Fusidic acid is a topical antibiotic used in cream and eye drops but can also be given systemically such as tablets or injections. The global problem of advancing antimicrobial resistance has led to renewed interest in its recent use.
Video Fusidic acid
Pharmacology
Fusidic acid acts as a bacterial protein synthesis inhibitor by preventing the replacement of G (EF-G) elongation factor of the ribosome. Fusidic acid is particularly effective in Gram-positive bacteria such as Staphylococcus species, Streptococcus species , and Corynebacterium . Fusidic acid inhibits bacterial translations and does not kill bacteria, and is therefore called "bacteriostatic".
Fusidic acid is a steroid antibiotic, derived from the fungus Fusidium coccineum and developed by Leo Pharma 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 licensed for use as sodium salt sodium fusidate , and is approved for use under recipes in South Korea, Japan, UK, Canada, Europe, Australia, New Zealand, Thailand, India and Taiwan.. Different oral dosing regimens, based on pharmacokinetic/pharmacodynamic (PK-PD) profiles of these compounds in clinical development in the US as Taksta.
Maps Fusidic acid
Usage
Fusinate active acid in vitro against Staphylococcus aureus , positive coagulase-positive staphylococci, Beta-hemolytic streptococcus, Corynebacterium species , and most clostridium species. Fusidic acid has no beneficial activity against the 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 important clinical use of fusidic acid is its activity against methicillin-resistant Staphylococcus aureus (MRSA). Although many MRSA strains remain sensitive to fusidic acid, there is a low genetic barrier to drug resistance (one point mutation is all that is required), fusidic acid should not be used alone to treat serious MRSA infections and should be combined with other antimicrobials such as rifampicin when administered approved oral dose or topical regimens in Europe, Canada and elsewhere. However, selection of resistance is low when pathogens are challenged in high drug exposure. Oral monotherapy therapy with high loading doses is being developed in the United States.
Topical fusidic acid is sometimes used as a treatment for acne vulgaris. As a treatment for acne, fusidic acid is often effective in improving the symptoms of acne. However, studies show that fusidic acid is less active against Propionibacterium acnes because many other antibiotics are commonly used as acne treatments. Fusidic acid is also found in some supplemental skin and topical eye preparations (eg Fucibet), although its use for this purpose is controversial.
Fusidic acid is being tested for indications beyond skin infections. There is evidence of a compassionate use case that fusid acid may be effective in treating patients with chronic osteomyelitis associated prosthetic joints.
Dose
Fusidic acid should not be used alone to treat an infection S. aureus when used at low doses of the drug. However, it is 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 sounds that support 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 prevent resistance development.
Depending on the reason that sodium fusidate is prescribed, the adult dose may be 250 mg twice daily and or up to 750 mg three times daily. (Skin conditions usually require smaller doses). It is available in tablet and suspension form. An oral dose regimen is in clinical development in the US based on the pharmacokinetic/pharmacodynamic profile of the compound. It combines a dose of 1,500 mg twice on the first day followed by 600 mg twice daily. It has been demonstrated in the in vitro model to have a low potential for selection of resistant organisms.
There is available intravenous preparation, but it irritates the blood vessels, causing phlebitis. Most people take this medicine very well after taking it orally, so, if a patient can swallow, not much should be given intravenously, even if used to treat endocarditis (infection of the heart chambers).
Caution
There is no evidence of adequate safety in human pregnancy. Animal studies and many years of clinical experience suggest that fusidic acid does not contain teratogenic effects (birth defects), but fusidic acid may cross the placental barrier.
Side effects
Tablets and suspensions of Fucidin, whose active ingredient is sodium fusidate, sometimes cause liver disorders, which can cause jaundice (the skin becomes yellow and white of the eye). This condition almost always improves after the patient has finished taking Fucidin tablets or suspensions. Other related side effects include dark urine and lighter feces than usual. It should also normalize when treatment is complete. Patients taking the drug should tell their doctor if they see any of these side effects.
Resistance
Studies of in vitro susceptibility of US strains of several species of bacteria such as S. aureus , including MRSA and negative coagulase Staphylococcus , show a potent activity against these pathogens
In the UK and Australia, susceptibility is defined as a minimum inhibitory concentration (MIC) of 0.25 mg/l or 0.5 mg/l or less. Resistance is defined as a MIC of 2 mg/l or more. In the laboratory using the disc diffusion method, the vulnerability for 2.5 Âμg disks is defined as a zone of 22 mm or more, and resistance is defined as a 17 mm or less zone; the intermediate value is defined as the intermediate resistance. This vulnerability criterion is based on a lower dose regimen used outside the US. Clinical trials in the US combine different dosing regimens that produce higher blood levels. Therefore, a US dosing regimen may warrant different vulnerability criteria.
The mechanism of resistance has been studied extensively only in Staphylococcus aureus . The most important mechanism is the development of point mutations in fusA , the chromosome gene encoding EF-G. Mutations change EF-G so that fusidic acid can no longer bind it. Resistance is easily obtained when fusidic acid is used alone and generally develops during treatment. Like most other antibiotics, resistance to fusidic acid occurs less frequently when used in combination with other drugs. For this reason, fusidic acid should not be used by itself to treat serious Staph. aureus infection. However, at least in Canadian hospitals, data collected between 1999-2005 showed low levels of resistance from MSSA and MRSA to fusidic acid, and mupirocin was found to be a more problematic topical antibiotic for the aforementioned conditions.
Some bacteria also feature a 'fusB-type' resistance. This resistance mechanism is mediated by fusB, fusC, and fusD genes found in plasmids. The fusB type resistance gene product is a residual cytoplasm protein 213 that interacts in a 1: 1 ratio with EF-G. Fus-type proteins bind in different areas of fusidic acid to induce conformational changes resulting in EF-G release of fusidic acid, allowing an extension factor to participate in another round of ribosomal translocation.
FusB-type resistance is common in clinical MRSA isolates and is observed in more than 70% of some cohorts
Interactions
Fusidic acid should not be used with quinolones, with which they are antagonists. When combined with rifampicin, the action of fusidic acid is additive or synergistic It was reported on August 8, 2008, that the Irish Drug Board is investigating the death of a 59-year-old Irish man who developed rhabdomyolysis after combining atorvastatin and Fusidic Acid, and three similar cases. In August 2011, the British Drug and Healthcare Regulatory Body issued a Drug Safety Update warning that "Systemic Fusidic Acid (Fucidin) should not be administered with statins because of the risk of serious and potentially fatal rhabdomyolysis."
It is delivered as an ointment, such as cream, eye drops, or in tablet form.
Name and preparation of merchandise
References
External links
- Fusidic acid is bound to proteins in GDP
Source of the article : Wikipedia
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