimicrob Agents Chemother. 37: 2466&ndash, 69.
  10. Collignon P, Turnidge J (1999). "Fusidic acid in vitro activity". Int J Antimicrob. 12 (Suppl 2): S45&ndash, 58.


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